The PPARgamma ligand rosiglitazone influences triacylglycerol metabolism in non-obese males, without increasing the transcriptional activity of PPARgamma in the subcutaneous adipose tissue.
PPARgamma is obligatory for fat mass generation and is thought to determine the amount of TAG stored per fat cell. We investigated whether ligand availability for PPARgamma is rate limiting in fat mass generation and substrate metabolism. Twenty healthy men (20-29 years) were randomly assigned to receive the PPARgamma ligand rosiglitazone (RSG) (8 mg/d) (n 10) or a placebo (n 10) during a stay of 7 d in a respiration chamber. Food intake was ad libitum, resulting in positive energy balances of 32.2 MJ (placebo) and 44.7 MJ (RSG). Fat cell size and expression of PPARgamma, adipocyte fatty acid-binding protein (aP2), adipsin, adiponectin and fasting-induced adipose factor (FIAF) were determined in subcutaneous abdominal fat biopsies. The total amount of fat stored and the amount of TAG per fat cell were not different between groups. For the entire group, fat cell size was decreased after overeating (P = 0.02). FIAF mRNA levels were decreased after overeating in the RSG group (P = 0.01), with a trend towards a decrease in the placebo group. Unexpectedly, RSG treatment did not influence the expression levels of PPARgamma and of the PPARgamma responsive genes aP2, adiponectin and adipsin. In addition, RSG resulted in a larger increase in plasma TAG during overeating than placebo treatment. These results suggest that in healthy, non-obese males the PPARgamma ligand RSG influences TAG metabolism, independent of its PPARgamma transcriptional activity in the subcutaneous adipose tissue.
Joosen
Annemiek M C P
AM
Department of Molecular Genetics, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands. amj@mrc-dunn.cam.ac.uk
Bakker
Arjen H F
AH
Kersten
Sander
S
Westerterp
Klaas R
KR
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000328:Adult; D000886:Anthropometry; D001786:Blood Glucose / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects; D002149:Energy Intake / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006963:Hyperphagia / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008024:Ligands; D008297:Male; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D000077154:Rosiglitazone; D050151:Subcutaneous Fat / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D045162:Thiazolidinediones / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects; D014280:Triglycerides / Q000378:metabolism*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D008024:Ligands; D047495:PPAR gamma; D012333:RNA, Messenger; D045162:Thiazolidinediones; D014280:Triglycerides; D000077154:Rosiglitazone