Alterations in hepatic glucagon receptor density and in Gs and Gi 2 protein content with diet-induced hepatic steatosis: effects of acute exercise

Charbonneau, Alexandre, Alexandre Melancon, Carole Lavoie, and Jean-Marc Lavoie. Alterations in hepatic glucagon receptor density and in Gs and Gi 2 protein content with diet-induced hepatic steatosis: effects of acute exercise. Am J Physiol Endocrinol Metab 289: E8–E14, 2005. First published February 1, 2005; doi:10.1152/ajpendo.00570.2004.—The present study was undertaken to test the hypothesis that a high-fat dietinduced liver lipid infiltration is associated with a reduction of hepatic glucagon receptor density (Bmax) and affinity (Kd), and with a decrease in stimulatory G protein (Gs ) content while enhancing inhibitory G protein (Gi 2) expression. We also hypothesized that, under this dietary condition, a single bout of endurance exercise would restore hepatic glucagon receptor parameters and G protein expression to standard levels. Female Sprague-Dawley rats were fed either a standard (SD) or a high-fat diet (HF; 40% kcal) for 2 wk (n 20 rats/group). Each dietary group was thereafter subdivided into a nonexercised (Rest) and an acute-exercised group (Ac-Ex). The acute exercise consisted of a single bout of endurance exercise on a treadmill (30 min, 26 m/min, and 0% slope) immediately before being killed. The HF compared with the SD diet was associated with significantly (P 0.05) higher values in hepatic triglyceride concentrations (123%), fat pad weight, and plasma free fatty acid (FFA) concentrations. The HF diet also resulted in significantly (P 0.05) lower hepatic glucagon receptor density (45%) and Gs protein content (75%), as well as higher (P 0.05) Gi 2 protein content (27%), with no significant effects on glucagon receptor affinity. Comparisons of all individual liver triglyceride and Bmax values revealed that liver triglycerides were highly (P 0.003) predictive of the decreased glucagon receptor density (R 0.512). Although the 30-min exercise bout resulted in some typical exercise effects (P 0.05), such as an increase in FFA (SD diet), a decrease in insulin levels, and an increase in plasma glucagon concentrations (SD diet), it did not change any of the responses related to liver glucagon receptors and G proteins, with the exception of a significant (P 0.05) decrease in Gi 2 protein content under the HF diet. The present results indicate that the feeding of an HF diet is associated with a reduction in plasma membrane hepatic glucagon receptor density and Gs protein content, which is not attenuated by a 30-min exercise bout. It is suggested that liver lipid infiltration plays a role in reducing glucagon action in the liver through a reduction in glucagon receptor density and glucagon-mediated signal transduction.