Direct Control of Brown Adipose Tissue Thermogenesis by Central Nervous System Glucagon-Like Peptide-1 Receptor Signaling

  1. Diego Perez-Tilve1
  1. 1Department of Internal Medicine, Metabolic Disease Institute, University of Cincinnati, Cincinnati, Ohio
  2. 2Department of Physiology, Monash University, Melbourne, Australia
  3. 3Department of Chemistry, Indiana University, Bloomington, Indiana
  4. 4Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa
  5. 5Department of Internal Medicine, Laboratory of Metabolism, Division of Endocrinology, Diabetology and Nutrition, University of Geneva, Geneva, Switzerland
  6. 6Department of Medicine, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
  1. Corresponding author: Diego Perez-Tilve, pereztdo{at}


We studied interscapular brown adipose tissue (iBAT) activity in wild-type (WT) and glucagon-like peptide 1 receptor (GLP-1R)–deficient mice after the administration of the proglucagon-derived peptides (PGDPs) glucagon-like peptide (GLP-1), glucagon (GCG), and oxyntomodulin (OXM) directly into the brain. Intracerebroventricular injection of PGDPs reduces body weight and increases iBAT thermogenesis. This was independent of changes in feeding and insulin responsiveness but correlated with increased activity of sympathetic fibers innervating brown adipose tissue (BAT). Despite being a GCG receptor agonist, OXM requires GLP-1R activation to induce iBAT thermogenesis. The increase in thermogenesis in WT mice correlates with increased expression of genes upregulated by adrenergic signaling and required for iBAT thermogenesis, including PGC1a and UCP-1. In spite of the increase in iBAT thermogenesis induced by GLP-1R activation in WT mice, Glp1r−/− mice exhibit a normal response to cold exposure, demonstrating that endogenous GLP-1R signaling is not essential for appropriate thermogenic response after cold exposure. Our data suggest that the increase in BAT thermogenesis may be an additional mechanism whereby pharmacological GLP-1R activation controls energy balance.

  • Received November 6, 2011.
  • Accepted May 30, 2012.

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  1. Diabetes vol. 61 no. 11 2753-2762
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