The Glucagon Receptor Is Required for the Adaptive Metabolic Response to Fasting
The Glucagon Receptor Is Required for the Adaptive Metabolic Response to Fasting
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DOI：
10.1016/j.cmet.2008.09.008
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发表时间：
2008-11-05
期刊：
影响因子：
29
通讯作者：
Drucker, Daniel J.
中科院分区：
文献类型：
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作者：
Longuet, Christine;Sinclair, Elaine M.;Drucker, Daniel J.
胰高血糖素受体（Gcgr）信号在空腹状态下维持肝脏葡萄糖的产生;然而，Gcgr对脂质代谢的重要性尚不清楚。我们在这里表明，禁食Gcgr-/-小鼠表现出显着增加肝脏甘油三酯分泌和禁食增加脂肪酸氧化（FAO）在野生型（WT），但不是在Gcgr-/-小鼠。此外，禁食上调了Gcgr+/+小鼠的FAO相关肝脏mRNA转录本的表达，但在Gcgr-/-小鼠中没有。外源性胰高血糖素给药可降低WT小鼠的血浆甘油三酯，抑制TG合成和分泌，并刺激Gcgr+/+肝细胞中的FA β氧化。胰高血糖素对TG合成和FAO的作用在PPAR α-/-肝细胞中被消除。这些发现表明，Gcgr受体是需要在禁食的适应性代谢反应的脂质代谢的控制。
Glucagon receptor (Gcgr) signaling maintains hepatic glucose production during the fasting state; however, the importance of the Gcgr for lipid metabolism is unclear. We show here that fasted Gcgr-/- mice exhibit a significant increase in hepatic triglyceride secretion and fasting increases fatty acid oxidation (FAO) in wild-type (WT) but not in Gcgr-/- mice. Moreover fasting upregulated the expression of FAO-related hepatic mRNA transcripts in Gcgr+/+ but not in Gcgr-/- mice. Exogenous glucagon administration reduced plasma triglycerides in WT mice, inhibited TG synthesis and secretion, and stimulated FA beta oxidation in Gcgr+/+ hepatocytes. The actions of glucagon on TG synthesis and FAO were abolished in PPAR alpha-/- hepatocytes. These findings demonstrate that the Gcgr receptor is required for control of lipid metabolism during the adaptive metabolic response to fasting.