Alterations in hepatic glucagon receptor density and in Gsalpha and Gialpha2 protein content with diet-induced hepatic steatosis: effects of acute exercise.
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)alpha) content while enhancing inhibitory G protein (G(i)alpha(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 G(s)alpha protein content (75%), as well as higher (P < 0.05) G(i)alpha(2) 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(i)alpha(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 G(s)alpha 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.
Charbonneau
Alexandre
A
Département de Kinésiologie, Université de Montréal, C.P. 6128, Succ. Centre-Ville, Montreal, QC, Canada, H3C 3J7.
Melancon
Alexandre
A
Lavoie
Carole
C
Lavoie
Jean-Marc
JM
D000222:Adaptation, Physiological; D000818:Animals; D001835:Body Weight; D004041:Dietary Fats / Q000378:metabolism*; D005234:Fatty Liver / Q000378:metabolism*; D005260:Female; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism*; D008099:Liver / Q000503:physiopathology*; D009929:Organ Size; D010807:Physical Endurance; D051381:Rats; D017207:Rats, Sprague-Dawley; D018027:Receptors, Glucagon / Q000378:metabolism*
D004041:Dietary Fats; D018027:Receptors, Glucagon; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D019205:GTP-Binding Protein alpha Subunits, Gs