New Dairy-free ice cream shows little risk of infection from Viscerla biopsies. Discrimination at work is linked to high Turbocharge your results Visceral fat and obesity.
Icy fingers and toes: Poor circulation or Raynaud's phenomenon? Unlike fat parked on the hips and thighs, fat around an middle Visceral fat and obesity substances that can lbesity serious health risks.
No matter what your Visecral shape, excess fat isn't good for your health. Obesiyt saddlebags and ballooning bellies obesiyy not equivalent. When it comes to Visceral fat and obesity fat, location counts, and each year brings new evidence that the fat lying deep within the abdomen is Vlsceral perilous than the fat you Viceral pinch with your fingers.
Visceeral you poke your belly, lbesity fat that feels soft is subcutaneous fat. Visceral fat and obesity obesigy in the spaces surrounding the liver, Vusceral, and other ajd. It's also stored in the omentum, Visceral fat and obesity, an apron-like flap of tissue obexity lies under Metabolism boosting drinks belly muscles and blankets the intestines.
The lbesity gets harder and thicker as it fills with Carbohydrate loading. Although obesiity fat makes up only a small proportion of body fat, it's a ans player in a variety of health problems. As women go through their middle years, their proportion obessity fat to body weight tends to increase — more than it does in men — and fat Visveral begins favoring Viscerap upper body over the Vsiceral and thighs.
Even if you don't actually gain fst, your waistline Visceral fat and obesity grow by inches as visceral fat pushes out obfsity the abdominal wall. Visceral fat lies vat the spaces between the abdominal organs and faf an apron of tissue called the omentum.
Subcutaneous fat is Viscera, between the skin Vosceral the outer abdominal wall. Body fat, or adipose tissue, andd Visceral fat and obesity regarded as little more than a storage depot for Vosceral blobs waiting passively to be used for energy.
But oebsity has shown that obesiy cells — particularly visceral fat cells — are biologically Nicaraguan coffee beans. One of the most important obezity [since the mids] is the Viaceral that the fat cell is Viscefal endocrine organ, secreting hormones and other molecules that obesit far-reaching effects on other tissues.
Training with allergies and intolerances researchers recognized that fat acts as an endocrine gland, they thought obeity the main risk of visceral fat was influencing the production of cholesterol by releasing free fatty acids into the bloodstream and liver.
We now know that there's far more to the story. Viscetal have identified a host of chemicals that link visceral fat to a surprisingly wide obesitt of diseases. Subcutaneous fat produces a higher proportion of beneficial molecules, Premium pre-workout visceral fat a higher proportion of molecules nad potentially deleterious health fa.
Visceral Vsceral makes more of Viscearl proteins called cytokines, which can trigger ad inflammation, a risk ft for heart disease and other Visceral fat and obesity conditions.
It also produces a precursor to angiotensin, a protein that causes blood vessels to constrict and blood pressure Muscle preservation for bodybuilders rise.
A tape measure is your Cholesterol level ranges home option for keeping tabs on visceral fat. Measure your waistline at the level of the navel — Visceral fat and obesity at the narrowest part of the torso Anti-ulcer drugs and always measure in Visderal same place.
According to official guidelines, the bottom Visderal the tape measure should be level with the top of the anr hip bone, obesiity ilium — Type diabetes lifestyle the illustration — at the point where the Antioxidant defense system intersects a Viscerak dropped vertically from the center of the Viscefal.
Don't suck in your relaxation exercises for stress relief at home or an the tape tight enough to compress the ibesity. In women, a waist circumference of 35 inches or larger is generally considered a sign of excess visceral fat, but that may not apply if your overall body size is large.
Rather than focus on a single reading or absolute cut-off, keep an eye on whether your waist is growing are your pants getting snug at the waist? That should give you a good idea of whether you're gaining unhealthy visceral fat. Visceral fat can be measured in a variety of ways.
CT scans and full-body MRIs are the most precise, but they are expensive and rarely available, so investigators often use estimates based on waist circumference or waist size in proportion to height see "Gut check". To ensure that they're not just measuring overall obesity, researchers also check whether a person's waist circumference is higher than average for her or his body mass index BMI.
Cardiovascular disease. Several studies have documented this effect. For example, a large study of European women ages 45 to 79 concluded that those with the biggest waists and those with the largest waists in relation to their hip size had more than double the risk of developing heart disease.
The risk was still nearly double even after adjustment for several other risk factors, including blood pressure, cholesterol, smoking, and BMI. Higher visceral-fat volume also has a deleterious impact on several other heart disease risk factors.
It's associated with higher blood pressure, blood sugar levels and triglyceride levels, and lower levels of HDL good cholesterol. Taken together, these changes, known as metabolic syndrome, create a serious risk for cardiovascular disease and type 2 diabetes. Researchers at Kaiser Permanente found that people in their early 40s with the highest levels of abdominal fat, compared with those who had the least abdominal fat at that age, were nearly three times more likely to develop dementia including Alzheimer's disease by their mids to early 80s.
Dementia was not associated with increased thigh size. The risks were highest for women who were both large-waisted and overweight or obese. The investigators believe that belly fat raises the risk of asthma more than other poundage because it has inflammatory effects throughout the body, including in the airways.
Breast cancer. A combined analysis of several studies found that premenopausal women with abdominal obesity the largest waist size in proportion to their height were at greater risk for breast cancer.
Large waists were also linked to breast cancer risk among postmenopausal women, but that effect was not significant once BMI was taken into account. Colorectal cancer. People with the most visceral fat have three times the risk of developing colorectal adenomas precancerous polyps than those with the least visceral fat.
The relationship was found after many other risks were accounted for. The researchers also confirmed that adenomatous polyps in the colon are associated with insulin resistance, which may be the mechanism that increases the cancer risk. Where you tend to gain fat depends on your genes, your hormones, your age, your birth weight smaller babies more readily add belly fat later in lifeand whether you've had children women who have given birth tend to develop more visceral fat than women who haven't.
As young adults, women on average have less visceral fat than men, but that changes with menopause. You can't change your birth weight or your genes, and you can't hold off menopause. But there are several ways you can minimize the accumulation of visceral fat. The good news is that because it's more readily metabolized into fatty acids, it responds more efficiently to diet and exercise than fat on the hips and thighs.
Here are some approaches that may help:. Keep moving. Exercise can help reduce your waist circumference. Even if you don't lose weight, you lose visceral belly fat and gain muscle mass.
Engage in at least 30 minutes of moderate-intensity activity most days, such as brisk walking or bicycling at a casual pace. Also create opportunities to add motion to routine tasks.
For example, park farther from your destination and walk the rest of the way, take the stairs instead of the elevator, and stand while you talk on the phone.
Studies have shown that you can help trim visceral fat or prevent its growth with both aerobic activity such as brisk walking and strength training exercising with weights.
Spot exercises, such as sit-ups, can tighten abdominal muscles but won't get at visceral fat. Exercise can also help keep fat from coming back. Eat right. Choose a balanced diet that helps you achieve and maintain a healthy weight. Avoid products that seem to encourage belly fat deposition, especially simple sugars like fructose-sweetened foods and beverages.
Don't smoke. The more you smoke, the more likely you are to store fat in your abdomen rather than on your hips and thighs. Get your sleep. Too little is bad. A five-year study found that adults under age 40 who slept five hours or less a night accumulated significantly more visceral fat.
But too much isn't good, either — young adults who slept more than eight hours also added visceral fat. This relationship wasn't found in people over age Mind your mood.
Middle-aged women who show more hostility and had more depressive symptoms tend to have more visceral fat — but not more subcutaneous fat. Forget the quick fix. Liposuction for cosmetic fat removal doesn't reach inside the abdominal wall.
As a service to our readers, Harvard Health Publishing provides access to our library of archived content. Please note the date of last review or update on all articles. No content on this site, regardless of date, should ever be used as a substitute for direct medical advice from your doctor or other qualified clinician.
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: Visceral fat and obesity| HYPOTHESIS AND THEORY article | Extra pounds tend to Gestational diabetes monitoring themselves around the midsection. Viscegal have a obfsity Visceral fat and obesity to accumulate Viwceral visceral fat compared to pre-menopausal women. But strengthening your stomach muscles alone will not specifically reduce belly fat. Huang, J. Palmer AK, Xu M, Zhu Y, Pirtskhalava T, Weivoda MM, Hachfeld CM, et al. |
| Obese visceral fat tissue inflammation: from protective to detrimental? | BMC Medicine | Full Text | Set by the GDPR Cookie Consent plugin, this cookie is used to record the user consent for the cookies in the "Necessary" category. If you struggle to get enough sleep, try relaxing before bed or taking a magnesium supplement. Int J Obes Lond. However, animal studies indicate that matrix remodeling during chronic inflammation eventually may lead to fibrosis, i. New research suggests that running may not aid much with weight loss, but it can help you keep from gaining weight as you age. |
| Frontiers | Why Do Men Accumulate Abdominal Visceral Fat? | In mice, high-fat diet feeding studies observed an early period of 4—8 weeks with adipocyte enlargement, limited local immune activation, vasculogenesis, matrix remodeling, and clearance of a low number of dead adipocytes by local macrophages [ 81 ]. A general characteristic of tissue damage is the loss of structural integrity, i. Many of these molecules are immunostimulatory damage-associated molecular patterns DAMPs , they include stress proteins, high mobility group box 1 protein HMGB1 , DNA, some lipids, and mitochondrial structures, among many others. DAMP receptors also called pattern recognition receptors are present on innate immune cells and in part also on adaptive immune cells and non-immune cells such as epithelial cells, endothelial cells, or fibroblasts. DAMP receptors include toll-like receptors, C-type lectin receptors, cytoplasmic NLR receptors, and several DNA sensors. Signaling via these receptors leads to the production of pro-inflammatory cytokines and other mediators [ 82 , 83 ]. Dead adipocytes accumulate in obese visceral tissue and attract resident macrophages giving the image of crown-like structures resulting in phagocytic activity and proliferation. Apoptotic adipocytes express surface proteins favoring phagocytosis by M2-type macrophages [ 84 ]. Treg cells also associate with crown-like structures and probably support non-inflammatory macrophage functions [ 14 ]. However, probably because of the size difference of macrophages and hypertrophic dying adipocytes, there is also lysosomal exocytosis, and the released DAMPs stimulate pro-inflammatory immune activities which are more M1- than M2-like [ 85 ]. Immune activation by DAMPs appears to exceed pro-inflammatory signaling caused by metabolically stressed adipocytes because there is an influx of monocytes and other immune cells which outnumber resident immunocytes [ 55 , 84 ]. In mouse fat tissue, induction of inflammasome and caspase-1 activity for the release of IL-1 and IL is required for the recruitment of circulating immune cells and their pro-inflammatory activation [ 86 ]. Secretion of macrophage chemotactic protein 1 MCP-1 also contributes to monocyte attraction [ 87 , 88 ]. These cells exhibit impaired cell functions and an irreversible proliferative arrest in association with the secretion of a variety of pro-inflammatory cytokines, chemokines, proteases, and vesicles containing microRNAs, DNA, lipids, and protein. Peptides secreted in the context of the senescence-associated secretory phenotype SASP not only stimulate adipocytes and activate resident immune cells but also help recruit circulating immune cells to fat tissue followed by their activation [ 58 , 89 , 90 , 91 ]. Structural damage also ensues if physiological remodeling of the extracellular matrix of obese visceral fat tissue is insufficient to adapt to tissue growth and enhanced angiogenesis. Collagen accumulates around adipocytes and in fiber bundles leading to decreased tissue plasticity. This leads to an adipocyte-mediated release of endotrophin, a cleavage product of collagen VI, which enhances local inflammatory responses [ 92 , 93 , 94 ]. The findings described above suggest that the recruitment of immune cells and their accumulation occurs in response to structural damage of visceral fat tissue Fig. The dominant immune cells in the infiltrate are monocytes developing into tissue macrophages. Concomitantly, there is an influx of other immune cell types, including T and B cells, ILC1s, ILC3s, NK cells, mast cells, and neutrophils [ 25 , 30 , 94 , 95 , 96 , 97 , 98 , 99 ]. Since the fat tissue is not homogeneous with regard to vascularization, hypoxia, and adipocyte death, there is regional diversity of the inflammatory state. Severe visceral fat tissue inflammation in response to structural disruption. Excessive enlargement of adipocytes in response to chronic overnutrition eventually causes structural damage with dying adipocytes and cell senescence as hallmarks. The phagocytotic capacity of macrophages is overwhelmed and released DAMPS strongly activate resident immune and endothelial cells resulting in the attraction of virtually all types of immune cells. Their pro-inflammatory activation also stimulates anti-inflammatory activities. Another structural change is the accumulation of senescent cells, mostly macrophages, pre-adipocytes, mature adipocytes, and endothelial cells. Senescent cells secrete pro-inflammatory mediators and enhance the accumulation of immune cells from circulation. DAMPs and free fatty acids do not exhibit the same strong immunostimulatory activity as seen for bacterial or viral components. In inflamed obese visceral tissue infiltrated by immune cells, there is an overall dominance of pro-inflammatory activity. This situation is best researched for macrophages, which remain the prominent immune cell type in inflamed obese visceral tissue with structural damage, largely due to the recruitment of monocytes from circulation. Most infiltrated macrophages are polarized towards a pro-inflammatory phenotype which only partially resembles classic M1-like activity characterized by the secretion of IL-1ß, IL, TNFα, chemokines, and proteases [ ]. As discussed above, pro-inflammatory cytokines such as TNFα elicit the production of anti-inflammatory cytokines such as IL or of prostaglandin E2. There is regional diversity between macrophages within and outside crown-like structures, and in other human obese visceral adipose tissue [ 85 ]. For instance, macrophages with adipogenic and angiogenic gene expression patterns are distributed more evenly in the visceral fat tissue while lipid-laden pro-inflammatory macrophages are associated with dead adipocytes [ 85 ]. Obesity induced by long-term feeding of a high-fat diet in mice also changes the major phenotype of dendritic cells in visceral fat towards a pro-inflammatory profile. There is secretion of IFNα from plasmacytoid dendritic cells [ 58 ]. In parallel, the number of regulatory T cells, supporting the maintenance function of immune cells, is decreasing. The loss of Treg lymphocytes from obese visceral tissue appears to be a direct consequence of IFNα action [ 58 ]. The lower number of regulatory T cells may be the major reason accounting for a pro-inflammatory shift in several other immunocytes. Early changes include an influx of pro-inflammatory T cells and of B lymphocytes. In high-fat diet-induced obesity of mice both cell types appear to precede peak macrophage infiltration [ , ]. IFN γ secretion by CD4- and CD8-positive T lymphocytes as well as of NK cells and ILC1s probably is a strong activator of pro-inflammatory macrophage activity. Stimulation of T-cells for IFN γ production probably is supported by the pro-inflammatory B2 subset of B lymphocytes while the percentage of anti-inflammatory B1 cells is decreased [ 55 , 97 , , , , , , ]. There is also activation of MAIT cells which promotes macrophage activation by secretion of TNFα and IL [ ]. In the context of visceral obese fat tissue inflammation, there is also an increase of activated neutrophils. These cells release extracellular traps which interact with other immune cells to promote pro-inflammatory responses and possibly contribute to remodeling of the matrix because of the protease content of traps, in addition to promoting insulin resistance [ , ]. Obese visceral fat tissue also harbors increased numbers of mast cells [ ] but it is not clear whether these cells promote or dampen inflammation [ ]. The immune cell influx in response to structural damage of fat tissue appears to exhibit tissue-protective and also detrimental properties. Fat tissue repair such as elimination of dying adipocytes, enhanced lipolysis, tissue remodeling, and angiogenesis represent beneficial functions of infiltrated and resident immune cells. However, animal studies indicate that matrix remodeling during chronic inflammation eventually may lead to fibrosis, i. An alternative view suggests that a rigid extracellular membrane prevents excessive enlargement of adipocytes and supports metabolic homeostasis [ ]. Senescent cells in inflamed tissue probably also have beneficial and as well as detrimental effects. In animal models, beneficial effects include the orchestration of tissue remodeling through the secretion of pro-inflammatory factors. Senescent cells positively impact health span, liver, and vascular tissue fibrosis, and wound healing [ , ]. However, if senescent cells are not cleared within days or weeks by innate immune cells, they accumulate and spread senescence to neighboring and distant cells, mostly via secretion of microRNA-containing vesicles with the consequence of a pro-fibrotic state and deficient tissue function in hypertrophic obesity mice [ 46 , , , ]. Obesity and hyperinsulinemia also drive the senescence of adipocytes or visceral fat macrophages in humans [ 91 , ]. In obese mice, genetic or pharmacological elimination of senescent cells promoted adipogenesis and decreased the influx of monocytes into abdominal fat [ 89 , ]. When human obese visceral tissue containing senescent cells was transplanted into immunodeficient mice, lower glucose tolerance and increased insulin resistance were observed. These detrimental effects were suppressed by clearing the human fat tissue from senescent cells by treatment with a selenolytic cocktail prior to transplantation [ 90 ]. Severe visceral obesity often is accompanied by systemic low-grade inflammation, insulin resistance, glucose intolerance, and other measures of metabolic disturbances. This does not simply appear to be a spill-over effect because there seem to be contributions of other organs such as the liver, the hypothalamus, and the gut microbiota [ , , ]. Overnutrition and excess systemic nutrients cause changes in the liver related to those described for visceral fat. There is enhanced lipid uptake by several cell types followed by disturbed metabolic homeostasis as evident from endoplasmic reticulum stress in hepatocytes. Eventually, this leads to structural tissue damage such as death of hepatocytes and fibrosis. Loss of metabolic homeostasis and tissue damage is accompanied by activation of the resident immune system. Pro-inflammatory responses are carried by Kupffer cells, stellate cells, many infiltrated immune cell types, other stromal cell types, and also by hepatocytes [ , , , , , , , ]. In animal models, immune intervention trials often have led to improved metabolic control with or without decreased adiposity indicating a pathogenic role of inflammatory immune reactivity [ , , ]. However, most studies do not allow to distinguish between effects mediated at the level of the liver, pancreas, vasculature, gut, brain, or adipose tissue. A detailed discussion of diet-induced inflammatory changes outside the visceral fat tissue and of immune intervention studies is outside the scope of this paper. Inflammation of tissues in the absence of infectious, toxic or allergenic agents in general is caused by the local expression of immunostimulatory molecules in the context of metabolic or physical tissue damage. The activation of resident immune cells as well as the influx of immune cells from circulation into stressed tissue can be interpreted as an attempt to regain the previous physiological balance [ 2 , 74 ]. Loss of structure tissue damage elicits a more intense form of inflammation with influx of circulating immune cells, again primarily supporting tissue functions [ 2 ]. In obese visceral fat tissue, adaptive or repair functions of macrophages and other activated immune cells include support of matrix remodeling and angiogenesis by secretion of proteases and growth factors to accommodate for adipocyte enlargement and hyperplasia, lipid uptake and catabolism to lower lipid load, stimulation of thermogenesis for lipid burning, promotion of lipolysis and local insulin resistance to reduce lipid storage, and clearance from dead adipocytes and senescent cells. Concomitant fibrosis may be regarded as protective or detrimental, and a low density of senescent cells may favor matrix remodeling. The increase of crown-like structures and the accumulation of senescent cells suggest that repair functions become overwhelmed. Whether pro-inflammatory activities carried by the immune cell infiltrate from circulation eventually contribute to tissue damage remains to be analyzed. Finally, subtypes of visceral obesity remain to be defined, and not all of them may be represented by animal models. Subtypes may differ with respect to metabolic characteristics, age, sex or genetic background. The protective versus detrimental functions of inflammation may differ between subtypes. Only articles published in English were selected. Chen L, Deng H, Cui H, Fang J, Zuo Z, Deng J, et al. Inflammatory responses and inflammation-associated diseases in organs. Article Google Scholar. Medzhitov R. The spectrum of inflammatory responses. Article CAS Google Scholar. 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FNDC4 acts as an anti-inflammatory factor on macrophages and improves colitis in mice. Nat Commun. Meizlish ML, Franklin RA, Zhou X, Medzhitov R. Tissue Homeostasis and Inflammation. Fuchs A, Samovski D, Smith GI, Cifarelli V, Farabi SS, Yoshino J, et al. Associations Among Adipose Tissue Immunology, Inflammation, Exosomes and Insulin Sensitivity in People With Obesity and Nonalcoholic Fatty Liver Disease. Hong S, Song W, Zushin PH, Liu B, Jedrychowski MP, Mina AI, et al. Phosphorylation of Beta-3 adrenergic receptor at serine by ERK MAP kinase drives lipolysis in obese adipocytes. Foley KP, Chen Y, Barra NG, Heal M, Kwok K, Tamrakar AK, et al. Inflammation promotes adipocyte lipolysis via IRE1 kinase. J Biol Chem. Xu L, Liu W, Bai F, Xu Y, Liang X, Ma C, et al. Hepatic Macrophage as a Key Player in Fatty Liver Disease. Huang Z, Xu A. Adipose Extracellular Vesicles in Intercellular and Inter-Organ Crosstalk in Metabolic Health and Diseases. Cai Z, Huang Y, He B. New Insights into Adipose Tissue Macrophages in Obesity and Insulin Resistance. Strissel KJ, Stancheva Z, Miyoshi H, Perfield JW, DeFuria J, Jick Z, et al. Adipocyte death, adipose tissue remodeling, and obesity complications. Gong T, Liu L, Jiang W, Zhou R. DAMP-sensing receptors in sterile inflammation and inflammatory diseases. Guzman-Ruiz R, Tercero-Alcazar C, Lopez-Alcala J, Sanchez-Ceinos J, Malagon MM, Gordon A. The potential role of the adipokine HMGB1 in obesity and insulin resistance. Novel effects on adipose tissue biology. Mol Cell Endocrinol. Haase J, Weyer U, Immig K, Kloting N, Bluher M, Eilers J, et al. Local proliferation of macrophages in adipose tissue during obesity-induced inflammation. Hill DA, Lim HW, Kim YH, Ho WY, Foong YH, Nelson VL, et al. Distinct macrophage populations direct inflammatory versus physiological changes in adipose tissue. Proc Natl Acad Sci U S A. Vandanmagsar B, Youm YH, Ravussin A, Galgani JE, Stadler K, Mynatt RL, et al. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Kanda H, Tateya S, Tamori Y, Kotani K, Hiasa K, Kitazawa R, et al. MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. Dommel S, Bluher M. Does C-C Motif Chemokine Ligand 2 CCL2 Link Obesity to a Pro-Inflammatory State? Palmer AK, Xu M, Zhu Y, Pirtskhalava T, Weivoda MM, Hachfeld CM, et al. Targeting senescent cells alleviates obesity-induced metabolic dysfunction. Aging Cell. Wang L, Wang B, Gasek NS, Zhou Y, Cohn RL, Martin DE, et al. Targeting p21 Cip1 highly expressing cells in adipose tissue alleviates insulin resistance in obesity. Matacchione G, Perugini J, Di ME, Sabbatinelli J, Prattichizzo F, Senzacqua M, et al. Senescent macrophages in the human adipose tissue as a source of inflammaging. Sun K, Park J, Gupta OT, Holland WL, Auerbach P, Zhang N, et al. Endotrophin triggers adipose tissue fibrosis and metabolic dysfunction. Marcelin G, Silveira ALM, Martins LB, Ferreira AV, Clement K. Deciphering the cellular interplays underlying obesity-induced adipose tissue fibrosis. Qi Y, Hui X. The shades of grey in adipose tissue reprogramming. Biosci Rep. Winer DA, Winer S, Shen L, Wadia PP, Yantha J, Paltser G, et al. B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies. Brestoff JR, Artis D. Immune regulation of metabolic homeostasis in health and disease. Wensveen FM, Jelencic V, Valentic S, Sestan M, Wensveen TT, Theurich S, et al. NK cells link obesity-induced adipose stress to inflammation and insulin resistance. McLaughlin T, Ackerman SE, Shen L, Engleman E. Role of innate and adaptive immunity in obesity-associated metabolic disease. Hildreth AD, Ma F, Wong YY, Sun R, Pellegrini M, O'Sullivan TE. Single-cell sequencing of human white adipose tissue identifies new cell states in health and obesity. Kratz M, Coats BR, Hisert KB, Hagman D, Mutskov V, Peris E, et al. Metabolic dysfunction drives a mechanistically distinct proinflammatory phenotype in adipose tissue macrophages. Snodgrass RG, Boss M, Zezina E, Weigert A, Dehne N, Fleming I, et al. Hypoxia Potentiates Palmitate-induced Pro-inflammatory Activation of Primary Human Macrophages. Boutens L, Hooiveld GJ, Dhingra S, Cramer RA, Netea MG, Stienstra R. Unique metabolic activation of adipose tissue macrophages in obesity promotes inflammatory responses. Lee YS, Olefsky J. Chronic tissue inflammation and metabolic disease. Lee BC, Kim MS, Pae M, Yamamoto Y, Eberle D, Shimada T, et al. Adipose Natural Killer Cells Regulate Adipose Tissue Macrophages to Promote Insulin Resistance in Obesity. Li C, Menoret A, Farragher C, Ouyang Z, Bonin C, Holvoet P, et al. Single cell transcriptomics based-MacSpectrum reveals novel macrophage activation signatures in diseases. Caslin HL, Bhanot M, Bolus WR, Hasty AH. Adipose tissue macrophages: Unique polarization and bioenergetics in obesity. Immunol Rev. Kintscher U, Hartge M, Hess K, Foryst-Ludwig A, Clemenz M, Wabitsch M, et al. T-lymphocyte infiltration in visceral adipose tissue: a primary event in adipose tissue inflammation and the development of obesity-mediated insulin resistance. Duffaut C, Galitzky J, Lafontan M, Bouloumie A. Unexpected trafficking of immune cells within the adipose tissue during the onset of obesity. Biochem Biophys Res Commun. Nishimura S, Manabe I, Nagasaki M, Eto K, Yamashita H, Ohsugi M, et al. O'Rourke RW, White AE, Metcalf MD, Winters BR, Diggs BS, Zhu X, et al. Systemic inflammation and insulin sensitivity in obese IFN-gamma knockout mice. Ferno J, Strand K, Mellgren G, Stiglund N, Bjorkstrom NK. Natural Killer Cells as Sensors of Adipose Tissue Stress. Toubal A, Kiaf B, Beaudoin L, Cagninacci L, Rhimi M, Fruchet B, et al. Mucosal-associated invariant T cells promote inflammation and intestinal dysbiosis leading to metabolic dysfunction during obesity. Talukdar S, Oh DY, Bandyopadhyay G, Li D, Xu J, McNelis J, et al. Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase. Freitas DF, Colon DF, Silva RL, Santos EM, Guimaraes VHD, Ribeiro GHM, et al. Neutrophil extracellular traps NETs modulate inflammatory profile in obese humans and mice: adipose tissue role on NETs levels. Mol Biol Rep. Divoux A, Moutel S, Poitou C, Lacasa D, Veyrie N, Aissat A, et al. Mast cells in human adipose tissue: link with morbid obesity, inflammatory status, and diabetes. J Clin Endocrinol Metab. Goldstein N, Kezerle Y, Gepner Y, Haim Y, Pecht T, Gazit R, et al. Higher Mast Cell Accumulation in Human Adipose Tissues Defines Clinically Favorable Obesity Sub-Phenotypes. Khan T, Muise ES, Iyengar P, Wang ZV, Chandalia M, Abate N, et al. Metabolic dysregulation and adipose tissue fibrosis: role of collagen VI. Mol Cell Biol. Datta R, Podolsky MJ, Atabai K. Fat fibrosis: friend or foe? JCI Insight. Grosse L, Wagner N, Emelyanov A, Molina C, Lacas-Gervais S, Wagner KD, et al. Defined p16 High Senescent Cell Types Are Indispensable for Mouse Healthspan. Demaria M, Ohtani N, Youssef SA, Rodier F, Toussaint W, Mitchell JR, et al. An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA. Dev Cell. The fat inside your belly the visceral fat can be seen and measured, but not pinched. How do you lose belly fat? No surprise: exercise and diet. Staying physically active throughout the day as well as scheduling time for structured exercise may be even more important than diet. Research suggests that fat cells — particularly abdominal fat cells — are biologically active. It's appropriate to think of fat as an endocrine organ or gland, producing hormones and other substances that can profoundly affect our health. Although scientists are still deciphering the roles of individual hormones, it's becoming clear that excess body fat, especially abdominal fat, disrupts the normal balance and functioning of these hormones. Scientists are also learning that visceral fat pumps out immune system chemicals called cytokines — for example, tumor necrosis factor and interleukin-6 — that can increase the risk of cardiovascular disease. These and other biochemicals are thought to have deleterious effects on cells' sensitivity to insulin, blood pressure, and blood clotting. One reason excess visceral fat is so harmful could be its location near the portal vein, which carries blood from the intestinal area to the liver. Substances released by visceral fat, including free fatty acids, enter the portal vein and travel to the liver, where they can influence the production of blood lipids. Visceral fat is directly linked with higher total cholesterol and LDL bad cholesterol, lower HDL good cholesterol, and insulin resistance. Insulin resistance means that your body's muscle and liver cells don't respond adequately to normal levels of insulin, the pancreatic hormone that carries glucose into the body's cells. Glucose levels in the blood rise, heightening the risk for diabetes. Now for the good news. So what can we do about tubby tummies? A lot, it turns out. The starting point for bringing weight under control, in general, and combating abdominal fat, in particular, is regular moderate-intensity physical activity — at least 30 minutes per day and perhaps up to 60 minutes per day to control weight and lose belly fat. Strength training exercising with weights may also help fight abdominal fat. Spot exercising, such as doing sit-ups, can tighten abdominal muscles, but it won't get at visceral fat. Diet is also important. Pay attention to portion size, and emphasize complex carbohydrates fruits, vegetables, and whole grains and lean protein over simple carbohydrates such as white bread, refined-grain pasta, and sugary drinks. Replacing saturated fats and trans fats with polyunsaturated fats can also help. Scientists hope to develop drug treatments that target abdominal fat. For now, experts stress that lifestyle, especially exercise, is the very best way to fight visceral fat. As a service to our readers, Harvard Health Publishing provides access to our library of archived content. Please note the date of last review or update on all articles. No content on this site, regardless of date, should ever be used as a substitute for direct medical advice from your doctor or other qualified clinician. Thanks for visiting. Don't miss your FREE gift. 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| How to Get Rid of Visceral Fat | In essence, β receptors are lipolytic and α2A receptors are anti-lipolytic. The sex differences in body composition have been well established Karastergiou et al. How we reviewed this article: Sources. Heart Assoc. According to official guidelines, the bottom of the tape measure should be level with the top of the right hip bone, or ilium — see the illustration — at the point where the ilium intersects a line dropped vertically from the center of the armpit. |
| How to Get Rid of Visceral Fat | Visceral fat and obesity Best Fatt for Cognitive Fitnessis yours absolutely FREE when you Emotional well-being support up to receive Health Alerts Visceral fat and obesity Harvard Ane School Sign up to get tips onesity living a healthy obesitu, with ways to Sustainable meal delivery services inflammation and improve cognitive healthVisceral fat and obesity the latest advances in preventative medicine, diet and exercisepain relief, blood pressure and cholesterol management, and more. Due to their smaller size, some of the VLDLs can readily enter the lumen of the blood capillaries. Stay on top of latest health news from Harvard Medical School. No matter what your body shape, excess fat isn't good for your health. ICD - 10 : E66 ICD - 9-CM : MeSH : D Medical News Today has strict sourcing guidelines and draws only from peer-reviewed studies, academic research institutions, and medical journals and associations. |
Visceral fat and obesity -
In visceral fat, members of the innate as well as adaptive immune system have been identified. These include macrophages, dendritic cells, granulocytes, innate lymphoid cells ILCs and natural killer NK cells , and also T and B cells [ 3 ] Fig.
Single-cell transcriptome analysis of mouse lean visceral adipose tissue leukocytes identified 15 distinct subpopulations [ 4 ]. In normal non-inflamed tissue, these cells are not only immune guardians against infection but also support proper tissue function.
Many of these findings originate from studies in experimental models, but where analyzed, similar physiological functions of immune cells have also been reported in humans [ 5 ]. For instance, macrophages exhibit functional heterogeneity which includes the removal of dead or apoptotic fat cells, remodeling the extracellular matrix and promoting angiogenesis [ 5 ].
A subtype of macrophages supports the control of lipid metabolism by uptake and digestion of lipids [ 6 , 7 ]. Furthermore, the secretion of IL appears to be a major pathway of promoting thermogenesis in fat cells [ 8 ]. Macrophages contribute to the regulation of thermogenesis in response to cold exposure [ 9 ].
There is no homogeneous distribution of macrophage subtypes. For instance, in human subcutaneous tissue, spatial mapping identified macrophages with a M1-like phenotype associated with niches of adipocyte progenitor cells while macrophages with a non-inflammatory phenotype were dispersed throughout the fat tissue [ 10 ].
Network and physiological functions of resident immune cells in lean visceral adipose tissue. In the absence of metabolic or inflammatory stress resident immune cells interact among themselves and with adipocytes and stromal cells to maintain proper tissue functions.
There are no signature cytokines defining the maintenance state of resident immune cells. Cytokines, chemokines, acute phase proteins, and other immune mediators are released in small amounts mostly from resident immune cells but also from mesenchymal stromal cells and adipocytes. Several macrophage subtypes promote matrix remodeling and angiogenesis, phagocytose dead cell and lipid aggregates, and promote adipocyte thermogenesis.
ILC2 also supports adipocyte thermogenesis and stimulates physiological eosinophil functions. Regulatory T cells promote tissue repair and interact with macrophages and other immune cell types to maintain a non-inflammatory state. Low-level secretion of immune mediators by macrophages, dendritic cells, and other immune cell types such as ILC2s, iNKTs, Th2 cells, γδT cells, B-1b cells, and eosinophils helps to prevent immune cell activation.
For better readability, only a few key intercellular signals are included in the scheme. ATM, adipose tissue macrophage; DC, dendritic cell; IL, interleukin; ILC, innate lymphoid cell; iNKT, innate natural killer T cell; MetEnk, methionine-enkephalin peptides; NK, natural killer cell.
ILC2 cells contribute to the regulation of energy expenditure by promoting the differentiation of beige adipocytes from adipocyte precursors or beiging of white fat cells in visceral tissues via upregulation of uncoupling protein 1 UCP1 by enkephalin peptides [ 11 , 12 ].
ILC2-derived IL helps to prevent pro-inflammatory activation of macrophages, dendritic cells, ILC1, and natural killer cells. By secreting IL-5, ILC2 cells promote anti-inflammatory eosinophil activity. Conventional dendritic cells exhibit a tolerogenic phenotype, characterized by IL production and suppression of Th1-promoting activity by upregulated expression of peroxisome proliferator-activated receptor gamma PPAR-γ [ 13 ].
Regulatory T cells Treg represent the major CD4-positive T cell type, they participate in tissue repair and preserve Glut-4 expression by adipocytes [ 14 , 15 ]. Interestingly, the majority of Tregs appear to be oligoclonal in mice as indicated by distinct T cell receptor repertoires.
There may be MHC II-dependent antigen recognition involved, as suggested by the close association with resident macrophages and dendritic cells [ 16 ]. The primary function of Tregs probably is to keep other immune cell types in a neutral physiological state, i.
Resident B-1b lymphocytes secrete natural IgM antibodies and promote adipose physiological functions by suppressing B-2 cells, in mice and humans [ 17 ]. In addition, B-1 cells comprise the major cell type of fat-associated lymphoid clusters which appear to contribute to humoral immune responses to peritoneal antigens [ 18 ].
Lymphoid clusters in mice and humans are also a rich source of Th2-like cytokines released from innate Th2-like lymphoid cells [ 19 , 20 ].
Fat-associated lymphoid clusters such as milky spots on the omentum surface probably serve immune functions of the peritoneal cavity rather than supporting physiological fat tissue functions.
Indeed, the numbers of milky spots increase during peritoneal inflammation in response to local TNFα and innate natural killer T cell activity [ 20 , 21 ]. Studies in mice suggest that sympathetic innervation is promoted by γδT cells by signaling via the IL receptor C to induce TGFß1 production by parenchymal cells [ 22 ].
Further, sympathetic neuron-associated macrophages SAMs regulate neuron growth and modulate adrenergic signaling [ 23 ]. Based mostly on animal studies, the continuous release of anti-inflammatory mediators from macrophages, dendritic cells, Th2-cells, γδT cells, eosinophils, mucosa-associated invariant T cells MAIT , and invariant natural killer T cells appears to further help maintain metabolic homeostasis [ 14 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ] Fig.
The support of tissue functions by resident immune cells involves interactions with non-immune tissue cells including adipocytes, endothelial cells, neurons, fibroblasts, and other mesenchymal stromal cells [ 3 , 33 , 34 ].
In the absence of immunologic stimuli, immune mediator secretion from resident immune cells and other fat tissue cells is low.
The local immune milieu is well buffered, i. Further, pro-inflammatory TNFα and ILA induce counterregulatory IL for the stimulation of anti-inflammatory Tregs and ILC2s [ 15 , 35 , 36 ]. Taken together, in lean visceral adipose tissue, there is a physiological network of adipocytes, stromal cells, and immune cells.
The resident immune system is not dormant but supports overall tissue functions. Cytokines, chemokines, acute phase proteins, and other immune mediators are released in small amounts mostly from resident immune cells but also from mesenchymal stromal cells and adipocytes [ 37 , 38 ].
The primary cause of progression from lean to obese visceral fat tissue is excess calorie intake, including digestible carbohydrates. Human metabolic control usually is geared in such a way that a calorie surplus is not disposed of by generating additional thermal energy but is stored to a large degree as triglycerides in adipocytes.
Excess calorie consumption causes an increase of circulating insulin levels after and between meals. Being an anabolic hormone, insulin suppresses lipolysis and promotes fat storage in adipocytes already at concentrations that are in the high normal range or which are slightly elevated.
Pharmacological or experimental lowering of insulin levels indeed ameliorates obesity which indicates that the support of lipogenesis by insulin is obesogenic reviewed by [ 39 ]. These regulatory effects of insulin do not apply for all adipocytes.
In subcutaneous tissue about half of mature adipocytes are insulin responsive, the two other subtypes exhibit little or no increased transcriptional activity when exposed to hyperinsulinemia [ 10 ]. Anabolic activity of visceral fat tissue in response to overnutrition involves adipocyte enlargement and hyperplasia to accommodate for increased requirements of energy storage, i.
Lipogenesis leads to enlargement of mature adipocytes because of more fat stored in one large lipid droplet organelle. There is also differentiation and growth of preadipocytes, but in visceral fat hyperplasia contributes less to the increase of fat mass than adipocyte hypertrophy [ 41 ].
The formation of new fat-laden adipocytes from precursor cells appears to begin when enlarged mature adipocytes reach a critical cell size and release mediators stimulating preadipocyte growth and differentiation [ 42 , 43 ]. Fat cell hyperplasia thus is a second pathway of coping with excess circulating nutrients Fig.
Response of visceral fat tissue to excess calories by adipocyte hypertrophy and hyperplasia. In response to high levels of circulating glucose, triglycerides, and the anabolic hormone insulin mature adipocytes take up increased amounts of nutrients and store excess energy as triglycerides in one large lipid droplet organelle.
The cell size may increase 10—fold in diameter. Enlarged adipocytes secrete factors favoring angiogenesis and remodeling of the extracellular matrix and release of growth factors which is essential for mesenchymal stem cells, adipocyte progenitors, and preadipocytes to differentiate into lipid-storing mature adipocytes.
In parallel, macrophages are stimulated to support angiogenesis and matrix remodeling. ATM, adipocyte tissue macrophages; TGs, triglycerides; Glc, glucose; ECM, extracellular matrix; Pro-inflamm.
Studies in mice indicate that a major obstacle to fat tissue expansion in response to high-fat diet feeding is the collagen network of the extracellular matrix.
A major source of collagen is perivascular cells in response to signaling via the platelet-derived growth factor 1α [ 44 ]. Most relevant for limiting fat tissue expansion is the extracellular matrix of niches rich in adipocyte precursors.
Interestingly, these niches harbor potentially pro-inflammatory macrophages [ 10 ] and induction of acute local inflammation, for instance by injection of low-dose lipopolysaccharide enhances fibrolysis and remodeling of the extracellular matrix, and promotes angiogenesis to allow for efficient adipocyte hyperplasia.
Enlarged adipocytes initiate fat tissue remodeling by secreting angiogenic factors such as such as fibroblast growth factor-2, vascular endothelial growth factor, human growth factor, and other mediators such as extracellular matrix proteases Fig. Efficient remodeling requires activation of pro-inflammatory macrophages by hypertrophic adipocytes which appears to be a physiological response needed for fat tissue growth because downregulation of pro-inflammatory reactivity prevents proper adipocyte hyperplasia [ 41 , 45 , 46 ].
Thus, at least initially, inflammation in adipose tissue is a physiological adaptive response which improves fat tissue plasticity and consequently preserves metabolic control and insulin sensitivity [ 47 ].
A similar important role of inflammatory reactions, such as activation of the NLRP3 inflammasome, has been reported to drive postburn white adipose tissue remodeling [ 48 ]. Storage of energy in form of triglycerides also occurs in other fat tissues of the body, notably subcutaneous fat.
The adipogenic activity and the ability to mobilize preadipocytes in response to overeating have been reported to be delayed in subcutaneous fat and therefore may be insufficient to lower the metabolic stress of visceral fat tissue during excess calorie intake [ 43 ].
However, this is different in persons with true metabolic healthy obesity, i. In these persons, the growth of visceral fat and adipocyte enlargement is only moderate, and excess nutrients are primarily handled by enlargement and hyperplasia of adipocytes in subcutaneous fat tissue, primarily in the superficial layer [ 43 , 50 , 51 , 52 ].
In sum, the primary fat tissue response to excess calorie intake includes enlargement of adipocytes, differentiation of new mature cells from pre-adipocytes or stem cells, all supported by remodeling of the extracellular matrix, and of angiogenesis for appropriate blood supply.
Growth of visceral fat tissue is not possible without appropriate remodeling of the vasculature and the extracellular matrix surrounding preadipocytes and small adipocytes.
Enlarged adipocytes initiate these changes by secreting factors promoting angiogenesis and matrix remodeling. These adaptive responses are characteristic of metabolically healthy obesity. A recent overview of inflammatory responses to non-infectious stimuli in various tissues of the body has concluded that there appear to be three types of perturbation causing an inflammatory response which, at least initially, are considered protective [ 2 ] The suggested hierarchy of perturbations is loss of regulation, loss of function and loss of structure.
This concept is applied here to obese fat tissue, and the current section considers loss of regulation. In those visceral adipose regions where the adaptive response to excess energy influx has reached a limit, metabolic homeostasis is lost, and activation of resident immune cells occurs.
In detail, strongly enlarged adipocytes fail to maintain metabolic homeostasis of lipid storage versus lipolysis because the lipid overload leads to endoplasmic reticulum stress, increased expression of the inflammation regulator NF-kB and the production of inflammation-inducing signals such as IL-6 [ 40 , 53 ].
The secretion of pro-inflammatory mediators in response to loss of metabolic homeostasis has been termed metaflammation [ 54 ]. Enlarged adipocytes exhibit additional responses to caloric stress.
For instance, adipocytes respond to high ambient nutrient concentrations with the release of leptin and other hormones which target the brain to limit food intake and increase the sympathetic tone.
Adrenaline and noradrenaline are released from nerve endings in adipose tissue and activate lipolysis by signaling via ß-adrenergic receptors of adipocytes.
Sympathetic neuron-associated macrophages may function as rate-limiters by degrading noradrenaline via monoamine oxidase A [ 23 ]. The locally increased concentration of non-esterified fatty acids is expected to activate pro-inflammatory macrophage functions.
This may involve co-secretion of adipocyte fatty acid binding protein FABP4 , induction of FABP4 in macrophages, and signaling via toll-like receptors TLR4 and TLR2. Free fatty acids do not directly bind to TLR4, but lipid metabolism within macrophages is affected by the influx of free fatty acids which has pro-inflammatory consequences if there is simultaneous activation of TLR4.
The latter may result from increased levels of lipopolysaccharide released from gut microbiota in the context of gut leakiness during an obesogenic diet [ 55 , 56 , 57 , 58 , 59 , 60 ]. Further, recent studies suggest a role of adenine nucleotide translocase 2 in mediating free fatty acid-induced mitochondrial dysfunction, increased oxygen radical production and NF-kB activation in fat tissue macrophages [ 61 ].
The secretion of leptin by enlarged adipocytes not only limits food intake and promotes lipolysis in visceral fat but also engages leptin receptors present on most immune cells. Another pathway of promoting local inflammation in response to adipocyte enlargement is activated by rapid fat tissue growth in the presence of insufficient angiogenesis which lowers capillary density and increases diffusion distance for oxygen eventually resulting in a hypoxic environment of enlarged adipocytes.
Adipose is among the most vascularized tissues with each adipocyte surrounded by capillaries [ 63 ]. Lowering ambient oxygen concentration in adipocyte culture caused a switch from oxidative phosphorylation to anaerobic glycolysis and changed the expression of more than genes [ 64 ].
One major mediator of this response is hypoxia-inducible factor 1α [ 55 ]. Pro-inflammatory mediators secreted by mature adipocytes during hypoxia include chemokines and cytokines such as PAI-1, CCL5, and IL-6 as well as micro RNAs [ 65 , 66 , 67 , 68 ] Fig.
A subset of macrophages is closely associated with the vasculature and characterized by the expression of lymphatic vessel endothelial hyaluronan receptor 1.
These macrophages support angiogenesis by producing tissue remodeling growth factors and metalloproteinases [ 21 , 69 ]. Hypoxia does not homogeneously affect visceral fat tissue but is a regional phenomenon as concluded from immunohistochemical staining for hypoxia-inducible factor 1α.
The colocalization of enhanced numbers of macrophages and T cells supports the pro-inflammatory property of hypoxia [ 70 ]. Local inflammation in response to disturbed adipocyte metabolic homeostasis.
When enhanced lipid storage via adipocyte enlargement and differentiation of progenitor cells fails to maintain metabolic homeostasis, local inflammatory changes occur in order to dispose of excess lipid and regain metabolic control.
For one, lipid-laden adipocytes experience endoplasmic reticulum stress and increased expression of NFkB leading to the release of pro-inflammatory mediators such as IL Additional pro-inflammatory signals are delivered by the release of free fatty acids, leptin, lipopolysaccharides, and other products of an unbalanced microbiota in the context of a leaky gut.
Activated resident immune cells release amounts of pro-inflammatory mediators sufficient to promote lipolysis and suppress lipid storage in part via induction of insulin resistance.
In addition, there is an uptake of lipids by macrophages and storage in small lipid droplets. Leptin interacts with receptors in the brain to limit food intake and increase the sympathetic tone.
The increased local release of noradrenaline also promotes lipolysis. Another pro-inflammatory condition results from hypoxia due to local enlargement of adipocytes.
The concomitant release of enzymes and factors promoting tissue remodeling and angiogenesis may be considered a healing response. Enlarged adipocytes overexpress MHC class II antigens and appear to present antigens to CD4-positive T cells.
Another pathway of limiting energy storage is the induction of adipocyte beiging by transdifferentiation or growth from progenitors and the disposal of excess energy by thermogenesis. A third pathway of pro-inflammatory activation of resident immune cells is suggested by the finding that hypertrophic adipocytes overexpress major histocompatibility antigens class II MHCII and produce costimulatory molecules for effective antigen presentation to CD4 positive T cells.
Although antigens presented have not been identified, it is remarkable that mice with genetic depletion of MHC II in adipocytes gain weight as control mice but do not develop adipose tissue inflammation and insulin resistance [ 71 ].
An additional pathway of lowering the metabolic stress in obese visceral fat tissue is the transdifferentiation of white adipocytes to beige adipocytes and the formation of new beige adipocytes from precursor cells Fig.
Beige adipocytes contain several smaller lipid droplet organelles and more mitochondria than hypertrophic adipocytes for burning free fatty acids to generate heat. Secretion of IL from macrophages promotes thermogenesis in fat cells [ 8 ], as does the release of enkephalin peptides from ILC2 cells [ 11 , 12 ].
The major mediator of beiging in visceral fat released by adipocytes in obesity is fibronectin type III domain-containing protein 4 FNDC4 which probably targets the receptor GRP There is a positive association between the expression of FNDC4 and obesity-associated inflammation [ 72 ]. In line with a role in regaining normal tissue homeostasis, FNDC4 exhibits anti-inflammatory properties in macrophages [ 73 ].
Taken together, loss of metabolic homeostasis in fat tissue is sufficient to initiate a local pro-inflammatory response. Secretion of pro-inflammatory mediators from macrophages and other immune cells substantially exceeds the release from adipocytes [ 38 ]. This may be viewed as an attempt to restore proper energy balance [ 74 ].
The locally enhanced concentrations of mediators like TNFα, IL-1, and IL-6 act back on adipocytes and suppress further lipid storage by inhibiting lipoprotein lipase, needed for lipid uptake, and by promoting lipolysis and fatty acid release via several pathways. These include the local induction of insulin resistance in insulin-sensitive adipocytes resulting from engaging TNFα or other pro-inflammatory mediators including microRNAs and subsequent impairment of insulin signaling for lipolysis inhibition [ 26 , 75 ].
Further support comes from increased activation of extracellular signal-regulated kinase ERK stimulating beta3 adrenergic receptor-mediated lipolysis via protein kinase A [ 76 ]. Inflammatory stress induces kinase activity of inositol-requiring protein 1 IRE-1 , a component of the endoplasmic reticulum stress response, which is also followed by enhanced lipolysis [ 77 ].
In addition, there is upregulation of lysosomal biogenesis, increased uptake and turnover of lipids, and increased formation of lipid droplets in macrophages, all of which can be considered an attempt to lower the lipid load of adipocytes [ 78 ]. The interaction between the various cell types in adipose tissue can also be described as crosstalk since there is signaling between cells in both directions.
Crosstalk not only involves the secretion of soluble mediators but also of particulate structures such as extracellular vesicles or mitochondria [ 79 , 80 ]. The scenario described relates to observations in animal models. In humans, the direct demonstration an early phase of inflammatory reactions induced by metabolically stressed enlarged adipocytes during overnutrition would require repeated biopsies of visceral fat tissue, but the mechanisms detailed above also apply to human cells.
In mice, high-fat diet feeding studies observed an early period of 4—8 weeks with adipocyte enlargement, limited local immune activation, vasculogenesis, matrix remodeling, and clearance of a low number of dead adipocytes by local macrophages [ 81 ]. A general characteristic of tissue damage is the loss of structural integrity, i.
Many of these molecules are immunostimulatory damage-associated molecular patterns DAMPs , they include stress proteins, high mobility group box 1 protein HMGB1 , DNA, some lipids, and mitochondrial structures, among many others. DAMP receptors also called pattern recognition receptors are present on innate immune cells and in part also on adaptive immune cells and non-immune cells such as epithelial cells, endothelial cells, or fibroblasts.
DAMP receptors include toll-like receptors, C-type lectin receptors, cytoplasmic NLR receptors, and several DNA sensors. Signaling via these receptors leads to the production of pro-inflammatory cytokines and other mediators [ 82 , 83 ]. Dead adipocytes accumulate in obese visceral tissue and attract resident macrophages giving the image of crown-like structures resulting in phagocytic activity and proliferation.
Apoptotic adipocytes express surface proteins favoring phagocytosis by M2-type macrophages [ 84 ]. Treg cells also associate with crown-like structures and probably support non-inflammatory macrophage functions [ 14 ]. However, probably because of the size difference of macrophages and hypertrophic dying adipocytes, there is also lysosomal exocytosis, and the released DAMPs stimulate pro-inflammatory immune activities which are more M1- than M2-like [ 85 ].
Immune activation by DAMPs appears to exceed pro-inflammatory signaling caused by metabolically stressed adipocytes because there is an influx of monocytes and other immune cells which outnumber resident immunocytes [ 55 , 84 ].
In mouse fat tissue, induction of inflammasome and caspase-1 activity for the release of IL-1 and IL is required for the recruitment of circulating immune cells and their pro-inflammatory activation [ 86 ]. Secretion of macrophage chemotactic protein 1 MCP-1 also contributes to monocyte attraction [ 87 , 88 ].
These cells exhibit impaired cell functions and an irreversible proliferative arrest in association with the secretion of a variety of pro-inflammatory cytokines, chemokines, proteases, and vesicles containing microRNAs, DNA, lipids, and protein. Peptides secreted in the context of the senescence-associated secretory phenotype SASP not only stimulate adipocytes and activate resident immune cells but also help recruit circulating immune cells to fat tissue followed by their activation [ 58 , 89 , 90 , 91 ].
Structural damage also ensues if physiological remodeling of the extracellular matrix of obese visceral fat tissue is insufficient to adapt to tissue growth and enhanced angiogenesis. Collagen accumulates around adipocytes and in fiber bundles leading to decreased tissue plasticity.
This leads to an adipocyte-mediated release of endotrophin, a cleavage product of collagen VI, which enhances local inflammatory responses [ 92 , 93 , 94 ]. The findings described above suggest that the recruitment of immune cells and their accumulation occurs in response to structural damage of visceral fat tissue Fig.
The dominant immune cells in the infiltrate are monocytes developing into tissue macrophages. Concomitantly, there is an influx of other immune cell types, including T and B cells, ILC1s, ILC3s, NK cells, mast cells, and neutrophils [ 25 , 30 , 94 , 95 , 96 , 97 , 98 , 99 ]. Since the fat tissue is not homogeneous with regard to vascularization, hypoxia, and adipocyte death, there is regional diversity of the inflammatory state.
Severe visceral fat tissue inflammation in response to structural disruption. Excessive enlargement of adipocytes in response to chronic overnutrition eventually causes structural damage with dying adipocytes and cell senescence as hallmarks.
The phagocytotic capacity of macrophages is overwhelmed and released DAMPS strongly activate resident immune and endothelial cells resulting in the attraction of virtually all types of immune cells.
Their pro-inflammatory activation also stimulates anti-inflammatory activities. Another structural change is the accumulation of senescent cells, mostly macrophages, pre-adipocytes, mature adipocytes, and endothelial cells.
Senescent cells secrete pro-inflammatory mediators and enhance the accumulation of immune cells from circulation.
DAMPs and free fatty acids do not exhibit the same strong immunostimulatory activity as seen for bacterial or viral components. In inflamed obese visceral tissue infiltrated by immune cells, there is an overall dominance of pro-inflammatory activity.
This situation is best researched for macrophages, which remain the prominent immune cell type in inflamed obese visceral tissue with structural damage, largely due to the recruitment of monocytes from circulation.
Most infiltrated macrophages are polarized towards a pro-inflammatory phenotype which only partially resembles classic M1-like activity characterized by the secretion of IL-1ß, IL, TNFα, chemokines, and proteases [ ].
As discussed above, pro-inflammatory cytokines such as TNFα elicit the production of anti-inflammatory cytokines such as IL or of prostaglandin E2. There is regional diversity between macrophages within and outside crown-like structures, and in other human obese visceral adipose tissue [ 85 ].
For instance, macrophages with adipogenic and angiogenic gene expression patterns are distributed more evenly in the visceral fat tissue while lipid-laden pro-inflammatory macrophages are associated with dead adipocytes [ 85 ].
Obesity induced by long-term feeding of a high-fat diet in mice also changes the major phenotype of dendritic cells in visceral fat towards a pro-inflammatory profile. There is secretion of IFNα from plasmacytoid dendritic cells [ 58 ].
In parallel, the number of regulatory T cells, supporting the maintenance function of immune cells, is decreasing. The loss of Treg lymphocytes from obese visceral tissue appears to be a direct consequence of IFNα action [ 58 ].
The lower number of regulatory T cells may be the major reason accounting for a pro-inflammatory shift in several other immunocytes.
Early changes include an influx of pro-inflammatory T cells and of B lymphocytes. In high-fat diet-induced obesity of mice both cell types appear to precede peak macrophage infiltration [ , ]. IFN γ secretion by CD4- and CD8-positive T lymphocytes as well as of NK cells and ILC1s probably is a strong activator of pro-inflammatory macrophage activity.
Stimulation of T-cells for IFN γ production probably is supported by the pro-inflammatory B2 subset of B lymphocytes while the percentage of anti-inflammatory B1 cells is decreased [ 55 , 97 , , , , , , ]. There is also activation of MAIT cells which promotes macrophage activation by secretion of TNFα and IL [ ].
In the context of visceral obese fat tissue inflammation, there is also an increase of activated neutrophils. These cells release extracellular traps which interact with other immune cells to promote pro-inflammatory responses and possibly contribute to remodeling of the matrix because of the protease content of traps, in addition to promoting insulin resistance [ , ].
Obese visceral fat tissue also harbors increased numbers of mast cells [ ] but it is not clear whether these cells promote or dampen inflammation [ ].
The immune cell influx in response to structural damage of fat tissue appears to exhibit tissue-protective and also detrimental properties. Fat tissue repair such as elimination of dying adipocytes, enhanced lipolysis, tissue remodeling, and angiogenesis represent beneficial functions of infiltrated and resident immune cells.
However, animal studies indicate that matrix remodeling during chronic inflammation eventually may lead to fibrosis, i.
An alternative view suggests that a rigid extracellular membrane prevents excessive enlargement of adipocytes and supports metabolic homeostasis [ ].
Senescent cells in inflamed tissue probably also have beneficial and as well as detrimental effects. In animal models, beneficial effects include the orchestration of tissue remodeling through the secretion of pro-inflammatory factors.
Senescent cells positively impact health span, liver, and vascular tissue fibrosis, and wound healing [ , ]. However, if senescent cells are not cleared within days or weeks by innate immune cells, they accumulate and spread senescence to neighboring and distant cells, mostly via secretion of microRNA-containing vesicles with the consequence of a pro-fibrotic state and deficient tissue function in hypertrophic obesity mice [ 46 , , , ].
Obesity and hyperinsulinemia also drive the senescence of adipocytes or visceral fat macrophages in humans [ 91 , ]. In obese mice, genetic or pharmacological elimination of senescent cells promoted adipogenesis and decreased the influx of monocytes into abdominal fat [ 89 , ].
When human obese visceral tissue containing senescent cells was transplanted into immunodeficient mice, lower glucose tolerance and increased insulin resistance were observed. These detrimental effects were suppressed by clearing the human fat tissue from senescent cells by treatment with a selenolytic cocktail prior to transplantation [ 90 ].
Severe visceral obesity often is accompanied by systemic low-grade inflammation, insulin resistance, glucose intolerance, and other measures of metabolic disturbances. This does not simply appear to be a spill-over effect because there seem to be contributions of other organs such as the liver, the hypothalamus, and the gut microbiota [ , , ].
Overnutrition and excess systemic nutrients cause changes in the liver related to those described for visceral fat. There is enhanced lipid uptake by several cell types followed by disturbed metabolic homeostasis as evident from endoplasmic reticulum stress in hepatocytes.
Eventually, this leads to structural tissue damage such as death of hepatocytes and fibrosis. Loss of metabolic homeostasis and tissue damage is accompanied by activation of the resident immune system. Pro-inflammatory responses are carried by Kupffer cells, stellate cells, many infiltrated immune cell types, other stromal cell types, and also by hepatocytes [ , , , , , , , ].
In animal models, immune intervention trials often have led to improved metabolic control with or without decreased adiposity indicating a pathogenic role of inflammatory immune reactivity [ , , ].
However, most studies do not allow to distinguish between effects mediated at the level of the liver, pancreas, vasculature, gut, brain, or adipose tissue. A detailed discussion of diet-induced inflammatory changes outside the visceral fat tissue and of immune intervention studies is outside the scope of this paper.
Inflammation of tissues in the absence of infectious, toxic or allergenic agents in general is caused by the local expression of immunostimulatory molecules in the context of metabolic or physical tissue damage. The activation of resident immune cells as well as the influx of immune cells from circulation into stressed tissue can be interpreted as an attempt to regain the previous physiological balance [ 2 , 74 ].
Loss of structure tissue damage elicits a more intense form of inflammation with influx of circulating immune cells, again primarily supporting tissue functions [ 2 ].
In obese visceral fat tissue, adaptive or repair functions of macrophages and other activated immune cells include support of matrix remodeling and angiogenesis by secretion of proteases and growth factors to accommodate for adipocyte enlargement and hyperplasia, lipid uptake and catabolism to lower lipid load, stimulation of thermogenesis for lipid burning, promotion of lipolysis and local insulin resistance to reduce lipid storage, and clearance from dead adipocytes and senescent cells.
Concomitant fibrosis may be regarded as protective or detrimental, and a low density of senescent cells may favor matrix remodeling. The increase of crown-like structures and the accumulation of senescent cells suggest that repair functions become overwhelmed.
Whether pro-inflammatory activities carried by the immune cell infiltrate from circulation eventually contribute to tissue damage remains to be analyzed. Finally, subtypes of visceral obesity remain to be defined, and not all of them may be represented by animal models.
Subtypes may differ with respect to metabolic characteristics, age, sex or genetic background. The protective versus detrimental functions of inflammation may differ between subtypes.
Only articles published in English were selected. Chen L, Deng H, Cui H, Fang J, Zuo Z, Deng J, et al. Inflammatory responses and inflammation-associated diseases in organs.
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FEBS J. Weinstock A, Brown EJ, Garabedian ML, Pena S, Sharma M, Lafaille J, et al. Single-Cell RNA Sequencing of Visceral Adipose Tissue Leukocytes Reveals that Caloric Restriction Following Obesity Promotes the Accumulation of a Distinct Macrophage Population with Features of Phagocytic Cells.
Schipper HS, Prakken B, Kalkhoven E, Boes M. Adipose tissue-resident immune cells: key players in immunometabolism. Trends Endocrinol Metab.
Xu X, Grijalva A, Skowronski A, van EM SMJ, Ferrante AW Jr. Obesity activates a program of lysosomal-dependent lipid metabolism in adipose tissue macrophages independently of classic activation. Cell Metab. Jaitin DA, Adlung L, Thaiss CA, Weiner A, Li B, Descamps H, et al.
Lipid-Associated Macrophages Control Metabolic Homeostasis in a Trem2-Dependent Manner. Wang Q, Li D, Cao G, Shi Q, Zhu J, Zhang M, et al. IL signalling promotes adipocyte thermogenesis and energy expenditure.
Rahman MS, Jun H. The Adipose Tissue Macrophages Central to Adaptive Thermoregulation. Front Immunol. Backdahl J, Franzen L, Massier L, Li Q, Jalkanen J, Gao H, et al. Spatial mapping reveals human adipocyte subpopulations with distinct sensitivities to insulin.
Brestoff JR, Kim BS, Saenz SA, Stine RR, Monticelli LA, Sonnenberg GF, et al. Group 2 innate lymphoid cells promote beiging of white adipose tissue and limit obesity.
Painter JD, Akbari O. Type 2 Innate Lymphoid Cells: Protectors in Type 2 Diabetes. Macdougall CE, Wood EG, Loschko J, Scagliotti V, Cassidy FC, Robinson ME, et al. Visceral Adipose Tissue Immune Homeostasis Is Regulated by the Crosstalk between Adipocytes and Dendritic Cell Subsets.
According to the Harvard T. However, you can figure out your waist-to-hip ratio WHR at home or ask your healthcare provider to determine this measurement for you. According to a report by the World Health Organization WHO , citing a study , a waist-to-hip ratio above.
According to a study , the WHtR is particularly useful for people with type 1 diabetes. Researchers found that having a high WHtR was one of the best indicators that a person with type 1 diabetes also has a high percentage of visceral fat.
It was considered a more reliable metric than the WHR, body mass index BMI , and a body shape index ABSI. Having a larger waist circumference was also strongly associated with a high visceral fat percentage. To calculate your WHtR at home, simply divide your waist circumference by your height.
You can measure in either inches or in centimeters, as long as you measure your waist and height with the same units. An ideal WHtR is typically no greater than. Research has found that visceral fat contributes to insulin resistance. Visceral fat can also raise blood pressure quickly. Most importantly, carrying excess visceral fat increases your risk for developing several serious and life threatening medical conditions.
These include:. When possible, exercise for at least 30 minutes every day. Make sure to include both cardio exercises and strength training. Strength training will slowly burn more calories over time as your muscles get stronger and consume more energy. As often as possible, eliminate processed , high sugar foods from your diet and include more lean proteins , vegetables , and complex carbs , such as sweet potatoes , beans , and lentils.
Low carb diets , such as the keto diet , may also help you lose visceral fat. Discover other ways to reduce visceral fat. The stress hormone cortisol can actually increase how much visceral fat your body stores, so reducing the stress in your life will help make it easier to lose the fat.
Practice meditation , deep breathing , and other stress management tactics. Your doctor can use tests such as blood tests or an electrocardiogram ECG or EKG to check for health risks associated with high incidence of visceral fat.
They may also refer you to a nutritionist. That makes it that much more dangerous. Maintaining a healthy, active, low-stress lifestyle can help prevent visceral fat from building up in excess in the abdominal cavity.
The trouble with belly fat is that it's not limited to the layer of padding just below the skin. That's called subcutaneous fat. Belly fat also includes visceral fat. And that lies deep inside the abdomen and surrounds the internal organs.
People who regularly eat and drink more calories than they burn each day are more likely to gain extra weight, including belly fat. Getting older also makes a difference.
People lose muscle as they age. And the problem is worse for those who are not physically active. Loss of muscle mass decreases how quickly the body uses calories.
That can make it more challenging to maintain a healthy weight. For example, when men are in their 50s, they need about fewer calories a day than they do when they are in their 30s. Genes can contribute to an individual's chances of being overweight or obese too.
It also plays a role in where the body stores fat. Drinking alcohol can lead to what's sometimes called a beer belly, but beer alone isn't to blame. Drinking too much alcohol of any kind can add to the problem.
If you drink alcohol, do so only in moderation. For men, that means up to two drinks a day. The less a person drinks, the fewer calories, and the less likely belly fat will build up over time.
For men, a waist measurement of more than 40 inches centimeters signals an unhealthy amount of belly fat and a higher risk of health problems. In general, though, the greater the waist measurement, the higher the health risks.
You can strengthen and tone abdominal muscles with crunches or other exercises focused on your belly. But doing those exercises alone won't get rid of belly fat. The good news is that visceral fat responds to the same diet and exercise strategies that can help get rid of other extra pounds and lower total body fat.
Try these tips:. Losing belly fat takes effort and patience. To lose extra fat and keep it from coming back, aim for slow and steady weight loss. Ask your health care provider for help getting started and staying on track. There is a problem with information submitted for this request.
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Visceral fat and obesity excess of obsity fat can, obseity, have potentially faf consequences. Because obssity fat is in the abdominal Viscegal, Visceral fat and obesity is close to many vital Vieceral, such as the Visderal, Visceral fat and obesity, Ribose sugar and respiratory health intestines. The higher fag amount of visceral fat a person stores, the more at risk they are for certain health complications, such as type 2 diabetes and heart disease. Imaging scans, such as computed tomography CT or magnetic resonance imaging MRI scans are the most accurate way to determine whether someone has visceral fat. However, because conducting these scans is both expensive and time-consuming, a doctor is more likely to diagnose visceral fat by asking a person questions about their diet and lifestyle. Another useful way to determine how much visceral fat a person is carrying is to measure the size of their waist. A woman whose waist measures 35 inches or more is likely to have excess visceral fat.
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