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 journalArticle

123 Citations (Scopus)

Abstract

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
Volume8
Issue number5
DOIs
StatePublished - Nov 5 2008

Fingerprint

Glucagon Receptors
Fasting
Fatty Acids
Glucagon
Lipid Metabolism
Hepatocytes
Liver
Triglycerides
Peroxisome Proliferator-Activated Receptors
Glucose
Messenger RNA

Keywords

  • HUMDISEASE

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

Cite this

Longuet, C., Sinclair, E. M., Maida, A., Baggio, L. L., Maziarz, M., Charron, M. J., & Drucker, D. J. (2008). The Glucagon Receptor Is Required for the Adaptive Metabolic Response to Fasting. Cell Metabolism, 8(5), 359-371. https://doi.org/10.1016/j.cmet.2008.09.008

The Glucagon Receptor Is Required for the Adaptive Metabolic Response to Fasting. / Longuet, Christine; Sinclair, Elaine M.; Maida, Adriano; Baggio, Laurie L.; Maziarz, Marlena; Charron, Maureen J.; Drucker, Daniel J.

In: Cell Metabolism, Vol. 8, No. 5, 05.11.2008, p. 359-371.

Research output: Contribution to journalArticle

Longuet, C, Sinclair, EM, Maida, A, Baggio, LL, Maziarz, M, Charron, MJ & Drucker, DJ 2008, 'The Glucagon Receptor Is Required for the Adaptive Metabolic Response to Fasting', Cell Metabolism, vol. 8, no. 5, pp. 359-371. https://doi.org/10.1016/j.cmet.2008.09.008
Longuet, Christine ; Sinclair, Elaine M. ; Maida, Adriano ; Baggio, Laurie L. ; Maziarz, Marlena ; Charron, Maureen J. ; Drucker, Daniel J. / The Glucagon Receptor Is Required for the Adaptive Metabolic Response to Fasting. In: Cell Metabolism. 2008 ; Vol. 8, No. 5. pp. 359-371.
@article{fd14d7c60d0d4eddbb5da522a99f66dc,
title = "The Glucagon Receptor Is Required for the Adaptive Metabolic Response to Fasting",
abstract = "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.",
keywords = "HUMDISEASE",
author = "Christine Longuet and Sinclair, {Elaine M.} and Adriano Maida and Baggio, {Laurie L.} and Marlena Maziarz and Charron, {Maureen J.} and Drucker, {Daniel J.}",
year = "2008",
month = "11",
day = "5",
doi = "10.1016/j.cmet.2008.09.008",
language = "English (US)",
volume = "8",
pages = "359--371",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "5",

}

TY - JOUR

T1 - The Glucagon Receptor Is Required for the Adaptive Metabolic Response to Fasting

AU - Longuet, Christine

AU - Sinclair, Elaine M.

AU - Maida, Adriano

AU - Baggio, Laurie L.

AU - Maziarz, Marlena

AU - Charron, Maureen J.

AU - Drucker, Daniel J.

PY - 2008/11/5

Y1 - 2008/11/5

N2 - 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.

AB - 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.

KW - HUMDISEASE

UR - http://www.scopus.com/inward/record.url?scp=54849431792&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=54849431792&partnerID=8YFLogxK

U2 - 10.1016/j.cmet.2008.09.008

DO - 10.1016/j.cmet.2008.09.008

M3 - Article

VL - 8

SP - 359

EP - 371

JO - Cell Metabolism

JF - Cell Metabolism

SN - 1550-4131

IS - 5

ER -