The PPARgamma agonist rosiglitazone enhances rat brown adipose tissue lipogenesis from glucose without altering glucose uptake.
We investigated the mechanisms whereby peroxisome proliferator-activated receptor-gamma (PPARgamma) agonism affects glucose and lipid metabolism in brown adipose tissue (BAT) by studying the impact of PPARgamma activation on BAT glucose uptake and metabolism, lipogenesis, and mRNA levels plus activities of enzymes involved in triacylglycerol (TAG) synthesis. Interscapular BAT of rats treated or not with rosiglitazone (15 mg*kg(-1).day(-1), 7 days) was evaluated in vivo for glucose uptake and lipogenesis and in vitro for glucose metabolism, gene expression, and activities of glycerolphosphate acyltransferase (GPAT), phosphatidate phosphatase-1 (PAP or lipin-1), and diacylglycerol acyltransferase (DGAT). Rosiglitazone increased BAT mass without affecting whole tissue glucose uptake. BAT glycogen content (-80%), its synthesis from glucose (-50%), and mRNA levels of UDP-glucose pyrophosphorylase (-40%), which generates UDP-linked glucose for glycogen synthesis, were all reduced by rosiglitazone. In contrast, BAT TAG-glycerol synthesis in vivo and glucose incorporation into TAG-glycerol in vitro were stimulated by the agonist along with the activities and mRNA levels of glycerol 3-phosphate-generating phosphoenolpyruvate carboxykinase and glycerokinase. Furthermore, rosiglitazone markedly increased the activities of GPAT and DGAT but not those of lipin-1-mediated PAP-1, enzymes involved in the sequential acylation of glycerol 3-phosphate and TAG synthesis. Because an adequate supply of fatty acids is essential for BAT nonshivering thermogenesis, the enhanced ability of BAT to synthesize TAG under PPARgamma activation may constitute an important mechanism by which lipid substrates are stored in preparation for an eventual thermogenic activation.
Festuccia
William T
WT
Laval Hospital Research Centre and Department of Anatomy and Physiology, Faculty of Medicine, Laval University, Quebec, QC, Canada G1V 4G5.
Blanchard
Pierre-Gilles
PG
Turcotte
Véronique
V
Laplante
Mathieu
M
Sariahmetoglu
Meltem
M
Brindley
David N
DN
Richard
Denis
D
Deshaies
Yves
Y
D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D051048:Diacylglycerol O-Acyltransferase / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D007773:Lactates / Q000378:metabolism; D050155:Lipogenesis / Q000187:drug effects*; D008297:Male; D023421:Models, Animal; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D000073718:Pancreatitis-Associated Proteins; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D014280:Triglycerides / Q000378:metabolism
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D007773:Lactates; D047495:PPAR gamma; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human; D012333:RNA, Messenger; D045162:Thiazolidinediones; D014280:Triglycerides; D000077154:Rosiglitazone; D006003:Glycogen; C494883:Dgat1 protein, rat; D051048:Diacylglycerol O-Acyltransferase; D005947:Glucose