High-fat diet-induced hepatic steatosis reduces glucagon receptor content in rat hepatocytes: potential interaction with acute exercise
High-fat diet-induced hepatic steatosis reduces glucagon receptor content in rat hepatocytes: potential interaction with acute exercise
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DOI：
10.1113/jphysiol.2006.121954
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发表时间：
2007-02-15
影响因子：
5.5
通讯作者：
Lavoie, Jean-Marc
中科院分区：
文献类型：
--
作者：
Charbonneau, Alexandre;Unson, Cecilia G.;Lavoie, Jean-Marc
研究表明，高脂(HF)饮食会导致高血糖、全身胰岛素抵抗和非酒精性脂肪性肝病(NAFLD)。最近，肝高血糖素抵抗被证明发生在喂食HF饮食的大鼠身上。更准确地说，饮食诱导的肥胖(DIO)减少了肝脏质膜上的胰高血糖素受体(GR)的数量，导致在高血糖素钳夹期间对胰高血糖素的反应减弱。本研究旨在验证以下假设：HF-DIO与肝脏GR的脱敏和破坏有关。我们还假设，在我们的DIO模型下，一次耐力运动将改变GR细胞的分布。雄性大鼠分别以标准饲料(SD)或HF饲料喂养两周。每组被细分为非运动组(休息)和急性运动组(EX)。HF饲料降低了肝脏GR总量(55%)和肝细胞质膜GR蛋白含量(20%)。伴随着这些变化的是，随着饲喂HF饲料，内体和溶酶体GR含量显著增加。GR质膜的减少和内体GR的增加与PKC-α的升高密切相关，提示PKC-α在GR脱敏中起作用。EX显著增加两种饲料中PKC-α的蛋白含量，提示PKC-α在EX诱导的GR脱敏中起作用。本研究结果提示，肝脏脂质渗入可能通过减少细胞和质膜GR的总含量来减少肝内高血糖素的作用。此外，在我们的HF饮食诱导的肝脏脂肪变性的活体模型中观察到的GR脱敏可能受PKC-α的调节。
Studies have revealed that high-fat (HF) diets promote hyperglycaemia, whole-body insulin resistance and non-alcoholic fatty liver disease (NAFLD). Recently, hepatic glucagon resistance has been shown to occur in rats fed a HF diet. More precisely, diet-induced obesity (DIO) reduces the number of hepatic plasma membrane glucagon receptors (GR), which results in a diminished response to glucagon during a hyperglucagonaemic clamp. The present study was undertaken to test the hypothesis that a HF-DIO is associated with a desensitization and destruction of the hepatic GR. We also hypothesized that a single bout of endurance exercise would modify the GR cellular distribution under our DIO model. Male rats were either fed a standard (SD) or a HF diet for two weeks. Each group was subdivided into a non-exercised (Rest) and an acute exercised (EX) group. The HF diet resulted in a reduction of total hepatic GR (55%) and hepatic plasma membrane GR protein content (20%). These changes were accompanied by a significant increase in endosomal and lysosomal GR content with the feeding of a HF diet. The reduction of GR plasma membrane as well as the increase in endosomal GR was strongly correlated with an increase of PKC-alpha, suggesting a role of PKC-alpha in GR desensitization. EX increased significantly PKC-alpha protein content in both diets, suggesting a role of PKC-alpha in EX-induced GR desensitization. The present results suggest that liver lipid infiltration plays a role in reducing glucagon action in the liver through a reduction in total cellular and plasma membrane GR content. Furthermore, the GR desensitization observed in our in vivo model of HF diet-induced hepatic steatosis and in EX individuals may be regulated by PKC-alpha.