Lapsys N M, Kriketos A D, Lim-Fraser M, Poynten A M, Lowy A, Furler S M, Chisholm D J, Cooney G J
Metabolism and Diabetes Research Group, The Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
J Clin Endocrinol Metab. 2000 Nov;85(11):4293-7. doi: 10.1210/jcem.85.11.6973.
Peroxisome proliferator-activated receptor gamma (PPAR-gamma) activation in adipose tissue is known to regulate genes involved in adipocyte differentiation and lipid metabolism. However, the role of PPAR-gamma in muscle remains unclear. To examine the potential regulation of genes by PPAR-gamma in human skeletal muscle, we used semiquantitative RT-PCR to determine the expression of PPAR-gamma, lipoprotein lipase (LPL), muscle carnitine palmitoyl transferase-1 (mCPT1), fatty acid-binding protein (FABP), carnitine acylcarnitine transferase (CACT), and glucose transporter-4 (GLUT4) in freeze-dried muscle samples from 14 male subjects. These samples were dissected free of adipose and other tissue contamination, as confirmed by minimal or absent adipsin expression. Between individuals, the messenger ribonucleic acid concentration of PPAR-gamma varied up to 3-fold, whereas LPL varied up to 6.5-fold, mCPT1 13-fold, FABP 4-fold, CACT 4-fold, and GLUT4 up to 3-fold. The expression of LPL (r2 = 0.54; P = 0.003), mCPT1 (r2 = 0.42; P = 0.012), and FABP (r2 = 0.324; P = 0.034) all correlated significantly with PPAR-gamma expression in the same samples. No significant correlation was observed between the expression of CACT and PPAR-gamma or between GLUT4 and PPAR-gamma. These findings demonstrate a relationship between PPAR-gamma expression and the expression of other genes of lipid metabolism in muscle and support the hypothesis that PPAR-gamma activators such as the antidiabetic thiazolidinediones may regulate fatty acid metabolism in skeletal muscle as well as in adipose tissue.
已知脂肪组织中过氧化物酶体增殖物激活受体γ（PPAR-γ）的激活可调节参与脂肪细胞分化和脂质代谢的基因。然而，PPAR-γ在肌肉中的作用仍不清楚。为了研究PPAR-γ对人类骨骼肌中基因的潜在调控作用，我们使用半定量逆转录聚合酶链反应（RT-PCR）来测定14名男性受试者冻干肌肉样本中PPAR-γ、脂蛋白脂肪酶（LPL）、肌肉肉碱棕榈酰转移酶-1（mCPT1）、脂肪酸结合蛋白（FABP）、肉碱酰基肉碱转移酶（CACT）和葡萄糖转运蛋白4（GLUT4）的表达。经检测，这些样本中脂肪酶表达极少或无表达，确认已去除脂肪和其他组织污染。个体之间，PPAR-γ的信使核糖核酸浓度变化高达3倍，而LPL变化高达6.5倍，mCPT1变化13倍，FABP变化4倍，CACT变化4倍，GLUT4变化高达3倍。在相同样本中，LPL（r2 = 0.54；P = 0.003）、mCPT1（r2 = 0.42；P = 0.012）和FABP（r2 = 0.324；P = 0.034）的表达均与PPAR-γ表达显著相关。未观察到CACT表达与PPAR-γ之间或GLUT4与PPAR-γ之间存在显著相关性。这些发现证明了PPAR-γ表达与肌肉中其他脂质代谢基因表达之间的关系，并支持以下假说：抗糖尿病噻唑烷二酮类等PPAR-γ激活剂可能在骨骼肌以及脂肪组织中调节脂肪酸代谢。
