The Glucagon Receptor Is Required for the Adaptive Metabolic Response to Fasting

Christine Longuet, Elaine M. Sinclair, Adriano Maida, Laurie L. Baggio, Marlena Maziarz, Maureen J. Charron, Daniel J. Drucker

Research output: Contribution to journalArticlepeer-review

184 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)359-371
Number of pages13
JournalCell metabolism
Issue number5
StatePublished - Nov 5 2008



ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology


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