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Transcriptomic of Visceral Adipose Tissue in HFD-induced obesity: evaluation of Resveratrol

ABSTRACT: Visceral adipose tissue (VAT) expansion during the development of obesity is a hallmark of metabolic syndrome, characterized by hypoxia, oxidative stress, and a shift toward a pro-inflammatory secretome. This series examines the transcriptomic profile of VAT in male C57BL/6 mice subjected to long-term obesity induced by a high-fat diet (HFD, 60% of kcal from fat). To investigate new therapeutic avenues, we evaluated the impact of daily resveratrol administration (2.25 mg/kg) for 28 days, beginning at week 16 of life (8 weeks on the HFD diet). Using a transcriptomic approach (RNA-seq), we mapped the expression changes associated with the transition from healthy to dysfunctional adipose tissue. This study provides a detailed molecular resource for understanding how obesity-induced adipocyte stress can be attenuated by natural bioactives.

ORGANISM(S): Mus musculus

PROVIDER: GSE329568 | GEO | 2026/05/04

REPOSITORIES: GEO

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Project description:High fat diet (HFD) during early development may increase the susceptibility to metabolic diseases later in life. Adipose tissue is an important regulator of energy metabolism through secretion of endocrine and paracrine/autocrine factors. In the present study we first screened the expression profiles of about 500 miRNAs in visceral white adipose tissue (VAT) from mice fed a control diet (CD) and mice fed a matched HFD during three different life stages i) in utero (UT), ii) in utero and lactation (UL), iii) in utero until termination at age 23 weeks (WL). Fourteen differentially expressed miRNAs were identified and these miRNAs were used for prediction of targeted signalling pathways. In addition, analysis of high abundance miRNAs showed a marked downregulation of the miR-200 family members in the UT group. Subsequently, the transcript levels of 89 selected genes represented in the predicted signalling pathways were determined. Six genes (Deptor, Il6, Irs1, lep, Lpin1 and prkaa1) showed a significant differential expression due to HFD feeding compared to controls, and HFD treatment had significant effects on the WL-groups. The expression pattern of Deptor, Il6, Irs1, Lep genes showed a similar direction of change across all HFD treatment groups. The differential expression of Irs1 and Deptor genes points to a persistent modification of the insulin receptor – mTOR signalling network. This finding is supported by increased serum insulin and IGF-1 levels and impaired glucose regulation in the HFD groups. This study shows that developmental HFD can lead to persistent changes in VAT miRNA expression levels that is associated with a modification of key signalling pathways regulating energy metabolism also in animals with normal BMI.dy we have screened over 500 miRNAs for differential expression in visceral white adipose tissue (vWAT) between mice fed a control diet (CD; 10% kcal from fat) and mice fed a matched high fat diet (HFD; 45% kcal from fat) during three different life stages i) in utero (UT), ii) in utero and lactation (UL), iii) in utero until termination (WL). All animals were sacrifices at an age of 23 weeks.

Project description:Thoracic perivascular adipose tissue (PVAT) is a unique adipose depot that likely influences vascular function and susceptibility to pathogenesis in obesity and metabolic syndrome. Surprisingly, PVAT has been reported to share characteristics of both brown and white adipose, but a detailed direct comparison to interscapular brown adipose tissue (BAT) has not been performed. Here we show by full genome DNA microarray analysis that global gene expression profiles of PVAT are virtually identical to BAT, with equally high expression of Ucp-1, Cidea and other genes known to be uniquely or very highly expressed in BAT. PVAT and BAT also displayed nearly identical phenotypes upon immunohistochemical analysis, and electron microscopy confirmed that PVAT contained multilocular lipid droplets and abundant mitochondria. Compared to white adipose tissue (WAT), PVAT and BAT from C57BL/6 mice fed a high fat diet for 13 weeks had markedly lower expression of immune cell-enriched mRNAs, suggesting resistance to obesity-induced inflammation. Indeed, staining of BAT and PVAT for macrophage markers (F4/80, CD68) in obese mice showed virtually no macrophage infiltration, and FACS analysis of BAT confirmed the presence of very few CD11b+/CD11c+ macrophages in BAT (1.0%) in comparison to WAT (31%). In summary, murine PVAT from the thoracic aorta is virtually identical to interscapular BAT, is resistant to diet-induced macrophage infiltration, and thus may play an important role in protecting the vascular bed from thermal and inflammatory stress. 8-week-old male C57BL6/J mice were fed a normal (ND) or high fat diet (HFD) (Research Diets 12451, 45 kcal% fat) for 13 weeks. Mice were then euthanized and four different adipose depots were harvested for RNA analysis: perivascular fat from the lesser curvature of the aortic arch (PVAT), interscapular brown adipose (BAT), inguinal adipose tissue (SAT), and epididymal adipose tissue (VAT). 250 ng total RNA pooled from two mice was used for cDNA synthesis; 3 biological replicates per tissue and diet were performed for a total of 24 hybridizations.

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Transcriptomic of Visceral Adipose Tissue in HFD-induced obesity: evaluation of Resveratrol

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