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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Poussin
Carine
C
Center for Integrative Genomics and Department of Physiology, University of Lausanne, Lausanne, Switzerland.
Hall
Diana
D
Minehira
Kaori
K
Galzin
Anne-Marie
AM
Tarussio
David
D
Thorens
Bernard
B
D050153:Abdominal Fat / Q000378:metabolism*; D017667:Adipocytes / Q000187:drug effects; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D063387:Cannabinoid Receptor Antagonists; D004041:Dietary Fats / Q000008:administration & dosage; D005109:Extracellular Matrix / Q000378:metabolism*; D005786:Gene Expression Regulation; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000235:genetics* / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D000077285:Rimonabant; D050151:Subcutaneous Fat / Q000378:metabolism*; D014158:Transcription, Genetic
D001786:Blood Glucose; D063387:Cannabinoid Receptor Antagonists; D004041:Dietary Fats; D007328:Insulin; D020738:Leptin; D008079:Lipoproteins, VLDL; D010880:Piperidines; D011720:Pyrazoles; D000077285:Rimonabant