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Alterations in hepatic glucagon receptor density and in G_s and G_i2 protein content with diet-induced hepatic steatosis: effects of acute exercise

¹Département de Kinésiologie, Université de Montréal, Montreal; and ²Département des Sciences de l'Activité Physique, Université du Québec à Trois-Rivières, Trois-Rivières, Quebec, Canada

Submitted 3 December 2004 ; accepted in final form 28 January 2005

The present study was undertaken to test the hypothesis that a high-fat diet-induced liver lipid infiltration is associated with a reduction of hepatic glucagon receptor density (B_max) and affinity (K_d), and with a decrease in stimulatory G protein (G_s) content while enhancing inhibitory G protein (G_i2) 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 G_s protein content (75%), as well as higher (P < 0.05) G_i2 protein content (27%), with no significant effects on glucagon receptor affinity. Comparisons of all individual liver triglyceride and B_max 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 G_i2 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 G_s 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.

liver lipid infiltration; glucagon receptor affinity; fat deposits; high-fat diet; liver

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