[PDF][PDF] The glucagon receptor is required for the adaptive metabolic response to fasting

C Longuet, EM Sinclair, A Maida, LL Baggio, M Maziarz… - Cell metabolism, 2008 - cell.com
C Longuet, EM Sinclair, A Maida, LL Baggio, M Maziarz, MJ Charron, DJ Drucker
Cell metabolism, 2008cell.com
Glucagon receptor (Gcgr) signaling maintains hepatic glucose production during the fasting
state; however, the importance of the Gcgr for lipid metabolism is unclear. We show here that
fasted Gcgr−/− mice exhibit a significant increase in hepatic triglyceride secretion and fasting
increases fatty acid oxidation (FAO) in wild-type (WT) but not in Gcgr−/− mice. Moreover
fasting upregulated the expression of FAO-related hepatic mRNA transcripts in Gcgr+/+ but
not in Gcgr−/− mice. Exogenous glucagon administration reduced plasma triglycerides in …
Summary
Glucagon receptor (Gcgr) signaling maintains hepatic glucose production during the fasting state; however, the importance of the Gcgr for lipid metabolism is unclear. We show here that fasted Gcgr−/− mice exhibit a significant increase in hepatic triglyceride secretion and fasting increases fatty acid oxidation (FAO) in wild-type (WT) but not in Gcgr−/− mice. Moreover fasting upregulated the expression of FAO-related hepatic mRNA transcripts in Gcgr+/+ but not in Gcgr−/− mice. Exogenous glucagon administration reduced plasma triglycerides in WT mice, inhibited TG synthesis and secretion, and stimulated FA beta oxidation in Gcgr+/+ hepatocytes. The actions of glucagon on TG synthesis and FAO were abolished in PPARα−/− hepatocytes. These findings demonstrate that the Gcgr receptor is required for control of lipid metabolism during the adaptive metabolic response to fasting.
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