Journal article
Direct Control of Brown Adipose Tissue Thermogenesis by Central Nervous System Glucagon-Like Peptide-1 Receptor Signaling
Diabetes (New York, N.Y.), Vol.61(11), pp.2753-2762
11/2012
DOI: 10.2337/db11-1556
PMCID: PMC3478556
PMID: 22933116
Abstract
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.
Details
- Title: Subtitle
- Direct Control of Brown Adipose Tissue Thermogenesis by Central Nervous System Glucagon-Like Peptide-1 Receptor Signaling
- Creators
- Sarah H Lockie - Department of Internal Medicine, Metabolic Disease Institute, University of Cincinnati, Cincinnati, OhioKristy M Heppner - Department of Internal Medicine, Metabolic Disease Institute, University of Cincinnati, Cincinnati, OhioNilika Chaudhary - Department of Internal Medicine, Metabolic Disease Institute, University of Cincinnati, Cincinnati, OhioJoseph R Chabenne - Department of Chemistry, Indiana University, Bloomington, IndianaDonald A Morgan - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IowaChristelle Veyrat-Durebex - Department of Internal Medicine, Laboratory of Metabolism, Division of Endocrinology, Diabetology and Nutrition, University of Geneva, Geneva, SwitzerlandGayathri Ananthakrishnan - Department of Internal Medicine, Metabolic Disease Institute, University of Cincinnati, Cincinnati, OhioFrançoise Rohner-Jeanrenaud - Department of Internal Medicine, Laboratory of Metabolism, Division of Endocrinology, Diabetology and Nutrition, University of Geneva, Geneva, SwitzerlandDaniel J Drucker - Department of Medicine, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, CanadaRichard DiMarchi - Department of Chemistry, Indiana University, Bloomington, IndianaKamal Rahmouni - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IowaBrian J Oldfield - Department of Physiology, Monash University, Melbourne, AustraliaMatthias H Tschöp - Department of Internal Medicine, Metabolic Disease Institute, University of Cincinnati, Cincinnati, OhioDiego Perez-Tilve - Department of Internal Medicine, Metabolic Disease Institute, University of Cincinnati, Cincinnati, Ohio
- Resource Type
- Journal article
- Publication Details
- Diabetes (New York, N.Y.), Vol.61(11), pp.2753-2762
- Publisher
- American Diabetes Association
- DOI
- 10.2337/db11-1556
- PMID
- 22933116
- PMCID
- PMC3478556
- ISSN
- 0012-1797
- eISSN
- 1939-327X
- Language
- English
- Date published
- 11/2012
- Academic Unit
- Iowa Neuroscience Institute; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040327402771
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