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Different transcriptional control of metabolism and extracellular matrix in visceral and subcutaneous fat of obese and rimonabant treated mice.

ABSTRACT: The visceral (VAT) and subcutaneous (SCAT) adipose tissues play different roles in physiology and obesity. The molecular mechanisms underlying their expansion in obesity and following body weight reduction are poorly defined.C57Bl/6 mice fed a high fat diet (HFD) for 6 months developed low, medium, or high body weight as compared to normal chow fed mice. Mice from each groups were then treated with the cannabinoid receptor 1 antagonist rimonabant or vehicle for 24 days to normalize their body weight. Transcriptomic data for visceral and subcutaneous adipose tissues from each group of mice were obtained and analyzed to identify: i) genes regulated by HFD irrespective of body weight, ii) genes whose expression correlated with body weight, iii) the biological processes activated in each tissue using gene set enrichment analysis (GSEA), iv) the transcriptional programs affected by rimonabant.In VAT, "metabolic" genes encoding enzymes for lipid and steroid biosynthesis and glucose catabolism were down-regulated irrespective of body weight whereas "structure" genes controlling cell architecture and tissue remodeling had expression levels correlated with body weight. In SCAT, the identified "metabolic" and "structure" genes were mostly different from those identified in VAT and were regulated irrespective of body weight. GSEA indicated active adipogenesis in both tissues but a more prominent involvement of tissue stroma in VAT than in SCAT. Rimonabant treatment normalized most gene expression but further reduced oxidative phosphorylation gene expression in SCAT but not in VAT.VAT and SCAT show strikingly different gene expression programs in response to high fat diet and rimonabant treatment. Our results may lead to identification of therapeutic targets acting on specific fat depots to control obesity.

SUBMITTER: Poussin C

PROVIDER: S-EPMC2586343 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

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Different transcriptional control of metabolism and extracellular matrix in visceral and subcutaneous fat of obese and rimonabant treated mice.

Poussin Carine C Hall Diana D Minehira Kaori K Galzin Anne-Marie AM Tarussio David D Thorens Bernard B

PloS one 20080101 10

<h4>Background</h4>The visceral (VAT) and subcutaneous (SCAT) adipose tissues play different roles in physiology and obesity. The molecular mechanisms underlying their expansion in obesity and following body weight reduction are poorly defined.<h4>Methodology</h4>C57Bl/6 mice fed a high fat diet (HFD) for 6 months developed low, medium, or high body weight as compared to normal chow fed mice. Mice from each groups were then treated with the cannabinoid receptor 1 antagonist rimonabant or vehicle ...[more]

PMID: 19030233

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Project description:Nonalcoholic fatty liver disease (NAFLD) has become the most common cause of liver disease affecting 20-30% of the population in developed countries. NAFLD is strongly associated with abdominal obesity and is recognized as the hepatic manifestation of the metabolic syndrome. In a subgroup of patients with NAFLD inflammation and fibrosis develops, this so-called Non-Alcoholic Steatohepatitis (NASH) may progress to cirrhosis and hepatocellular carcinoma. A multi-hit hypothesis has been proposed in which during the first “hit” fat accumulation occurs in hepatocytes from excessive delivery of fatty acids from adipose tissue, in addition there is an imbalance in lipid synthesis and export. However, the reason why fat accumulation is subsequently followed by inflammation and fibrosis in some patients is poorly understood. We studied the role of inflammatory processes in visceral and subcutaneous fat at the transcriptional level using microarray in bariatric patients from whom the liver histology was available. Patients scheduled for bariatric surgery were recruited in two centers (Pretoria/South-Africa and Antwerpen/Belgium). At the time of the procedure, tissue samples of the visceral and subcutaneous fat were taken for molecular analysis as well as liver tissue for histology, also full biochemical data was collected. Patients were grouped according histology: group I (<5% steatosis), group II (NAFLD, 30-50% steatosis), group III (NASH) and group IV (NASH + fibrosis F2-F3). The following samples were used for microarray (number of 'patients' respectively for stages I-II-III-IV): visceral fat (9-7-7-5), subcutaneous fat (6-6-6-5). Microarrays were run in two batches (15xxx versus 17xxx CEL file samples; indicated in the description field). Samples from two patients (FN61; FN76) were put twice on array (15078+17881; 15064+17877) to verify and exclude batch effects. Please note that, due to technical repeats with two patient samples, the number of 'visceral fat samples' for stages I-II-III-IV is 10-7-8-5.

Dataset Information

Different transcriptional control of metabolism and extracellular matrix in visceral and subcutaneous fat of obese and rimonabant treated mice.

Publications

Different transcriptional control of metabolism and extracellular matrix in visceral and subcutaneous fat of obese and rimonabant treated mice.

Similar Datasets

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