The PPAR-γ agonist rosiglitazone enhances rat brown adipose tissue lipogenesis from glucose without altering glucose uptake.

Autor: Festuccia, William T., Blanchard, Pierre-Gilles, Turcotte, Véronique, Laplante, Mathieu, Sariahmetoglu, Meltem, Brindley, David N., Richard, Denis, Deshaies, Yves
Předmět:
Zdroj: American Journal of Physiology: Regulatory, Integrative & Comparative Physiology; May2009, Vol. 296, pR1327-R1335, 9p, 1 Diagram, 1 Chart, 6 Graphs
Abstrakt: We investigated the mechanisms whereby peroxisome proliferator-activated receptor-γ (PPARγ) agonism affects glucose and lipid metabolism in brown adipose tissue (BAT) by studying the impact of PPAR-γ 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 mgkg-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 glyceroiphosphate 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 UDPlinked 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 PPARy activation may constitute an important mechanism by which lipid substrates are stored in preparation for an eventual thermogenic activation. [ABSTRACT FROM AUTHOR]
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