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High‐fat diet‐induced hepatic steatosis reduces glucagon receptor content in rat hepatocytes: potential interaction with acute exercise
Author(s) -
Charbonneau Alexandre,
Unson Cecilia G.,
Lavoie JeanMarc
Publication year - 2007
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2006.121954
Subject(s) - medicine , endocrinology , glucagon , glucagon receptor , insulin resistance , steatosis , fatty liver , chemistry , desensitization (medicine) , receptor , insulin , biology , disease
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‐α, suggesting a role of PKC‐α in GR desensitization. EX increased significantly PKC‐α protein content in both diets, suggesting a role of PKC‐α 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‐α.