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

Corresponding author: Diego Perez-Tilve, .
Diabetes (Impact Factor: 8.1). 08/2012; 61(11):2753-62. DOI: 10.2337/db11-1556
Source: PubMed


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.

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    • "The AP and SFO, which form part of the brains' circumventricular organs, also contained large numbers of GLP-1R expressing cells. Moderate numbers of GLP-1R expressing cells were observed in the ventrolateral medulla, which like the PVN harbours presympathetic neurons, and thus both regions might contribute to the effects of GLP-1 on cardiovascular control as well as thermogenesis [8] [9] [33]. Of particular interest were brain areas such as the VTA and NAc, which have recently received attention for their ability to reduce food intake and reward behaviour following GLP-1R activation [10] [34] [35]. "
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    • "In addition to causing changes in feeding , central GLP - 1R activa - tion may regulate body weight by increasing brown adipose tissue ( BAT ) thermogenesis ( reviewed in Lockie et al . , 2013 ) . Chronic ICV administration of oxyntomodulin , a GLP - 1R agonist , in mice decreased body weight despite having no significant effects on food intake ( Lockie et al . , 2012 ) . Interestingly , BAT temperature was increased in these animals , which may have contributed to the weight loss . The effect of oxyntomodulin on body weight and BAT temperature is not evident in mice that lack the GLP - 1R highlighting a GLP - 1R dependent action . To determine the site of GLP - 1R mediated action on BAT thermogenesi"
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