Ljungberg Anna, Lindén Daniel, Améen Caroline, Bergström Göran, Oscarsson Jan
Wallenberg Laboratory for Cardiovascular Research, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden.
Growth Horm IGF Res. 2007 Apr;17(2):154-64. doi: 10.1016/j.ghir.2007.01.003. Epub 2007 Feb 20.
Growth hormone (GH) enhances lipolysis in adipose tissue, thereby increasing the flux of fatty acids to other tissues. Moreover, GH increases hepatic triglyceride synthesis and secretion in rats and decreases the action of peroxisome proliferator-activated receptor (PPAR)alpha. PPARalpha is activated by fatty acids and regulates hepatic lipid metabolism in rodents. The aim of this study was to investigate the importance of PPARalpha for the effects of GH on hepatic gene expression and lipoprotein metabolism.
Bovine GH was given as a continuous infusion (5mg/kg/day) for 7 days to PPARalpha-null and wild-type (wt) mice. Plasma and liver lipids and hepatic gene expression were measured. In separate experiments, hepatic triglyceride secretion was measured.
GH treatment decreased hepatic triglyceride content and increased hepatic triglyceride secretion rate and serum cholesterol levels. Furthermore, GH increased hepatic acylCoA:diacylglycerol acyltransferase (DGAT)2 mRNA levels, but decreased the hepatic mRNA expression of acyl-CoA oxidase, medium-chain acyl-CoA dehydrogenase and PPARgamma1. All these GH effects were independent of PPARalpha. However, the effect of GH on Cyp4a10, PPARgamma2, and DGAT1 was different between the genotypes. GH treatment decreased Cyp4a10 mRNA expression in wt mice, but increased the expression in PPARalpha-null mice. In contrast, GH decreased the expression of DGAT1 and PPARgamma2 in PPARalpha-null mice, but not in wt mice.
Most of the effects of GH on lipid and lipoprotein metabolism were independent of PPARalpha. However, GH had unique effects on Cyp4a10, DGAT1, and PPARgamma2 gene expression in PPARalpha-null mice showing cross-talk between GH and PPARalpha signalling in vivo.
生长激素（GH）可增强脂肪组织中的脂肪分解，从而增加脂肪酸向其他组织的流量。此外，GH可增加大鼠肝脏甘油三酯的合成与分泌，并降低过氧化物酶体增殖物激活受体（PPAR）α的活性。PPARα可被脂肪酸激活，并调节啮齿动物的肝脏脂质代谢。本研究旨在探讨PPARα对GH影响肝脏基因表达及脂蛋白代谢的重要性。
对PPARα基因敲除小鼠和野生型（wt）小鼠持续输注牛GH（5mg/kg/天）7天。检测血浆和肝脏脂质以及肝脏基因表达。在单独的实验中，检测肝脏甘油三酯分泌情况。
GH治疗可降低肝脏甘油三酯含量，增加肝脏甘油三酯分泌率和血清胆固醇水平。此外，GH可增加肝脏酰基辅酶A：二酰甘油酰基转移酶（DGAT）2的mRNA水平，但可降低酰基辅酶A氧化酶、中链酰基辅酶A脱氢酶和PPARγ1的肝脏mRNA表达。所有这些GH的作用均与PPARα无关。然而，GH对Cyp4a10、PPARγ2和DGAT1的作用在不同基因型之间存在差异。GH治疗可降低wt小鼠中Cyp4a10的mRNA表达，但可增加PPARα基因敲除小鼠中的表达。相反，GH可降低PPARα基因敲除小鼠中DGAT1和PPARγ2的表达，但对wt小鼠无此作用。
GH对脂质和脂蛋白代谢的大多数作用与PPARα无关。然而，GH对PPARα基因敲除小鼠中的Cyp4a10、DGAT1和PPARγ2基因表达具有独特作用，表明体内GH与PPARα信号通路之间存在相互作用。
