Quercetin and weight loss -
This suggests that Cyp2b9 expression can be a marker in a possible common mode of action of the flavonoids. It is tempting to speculate that the newly observed common effects of the flavonoids on hepatic Cyp2b9 expression and adiposity are mechanistically related, but this requires further investigation, as is the possible impact of the polymorphic CYP2B6 enzyme on CVD preventive lipid lowering effects of flavonoids.
Of all studied flavonoids, quercetin showed the strongest lowering effects on HF-induced parameters. Quercetin not only affected most parameters, but also showed the most prominent effects. This is supported by correlation analysis Fig.
It is particularly illustrated by the correlation plot of leptin versus body weight gain Fig. This is especially of interest given that leptin, known to regulate body weight gain, can be measured easily and rapidly in circulation.
This positions leptin as a potential practical and useful marker to quantify flavonoid effects on HF-induced adiposity, to be used in animal as well as human studies. In humans, the estimated intake of these individual flavonoids via food is between 0.
The levels used in this experiment are comparable with levels used in animal studies; however, for further research it would be interesting to elaborate if lower doses can also be effective. We have investigated the effects of individual flavonoids. However, in our daily diet a mixture of flavonoids will be present.
In theory flavonoids could act in an additive or synergistic way, the latter for example due to their influence on efflux transporters. Furthermore, the dietary context could also influence the effects of flavonoids Bohn ; Hoek-van den Hil et al.
In conclusion, a direct comparison of metabolic effects of quercetin, hesperetin, epicatechin, apigenin and anthocyanins indicated that all flavonoids beneficially affected HF-induced disturbance of whole-body energy balance and lipid handling, with serum leptin levels as a sensitive marker.
This confirms the suggested potential of these flavonoids in lowering CVD risk factors. Furthermore, the reduction in hepatic Cyp2b9 transcript levels was shown for all flavonoids.
Overall, quercetin appeared to be the most potent flavonoid in preventing HF-induced effects. Benavente-Garcia O, Castillo J Update on uses and properties of citrus flavonoids: new findings in anticancer, cardiovascular, and anti-inflammatory activity.
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We thank Kristian Larsen for his kind gift of anthocyanins Medox and our colleagues from the animal facilities and Jovita Pranowo and Lisa Hoving for their practical help.
HAP is a member of the European Union COST Action FA POSITIVe. Elise F. Hoek-van den Hil, Evert M. van Schothorst, Inge van der Stelt, Hans J. Swarts, Marjanne van Vliet, Tom Amolo, Jacques J.
Vervoort, Dini Venema, Peter C. Hollman, Ivonne M. Rietjens and Jaap Keijer declare that they have no conflict of interest. All institutional and national guidelines for the care and use of laboratory animals were followed.
Human and Animal Physiology, Wageningen University, Wageningen, The Netherlands. Division of Toxicology, Wageningen University, Wageningen, The Netherlands. Laboratory of Biochemistry, Wageningen University, Wageningen, The Netherlands. You can also search for this author in PubMed Google Scholar.
Correspondence to Evert M. van Schothorst. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.
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Genes Nutr 10 , 23 Download citation. Received : 18 February Accepted : 08 May Published : 29 May Anyone you share the following link with will be able to read this content:.
Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content. Search all BMC articles Search. Download PDF. Research Paper Open access Published: 29 May Direct comparison of metabolic health effects of the flavonoids quercetin, hesperetin, epicatechin, apigenin and anthocyanins in high-fat-diet-fed mice Elise F.
Hoek-van den Hil 1 , 2 , 3 , Evert M. van Schothorst 1 , Inge van der Stelt 1 , Hans J. Swarts 1 , Marjanne van Vliet 1 , Tom Amolo 1 , Jacques J. Vervoort 4 , Dini Venema 3 , Peter C.
Hollman 3 , Ivonne M. Abstract Dietary flavonoid intake is associated with reduced risk of cardiovascular diseases, possibly by affecting metabolic health.
Introduction Fruit and vegetable consumption is regarded as protective against cardiovascular diseases CVD Estruch et al. HPLC analysis of flavonoid levels in serum and diet Flavonoid levels in serum were measured using HPLC with coulometric array detection as described Hoek-van den Hil et al.
Energy content of faeces and diet Bomb calorimetry was used to determine energy content of diet and faeces Calorimeter C, IKA, Staufen, Germany as described Hoek-van den Hil et al.
Indirect calorimetric and activity measurements Indirect calorimetry and activity were measured in weeks 1, 5 and Motor performance Balance and motor coordination was assessed by Rotarod IITC Life Science, Woodland Hills, USA in week 9. Lipid determination in serum and liver Because flavonoids were previously shown to interfere with commonly used commercially available enzymatic lipid assays Hoek-van den Hil et al.
RT-qPCR RNA from liver was isolated using RNeasy columns Qiagen, Venlo, The Netherlands , RNA from epiWAT was extracted with Trizol Invitrogen, Breda, The Netherlands , and quality was verified [as published Hoek-van den Hil et al.
Serum leptin levels Serum leptin levels were determined using a leptin ELISA kit Crystal Chem Inc. Histology of epididymal white adipose tissue Paraffin-embedded epididymal white adipose tissue epiWAT was cut into 5-µm sections and stained using Periodic Acid Schiff Haematoxylin PASH.
Body weight, metabolisable energy intake and feed efficiency Body weight was significantly increased due to HF compared with NF feeding during the whole intervention period, with a cumulative body weight gain of HF mice being four times higher than the weight gain of NF mice Fig.
Full size image. Table 1 Hepatic gene expression RT-qPCR Full size table. Table 2 Gene expression in white adipose tissue Full size table. References Benavente-Garcia O, Castillo J Update on uses and properties of citrus flavonoids: new findings in anticancer, cardiovascular, and anti-inflammatory activity.
Endocrinol Metab Clin North Am — Article CAS PubMed Central PubMed Google Scholar Bohn T Dietary factors affecting polyphenol bioavailability. Eur J Clin Nutr 51 Suppl 1 :S66—S69 PubMed Google Scholar Honkakoski P, Zelko I, Sueyoshi T, Negishi M The nuclear orphan receptor CAR-retinoid X receptor heterodimer activates the phenobarbital-responsive enhancer module of the CYP2B gene.
Mol Cell Biol — CAS PubMed Central PubMed Google Scholar Hooper L, Kroon PA, Rimm EB, Cohn JS, Harvey I, Le Cornu KA, Ryder JJ, Hall WL, Cassidy A Flavonoids, flavonoid-rich foods, and cardiovascular risk: a meta-analysis of randomized controlled trials.
Am J Clin Nutr —50 CAS PubMed Google Scholar Janssen K, Mensink RP, Cox FJ, Harryvan JL, Hovenier R, Hollman PC, Katan MB Effects of the flavonoids quercetin and apigenin on hemostasis in healthy volunteers: results from an in vitro and a dietary supplement study.
Am J Clin Nutr — CAS PubMed Google Scholar Jung CH, Cho I, Ahn J, Jeon TI, Ha TY Quercetin reduces high-fat diet-induced fat accumulation in the liver by regulating lipid metabolism genes.
Am J Clin Nutr — CAS PubMed Google Scholar Manach C, Williamson G, Morand C, Scalbert A, Remesy C Bioavailability and bioefficacy of polyphenols in humans. Am J Clin Nutr S—S CAS PubMed Google Scholar Massaro M, Scoditti E, Carluccio MA, De Caterina R Nutraceuticals and prevention of atherosclerosis: focus on omega-3 polyunsaturated fatty acids and mediterranean diet polyphenols.
x Article CAS PubMed Google Scholar Mclean JA, Tobin G Animal and human calorimetry, 1st edn. Cambridge University Press, Cambridge Google Scholar Murano I, Barbatelli G, Parisani V, Latini C, Muzzonigro G, Castellucci M, Cinti S Dead adipocytes, detected as crown-like structures, are prevalent in visceral fat depots of genetically obese mice.
MJLR Article CAS PubMed Google Scholar Perez-Vizcaino F, Duarte J Flavonols and cardiovascular disease. Can J Sport Sci —29 CAS PubMed Google Scholar Peterson JJ, Dwyer JT, Jacques PF, McCullough ML Associations between flavonoids and cardiovascular disease incidence or mortality in European and US populations.
x Article PubMed Central PubMed Google Scholar Phung OJ, Baker WL, Matthews LJ, Lanosa M, Thorne A, Coleman CI Effect of green tea catechins with or without caffeine on anthropometric measures: a systematic review and meta-analysis.
Toxicol Sci — Article CAS PubMed Google Scholar Spencer JP Flavonoids and brain health: multiple effects underpinned by common mechanisms. Acknowledgments This research was financially supported by the graduate school VLAG and RIKILT.
Conflict of interest Elise F. Ethical standard All institutional and national guidelines for the care and use of laboratory animals were followed. Author information Authors and Affiliations Human and Animal Physiology, Wageningen University, Wageningen, The Netherlands Elise F.
Rietjens RIKILT Wageningen UR, Wageningen, The Netherlands Elise F. Hollman Laboratory of Biochemistry, Wageningen University, Wageningen, The Netherlands Jacques J. Vervoort Authors Elise F. Hoek-van den Hil View author publications. View author publications.
Electronic supplementary material. Supplementary material 1 PDF kb. This ability to target numerous components of MetS makes quercetin a highly potent agent offering a potentially effective treatment alternative or an add-on to standard pharmacotherapy 16 — In this study, we examined the effect of oral quercetin administration on morphometric and metabolic parameters associated with MetS as well as the transcriptomic profiles of the liver and retroperitoneal fat tissue.
For this purpose, we used an inbred rodent model of MetS that carries a variant in the Zbtb16 Zinc finger and BTB Domain Containing 16 gene that is known to modulate the propensity for features of MetS including adipogenesis, insulin sensitivity and dyslipidemia in both humans and rodent models 19 , The strain has not only been exploited as a genetic model of limb malformation 21 , 22 but was established as a model for MetS as it carries a variant in one of the metabolic syndrome-related genes, Zbtb16 23 , At all times, the animals were given free access to food and water.
Over the period of 2 weeks, the control group was fed a high-sucrose diet HSD, protein The dose of quercetin used here was chosen to be similar to the doses used in previous studies 16 , Bodyweight and food intake were measured twice a week for each group.
Blood samples for metabolic and glycemic assessments were drawn after overnight fasting from the tail vein. Blood glucose concentrations over the period of min were used to calculate the area under the curve.
All rats were then sacrificed and the weight of heart, liver, kidneys, adrenals, and brown, epididymal and retroperitoneal adipose tissue were determined. Biochemical parameters were determined as follows: serum total cholesterol and triglycerides concentrations using kits from Erba Lachema Brno, Czechia ; non-esterified fatty acids using kit from Roche Diagnostic Mannheim, Germany ; insulin using a rat insulin enzyme-linked immunosorbent assay kit Mercodia, Uppsala, Sweden and high-molecular weight HMW adiponectin using an ELISA kit MyBioSource, San Diego, CA, USA.
The resulting pellet was dissolved in isopropyl alcohol with the content of the triglycerides determined by enzymatic assay Erba-Lachema, Brno, Czechia. Total RNA was isolated from the liver and retroperitoneal fat RNeasy Mini Kit, Qiagen, Hilden, Germany.
Microarray experiments were performed using the Rat Gene 2. The quality control of the chips was performed using Affymetrix Expression Console software Affymetrix, Santa Clara, CA, USA.
Partek Genomics Suite 7 Partek, St. Louis, MO, USA was used for subsequent data analysis. After applying quality filters and data normalization by Robust Multichip Average RMA algorithm, the set of obtained differentially expressed probe sets was filtered by the false discovery rate FDR method that is implemented in Partek Genomics Suite 7 Partek, St.
Louis, MO, USA. Transcriptomic data were then processed by a sequence of analyses hierarchical clustering and principal component analysis, gene ontology, gene set enrichment, upstream regulator analysis, mechanistic networks, causal network analysis and downstream effects analysis using Ingenuity Pathway Analysis Qiagen.
The microarray data generated and analyzed during the current study are available in the ArrayExpress repository 1 under accession number E-MTAB To validate the gene expression data obtained by microarray, quantitative real-time PCR RT-qPCR was performed. The amount of 1 μg of total RNA was used to synthesize cDNA using oligo-dT primers and the SuperScript III reverse transcriptase Invitrogen, Carlsbad, CA, USA.
Cycle threshold Ct values were normalized by using glyceraldehydephosphate dehydrogenase Gapdh TaqMan chemistry, Applied Biosystems as a standard. Relative quantification was performed using the Livak method All statistical analyses were performed in Statistica data analysis software system , version The effects of quercetin on morphometric and metabolic parameters in PD and PD-Q rats are shown in Table 1.
The relative weights of the liver and kidneys did not differ between PD and PD-Q rats. However, we detected increased heart and adrenal glands weights in rats after quercetin treatment Table 1. In addition, PD-Q rats showed significantly lower relative weights of retroperitoneal and epididymal fat Figures 1A,B , while no change in the weight of brown fat mass was detected between PD and PD-Q rats.
Table 1. Effect of quercetin supplementation on morphometric and metabolic variables in male PD rats. Figure 1. Effect of quercetin supplementation on retroperitoneal A and epididymal fat B. PD, control rats; PD-Q, rats supplemented with quercetin; b.
The levels of fasting blood glucose did not differ between PD and PD-Q rats. However, during the oral glucose tolerance test, PD-Q rats showed lower blood glucose level at the th min Figure 2A.
Furthermore, a smaller area under the glycemic curve and decreased fasting insulin concentration were detected in the PD-Q rats in comparison to the control group Figures 2B,C.
Figure 2. Effect of quercetin supplementation on blood glucose levels during oral glucose tolerance test A , area under the curve [AUC, B ] and insulin levels C.
The levels of adiponectin and free fatty acids did not differ between PD and PD-Q rats. Although no changes were detected in the serum and the liver cholesterol Figure 3B , quercetin treatment significantly decreased the level of total triglycerides in the serum as well as in the liver tissue in PD-Q rats Figure 3A.
Figure 3. Effect of quercetin supplementation on the triglycerides A and cholesterol B levels in the serum and the liver tissue. PD, control rats; PD-Q, rats supplemented with quercetin. The list of all significantly differentially expressed transcripts in between PD and PD-Q rats in liver and retroperitoneal fat tissue is shown in Supplementary Tables 1A,B , respectively.
There was no overlapping transcript between the sets of differentially expressed genes between adipose tissue and liver. In the adipose tissue, out of 32 transcripts showing significantly higher expression in PD-Q compared to PD, the most upregulated one was glycoprotein M6A Gpm6a. On the other hand, only 16 transcripts were downregulated by quercetin, including microRNA, Stonin 1 Ston1 , or regulated endocrine specific protein 18 Resp The Diseases and Functions analysis pointed to the cellular processes in the adipose tissue most impacted by quercetin administration, mostly pertaining to the aspects of lipid metabolism, cell cycle, and the conditions relevant to metabolic syndrome overweight disorder, insulin resistance as shown in Figure 4.
The upstream regulator analysis revealed six potentially activated or inhibited nodes Supplementary Table 2A affecting multiple of the differentially expressed genes in the adipose tissue. In particular, activated peroxisome proliferator-activated receptor gamma Pparg , adiponectin Adipoq , and inhibited state of nuclear receptor subfamily 4 group A member 1 Nr4a1 formed a network consistent with the observed gene expression changes Figure 4.
Figure 4. Overrepresented diseases and biological functions based on the differentially expressed genes in retroperitoneal adipose tissue of quercetin-treated vs. control PD rats in liver top panel and retroperitoneal adipose tissue middle panel.
Bottom panel : Mechanistic network of predicted upstream regulators ADIPOQ, NR4A1, and PPARG based on the dataset of differentially expressed genes in retroperitoneal adipose tissue of control and quercetin-treated PD rats.
The quercetin effect on the expression of genes significantly differentially expressed is shown in shades of green downregulation, blue for the predicted state of upstream regulators or red upregulation.
All above analyses were performed using Ingenuity Pathways Analysis. The comparison of hepatic transcriptomes of PD and PD-Q rats revealed only 20 transcripts to be significantly differentially expressed between the two groups after adjusting for multiple comparisons.
Among the nine downregulated transcripts, the expression of zinc finger protein A Zfpa and tsukushi, small leucine rich proteoglycan Tsku were most reduced by quercetin, while the genes most induced in livers of PD-Q vs.
PD were ras homolog family member T1 Rhot1 and amidohydrolase domain containing 1 Amdhd1. The canonical pathway analysis did not reveal any overrepresented pathways in the liver based on the differentially expressed genes, most likely also due to their relatively low number.
The Diseases and Functions analysis showed that quercetin affected the processes related to hepatocyte morphology, metabolic syndrome, cell cycle, RNA post-transcriptional gene silencing, and fatty acid metabolism Figure 4. The upstream regulator analysis predicted inhibition of a proto-oncogene Ets1 and of microRNA Mir Supplementary Table 2B.
The expression of a selected subset of genes was validated by qPCR; in all cases, the differences in expression were corroborated Supplementary Figure 1. Metabolic syndrome MetS is a combination of cardiometabolic abnormalities, such as central obesity, hypertension, glucose intolerance and dyslipidemia, correlated with an increased risk for type 2 diabetes, cardiovascular disease, and all-cause mortality 2 , 3.
Quercetin, found naturally in numerous fruits and vegetables, is one of the most abundant flavonoids in the human diet Extensive evidence has demonstrated its favorable impact on human health, including various features of MetS, such as obesity, glucose intolerance and dyslipidemia In this study, we investigated the effects of quercetin on morphometric and metabolic parameters, as well as transcriptomic profiles in a highly inbred genetic rat model of MetS.
Even though the exact etiopathogenetic factors leading to the development of MetS remain to be elucidated, some investigators believe that an excess of abdominal visceral fat, being the most prevalent aspect of the syndrome, plays a major role in the process 3 , Quercetin has been previously shown to exert an anti-obesity effect due to its anti-inflammatory and antioxidant properties, thus decreasing abdominal fat mass and abdominal circumference 30 — Likewise, in our study rats supplemented with quercetin showed lower weights of retroperitoneal and epididymal fat mass, both of which are considered a visceral fat.
However, no changes in total body weight were detected between the two tested groups. Moreover, we detected an increased weights of the heart and adrenal tissues in quercetin treated rats compared to controls.
Individuals with increased visceral fat deposition also typically evince insulin resistance and hyperinsulinemia, resulting in impaired glucose tolerance 33 , In this study, we detected a significant decrease in the fasting insulin levels along with a lower postprandial blood glucose level at th min of the oral glucose tolerance test and smaller area under the glycemic curve in rats treated with quercetin.
All these findings were expected based on extensive evidence demonstrating strong antidiabetic effect of quercetin in both animals and humans 14 , 35 , In addition, some studies also described its possible beneficial effect in a prevention and treatment of long-term complications of diabetes, such as retinopathy, nephropathy, neuropathy, or atherosclerosis 36 — Furthermore, quercetin also protects pancreatic β-cells against damage, preserves their mass and function, and stimulates regeneration of β-cells 41 , Atherogenic dyslipidemia, namely high triglycerides and low HDL-cholesterol levels, is an integral component of MetS and a major risk factor for developing cardiovascular diseases 43 , Although quercetin seems to have a favorable effect toward normalizing blood lipid levels, the results are not consistent.
Many studies report very little or no improvement in lipid levels after quercetin administration 45 , In this study, we detected no significant changes in total cholesterol and free fatty acid levels.
However, the level of triglycerides TG greatly decreased in the serum as well as in the liver of rats treated with quercetin.
Some other studies also support these findings confirming the ability of quercetin to decrease TG levels, while total cholesterol levels remained unchanged or even increased at the end of the experimental period 46 , Further studies are needed to fully elucidate the effect of quercetin on blood lipids levels and its clinical relevance.
One of the most quercetin-downregulated genes in liver was tsukushi Tsku. It was identified as an inducible hepatokine, its deficiency protected mice from high-fat-diet-induced obesity and metabolic disorders and was connected with reduced adiposity 50 , similarly to the effects observed in quercetin-fed rats in this study.
While the exact function of the most downregulated hepatic gene, Zfpa , is not clear, it was found to have cis-expression quantitative trait locus eQTL and, at the same time, a significant correlation between its expression in liver or adipose tissue with hepatic TG levels in mouse model of hepatic steatosis Also, its hepatic expression increases after ethanol bolus Quercetin-fed rats had substantially increased expression of a mitochondrial Rho-GTPase, Rhot1 , crucial for mitochondrial trafficking and peroxisomal fission The nodes identified in upstream regulator analysis of the retroperitoneal adipose tissue transcriptome revealed the potentially beneficial shifts in gene expression.
There is ample evidence for the involvement of microRNAs in both pathogenesis of metabolic syndrome and the favorable action of quercetin and other polyphenols Here, the most downregulated transcript by quercetin in the adipose tissue is Mir , and in the liver, Mir was identified as an important inhibited upstream regulator.
The observed lower Mir expression may thus reflect the deceleration of the cell cycle in adipose tissue stem cells in the situation of quercetin-induced fat loss.
Mir is encoded within a master metabolic regulator, the peroxisome proliferator-activated receptor γ coactivator 1β PGC-1β , and mice lacking Mir were resistant to high-fat diet-induced obesity and exhibited enhanced mitochondrial fatty acid metabolism and elevated oxidative capacity of insulin-target tissues Together with the predicted upregulation of Adipoq , Pparg and Ppargc1 a and downregulation of Nos2 nodes, the overall transcriptome shift corresponds to a gene expression profile repeatedly associated with amelioration of insulin resistance 57 — This could represent the potential underlying mechanism of the observed insulin-sensitizing action in quercetin-treated rats.
The limitations of our study include the use of only adult male rats of a single inbred strain as sex-specific genetic architecture of MetS and its components The experimental design aimed to address the subtle effects of short-term quercetin administration, therefore, we opted to perform the experiment while maximizing the homogeneity of the experimental and control groups.
In addition, a single dose and regimen of quercetin administered to the model animals did not allow us to assess dosage-dependent effects.
Individual features of MetS, such as adiposity, glucose intolerance and blood triglycerides levels in rats can be ameliorated by quercetin. Here, we present crucial transcriptomic nodes and networks, through which the quercetin may effectuate its metabolic actions on liver and adipose tissue.
As the prevalence of MetS is still increasing, dietary supplementation with either purified quercetin or food rich in quercetin could potentially be an effective intervention strategy. The animal study was reviewed and approved by Ethics Committees of the First Faculty of Medicine of the Charles University.
AK and OŠ contributed to conception and design of the study and involved in data curation, statistical analysis, and funding acquisition. HM, IM, and MH carried out the metabolic profiling. AK and BC performed transcriptomic analysis and real-time PCR.
AK drafted the initial manuscript. OŠ, BC, HM, IM, and MH participated in writing—review and editing the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version. This research was funded by the Charles University in Prague GAUK and SVV and Ministry of Health, Czechia — conceptual development of research organization , General University Hospital in Prague, Czechia.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.
Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Tune JD, Goodwill AG, Sassoon DJ, Mather KJ.
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So: Quercetin is a polyphenolic nutrient compound known as a weigjt, a type of Herbal hunger control that also Quegcetin as an Post-workout nutrition for body composition. The Quercefin is commonly weighr in fruits and Plant-based enzymes such as Quercetin and weight loss, onions, capers, Herbal hunger control greens, and tomatoes. Most people get their Quercetin from apples and potatoes. On top of this, several studies have found that organically-grown fruit and veg tends to contain more Quercetin than those that are grown conventionally. What are your body goals? Quercetin is understood to help reduce inflammation in the body. The compound may play a role in the inhibition of cytokines, a type of cell that promotes inflammation. Quercetin, a flavonoid present in many Quercetij and vegetables, Anti-cancer charities beneficial effects toward abnormalities related to metabolic syndrome. In this Essential oil safety, Herbal hunger control further investigate metabolic and Quercetin and weight loss responses to quercetin Quefcetin, we used ewight genetic model of metabolic Quercetin and weight loss. Morphometric and weiyht parameters, along with weighf profiles Boosts mental precision Quercetin and weight loss Quefcetin and retroperitoneal fat, were assessed. The relative weights of epididymal and retroperitoneal fat were significantly decreased in quercetin-treated animals. Furthermore, a smaller area under the glycemic curve along with a decreased level of fasting insulin were detected in PD-Q rats. While no changes in total cholesterol levels were observed, the overall level of triglycerides decreased in the serum and the liver of the PD-Q rats. The transcriptomic profile of the liver and the adipose tissue corroborated the metabolic and morphometric findings, revealing the pattern consistent with insulin-sensitizing changes, with major regulator nodes being PpargAdipoqNos2and Mir
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