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.

• Klíčová slova
• Cholesterol, Metabolic syndrome, Quercetin, Rats, Retroperitoneal fat, ZBTB16,
• Publikační typ
• časopisecké články 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.

• Klíčová slova
• glucose intolerance, insulin, metabolic syndrome, quercetin, retroperitoneal fat, triglycerides,
• Publikační typ
• časopisecké články MeSH

Ellagic acid, a natural substance found in various fruits and nuts, was previously shown to exhibit beneficial effects towards metabolic syndrome. In this study, using a genetic rat model of metabolic syndrome, we aimed to further specify metabolic and transcriptomic responses to ellagic acid treatment. Adult male rats of the SHR-Zbtb16Lx/k.o. strain were fed a high-fat diet accompanied by daily intragastric gavage of ellagic acid (50 mg/kg body weight; high-fat diet-ellagic acid (HFD-EA) rats) or vehicle only (high-fat diet-control (HFD-CTL) rats). Morphometric and metabolic parameters, along with transcriptomic profile of liver and brown and epididymal adipose tissues, were assessed. HFD-EA rats showed higher relative weight of brown adipose tissue (BAT) and decreased weight of epididymal adipose tissue, although no change in total body weight was observed. Glucose area under the curve, serum insulin, and cholesterol levels, as well as the level of oxidative stress, were significantly lower in HFD-EA rats. The most differentially expressed transcripts reflecting the shift induced by ellagic acid were detected in BAT, showing downregulation of BAT activation markers Dio2 and Nr4a1 and upregulation of insulin-sensitizing gene Pla2g2a. Ellagic acid may provide a useful nutritional supplement to ameliorate features of metabolic syndrome, possibly by suppressing oxidative stress and its effects on brown adipose tissue.

• Klíčová slova
• brown adipose tissue, ellagic acid, insulin resistance, metabolic syndrome, oxidative stress,
• MeSH
• biologické markery analýza   MeSH
• dieta s vysokým obsahem tuků MeSH
• epididymis MeSH
• hnědá tuková tkáň chemie   MeSH
• játra chemie   MeSH
• krevní glukóza analýza   MeSH
• krysa rodu Rattus MeSH
• kyselina ellagová aplikace a dávkování   MeSH
• messenger RNA analýza   MeSH
• metabolický syndrom genetika   metabolismus   prevence a kontrola   MeSH
• oxidační stres účinky léků   MeSH
• potkani inbrední SHR MeSH
• RNA analýza   MeSH
• transkriptom účinky léků   MeSH
• tuková tkáň chemie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH
• krevní glukóza MeSH
• kyselina ellagová MeSH
• messenger RNA MeSH
• RNA MeSH

Overnutrition in pregnancy and lactation affects fetal and early postnatal development, which can result in metabolic disorders in adulthood. We tested a hypothesis that variation of the Zbtb16 gene, a significant energy metabolism regulator, modulates the effect of maternal high-sucrose diet (HSD) on metabolic and transcriptomic profiles of the offspring. We used the spontaneously hypertensive rat (SHR) strain and a minimal congenic rat strain SHR-Zbtb16, carrying the Zbtb16 gene allele originating from the PD/Cub rat, a metabolic syndrome model. Sixteen-week-old SHR and SHR-Zbtb16 rat dams were fed either standard diet (control groups) or a high-sucrose diet (HSD, 70% calories as sucrose) during pregnancy and 4 weeks of lactation. In dams of both strains, we observed an HSD-induced increase of cholesterol and triacylglycerol concentrations in VLDL particles and a decrease of cholesterol and triacylglycerols content in medium to very small LDL particles. In male offspring, exposure to maternal HSD substantially increased brown fat weight in both strains, decreased triglycerides in LDL particles, and impaired glucose tolerance exclusively in SHR. The transcriptome assessment revealed networks of transcripts reflecting the shifts induced by maternal HSD with major nodes including mir-126, Hsd11b1 in the brown adipose tissue, Pcsk9, Nr0b2 in the liver and Hsd11b1, Slc2a4 in white adipose tissue. In summary, maternal HSD feeding during pregnancy and lactation affected brown fat deposition and lipid metabolism in adult male offspring and induced major transcriptome shifts in liver, white, and brown adipose tissues. The Zbtb16 variation present in the SHR-Zbtb16 led to several strain-specific effects of the maternal HSD, particularly the transcriptomic profile shifts of the adult male offspring.

• Klíčová slova
• DOHAD, Zbtb16, high-sucrose diet, maternal nutrition, transcriptomics,
• Publikační typ
• časopisecké články MeSH

Both prenatal and postnatal excessive consumption of dietary sucrose or fructose was shown to be detrimental to health and contributing to pathogenesis of metabolic syndrome. Our knowledge of genetic determinants of individual sensitivity to sucrose-driven metabolic effects is limited. In this study, we have tested the hypothesis that a variation of metabolic syndrome-related gene, Zbtb16 (Zinc Finger and BTB Domain Containing 16 will affect the reaction to high-sucrose diet (HSD) content in "matched" nutritional exposition settings, i.e. maternal HSD with re-exposition to HSD in adulthood vs. standard diet. We compared metabolic profiles of adult males of spontaneously hypertensive rats (SHR) and a single-gene, minimal congenic strain SHR-Zbtb16 fed either standard diet or exposed to HSD prenatally throughout gestation and nursing and again at the age of 6 months for the period of 14 days. HSD exposition led to increased adiposity in both strains and decrease of glucose tolerance and cholesterol (Ch) concentrations in majority of low-density lipoprotein (LDL) particle classes and in very large and large high-density lipoprotein (HDL) in SHR-Zbtb16 male offspring. There was a similar pattern of HSD-induced increase of triacylglycerols in chylomicrons and very low-density lipoprotein (VLDL) of both strains, though the increase of (triacylglycerol) TAG content was clearly more pronounced in SHR. We observed significant STRAIN*DIET interactions for the smallest LDL particles as their TAG content decreased in SHR-Zbtb16 and did not change in SHR in response to HSD. In summary, we provide evidence of nutrigenetic interaction between Zbtb16 and HSD in context of pathogenesis of metabolic syndrome.

• MeSH
• cholesterol metabolismus   MeSH
• hypertenze genetika   metabolismus   MeSH
• konzumní sacharóza metabolismus   MeSH
• krysa rodu Rattus MeSH
• metabolický syndrom etiologie   metabolismus   patologie   MeSH
• modely nemocí na zvířatech MeSH
• nutrigenomika metody   MeSH
• potkani inbrední SHR MeSH
• protein promyelocytické leukemie s motivem zinkového prstu genetika   metabolismus   MeSH
• sladidla metabolismus   MeSH
• těhotenství MeSH
• triglyceridy metabolismus   MeSH
• zvířata kongenní MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cholesterol MeSH
• konzumní sacharóza MeSH
• protein promyelocytické leukemie s motivem zinkového prstu MeSH
• sladidla MeSH
• triglyceridy MeSH
• ZBTB16 protein, rat MeSH Prohlížeč

BACKGROUND: Glucocorticoids (GCs) are potent therapeutic agents frequently used for treatment of number of conditions, including hematologic, inflammatory, and allergic diseases. Both their therapeutic and adverse effects display significant interindividual variation, partially attributable to genetic factors. We have previously isolated a seven-gene region of rat chromosome 8 sensitizing to dexamethasone (DEX)-induced dyslipidemia and insulin resistance (IR) of skeletal muscle. Using two newly derived congenic strains, we aimed to investigate the effect of one of the prime candidates for this pharmacogenetic interaction, the Zbtb16 gene. METHODS: Adult male rats of SHR-Lx.PD5PD-Zbtb16 (n = 9) and SHR-Lx.PD5SHR-Zbtb16 (n = 8) were fed standard diet (STD) and subsequently treated with DEX in drinking water (2.6 µg/ml) for 3 days. The morphometric and metabolic profiles of both strains including oral glucose tolerance test, triacylglycerols (TGs), free fatty acids, insulin, and C-reactive protein levels were assessed before and after the DEX treatment. Insulin sensitivity of skeletal muscle and visceral adipose tissue was determined by incorporation of radioactively labeled glucose. RESULTS: The differential segment of SHR-Lx.PD5SHR-Zbtb16 rat strain spans 563 kb and contains six genes: Htr3a, Htr3b, Usp28, Zw10, Tmprss5, and part of Drd2. The SHR-Lx.PD5PD-Zbtb16 minimal congenic strain contains only Zbtb16 gene on SHR genomic background and its differential segment spans 254 kb. Total body weight was significantly increased in SHR-Lx.PD5PD-Zbtb16 strain compared with SHR-Lx.PD5SHR-Zbtb16 , however, no differences in the weights of adipose tissue depots were observed. While STD-fed rats of both strains did not show major differences in their metabolic profiles, after DEX treatment the SHR-Lx.PD5PD-Zbtb16 congenic strain showed increased levels of TGs, glucose, and blunted inhibition of lipolysis by insulin. Both basal and insulin-stimulated incorporation of radioactively labeled glucose into skeletal muscle glycogen were significantly reduced in SHR-Lx.PD5PD-Zbtb16 strain, but the insulin sensitivity of adipose tissue was comparable between the two strains. CONCLUSION: The metabolic disturbances including impaired glucose tolerance, dyslipidemia, and IR of skeletal muscle observed after DEX treatment in the congenic SHR-Lx.PD5PD-Zbtb16 reveal the Zbtb16 locus as a possible sensitizing factor for side effects of GC therapy.

• Klíčová slova
• ZBTB16, congenic strain, dexamethasone, insulin resistance, pharmacogenetics and pharmacogenomics, rat models,
• Publikační typ
• časopisecké články MeSH