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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adipose Tissue, Brown / innervation
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Adipose Tissue, Brown / metabolism*
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Animals
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Central Nervous System / metabolism*
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Glucagon / metabolism
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Glucagon-Like Peptide 1 / agonists
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Glucagon-Like Peptide 1 / metabolism*
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Glucagon-Like Peptide-1 Receptor
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Insulin Resistance
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Ion Channels / genetics
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Ion Channels / metabolism
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mitochondrial Proteins / genetics
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Mitochondrial Proteins / metabolism
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Neurons / metabolism
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Oxyntomodulin / metabolism
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
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Receptors, Glucagon / agonists
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Receptors, Glucagon / genetics
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Receptors, Glucagon / metabolism*
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Scapula
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Signal Transduction*
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Sympathetic Nervous System / metabolism
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Thermogenesis*
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Trans-Activators / genetics
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Trans-Activators / metabolism
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Transcription Factors
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Uncoupling Protein 1
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Up-Regulation
Substances
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Glp1r protein, mouse
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Glucagon-Like Peptide-1 Receptor
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Ion Channels
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Mitochondrial Proteins
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Nerve Tissue Proteins
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Oxyntomodulin
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
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Ppargc1a protein, mouse
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Receptors, Glucagon
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Trans-Activators
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Transcription Factors
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Ucp1 protein, mouse
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Uncoupling Protein 1
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Glucagon-Like Peptide 1
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Glucagon