BACKGROUND: Quercetin is a promising phytochemical in treating abnormalities associated with metabolic syndrome (MetS). This study aimed to explore the morphometric, metabolic, transcriptomic, and nutrigenetic responses to quercetin supplementation using two genetically distinct MetS models that only differ in the variant of the MetS-related Zbtb16 gene (Zinc Finger And BTB Domain Containing 16). RESULTS: Quercetin supplementation led to a significant reduction in the relative weight of retroperitoneal adipose tissue in both investigated strains. A decrease in visceral (epididymal) fat mass, accompanied by an increase in brown fat mass after quercetin treatment, was observed exclusively in the SHR strain. While the levels of serum triglycerides decreased within both strains, the free fatty acids levels decreased in SHR-Zbtb16-Q rats only. The total serum cholesterol levels were not affected by quercetin in either of the two tested strains. While there were no significant changes in brown adipose tissue transcriptome, quercetin supplementation led to a pronounced gene expression shift in white retroperitoneal adipose tissue, particularly in SHR-Zbtb16-Q. CONCLUSION: Quercetin administration ameliorates certain MetS-related features; however, the efficacy of the treatment exhibits subtle variations depending on the specific variant of the Zbtb16 gene.

• Keywords
• Cholesterol, Metabolic syndrome, Quercetin, Rats, Retroperitoneal fat, ZBTB16,
• Publication type
• Journal Article MeSH

Quercetin, a flavonoid present in many fruits and vegetables, exhibits beneficial effects toward abnormalities related to metabolic syndrome. In this study, to further investigate metabolic and transcriptomic responses to quercetin supplementation, we used a genetic model of metabolic syndrome. Adult male rats of the PD/Cub strain were fed either a high-sucrose diet (HSD; control PD rats) or HSD fortified with quercetin (10 g quercetin/kg diet; PD-Q rats). Morphometric and metabolic parameters, along with transcriptomic profiles of the liver 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 Pparg, Adipoq, Nos2, and Mir378. In conclusion, quercetin supplementation improves abnormalities related to metabolic syndrome, namely adiposity, dyslipidemia and glucose intolerance.

• Keywords
• glucose intolerance, insulin, metabolic syndrome, quercetin, retroperitoneal fat, triglycerides,
• Publication type
• Journal Article MeSH

Several corresponding regions of human and mammalian genomes have been shown to affect sensitivity to the manifestation of metabolic syndrome via nutrigenetic interactions. In this study, we assessed the effect of sucrose administration in a newly established congenic strain BN.SHR20, in which a limited segment of rat chromosome 20 from a metabolic syndrome model, spontaneously hypertensive rat (SHR), was introgressed into Brown Norway (BN) genomic background. We mapped the extent of the differential segment and compared the genomic sequences of BN vs. SHR within the segment in silico. The differential segment of SHR origin in BN.SHR20 spans about 9 Mb of the telomeric portion of the short arm of chromosome 20. We identified non-synonymous mutations e.g., in ApoM, Notch4, Slc39a7, Smim29 genes and other variations in or near genes associated with metabolic syndrome in human genome-wide association studies. Male rats of BN and BN.SHR20 strains were fed a standard diet for 18 weeks (control groups) or 16 weeks of standard diet followed by 14 days of high-sucrose diet (HSD). We assessed the morphometric and metabolic profiles of all groups. Adiposity significantly increased only in BN.SHR20 after HSD. Fasting glycemia and the glucose levels during the oral glucose tolerance test were higher in BN.SHR20 than in BN groups, while insulin levels were comparable. The fasting levels of triacylglycerols were the highest in sucrose-fed BN.SHR20, both compared to the sucrose-fed BN and the control BN.SHR20. The non-esterified fatty acids and total cholesterol concentrations were higher in BN.SHR20 compared to their respective BN groups, and the HSD elicited an increase in non-esterified fatty acids only in BN.SHR20. In a new genetically defined model, we have isolated a limited genomic region involved in nutrigenetic sensitization to sucrose-induced metabolic disturbances.

• Keywords
• animal model, congenic rat, metabolic syndrome, nutrigenetics,
• MeSH
• Apolipoproteins M genetics   MeSH
• Genome-Wide Association Study MeSH
• Hypertension * metabolism   MeSH
• Rats MeSH
• Humans MeSH
• Chromosomes, Human, Pair 20 metabolism   MeSH
• Fatty Acids MeSH
• Metabolic Syndrome * genetics   metabolism   MeSH
• Nutrigenomics MeSH
• Fasting MeSH
• Rats, Inbred BN MeSH
• Rats, Inbred SHR MeSH
• Cation Transport Proteins * genetics   MeSH
• Sucrose adverse effects   MeSH
• Mammals genetics   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Apolipoproteins M MeSH
• Apom protein, rat MeSH Browser
• Fatty Acids MeSH
• Cation Transport Proteins * MeSH
• Sucrose MeSH
• SLC39A7 protein, human MeSH Browser