title: Contribution of brown adipose tissue activity to the control of energy balance by GLP-1 receptor signalling in mice.
abstract: OBJECTIVE
  We assessed the contribution of glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) signalling to thermogenesis induced by high-fat diet (HFD) consumption. Furthermore, we determined whether brown adipose tissue (BAT) activity contributes to weight loss induced by chronic subcutaneous treatment with the GLP-1R agonist, liraglutide, in a model of diet-induced obesity.
  
  
  METHODS
  Metabolic phenotyping was performed using indirect calorimetry in wild-type (WT) and Glp1r-knockout (KO) mice during chow and HFD feeding at room temperature and at thermoneutrality. In a separate study, we investigated the contribution of BAT thermogenic capacity to the weight lowering effect induced by GLP-1 mimetics by administering liraglutide (10 or 30 nmol kg(-1) day(-1) s.c.) to diet-induced obese (DIO) mice for 6 or 4 weeks, respectively. In both studies, animals were subjected to a noradrenaline (norepinephrine)-stimulated oxygen consumption [Formula: see text] test.
  
  
  RESULTS
  At thermoneutrality, HFD-fed Glp1r-KO mice had similar energy expenditure (EE) compared with HFD-fed WT controls. However, HFD-fed Glp1r-KO mice exhibited relatively less EE when housed at a cooler standard room temperature, and had relatively lower [Formula: see text] in response to a noradrenaline challenge, which is consistent with impaired BAT thermogenic capacity. In contrast to the loss of function model, chronic peripheral liraglutide treatment did not increase BAT activity as determined by noradrenaline-stimulated [Formula: see text] and BAT gene expression.
  
  
  CONCLUSIONS
  These data suggest that although endogenous GLP-1R signalling contributes to increased BAT thermogenesis, this mechanism does not play a significant role in the food intake-independent body weight lowering effect of the GLP-1 mimetic liraglutide in DIO mice.
authors.affiliation: Metabolic Diseases Institute, Department of Medicine/Internal Medicine, University of Cincinnati, 2180 E. Galbraith Road, A-125, Cincinnati, OH, 45220, USA.
authors.forename: Kristy M
authors.initials: KM
authors.lastname: Heppner
authors.forename: Sarah
authors.initials: S
authors.lastname: Marks
authors.forename: Jenna
authors.initials: J
authors.lastname: Holland
authors.forename: Nickki
authors.initials: N
authors.lastname: Ottaway
authors.forename: David
authors.initials: D
authors.lastname: Smiley
authors.forename: Richard
authors.initials: R
authors.lastname: Dimarchi
authors.forename: Diego
authors.initials: D
authors.lastname: Perez-Tilve
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D001823:Body Composition; D002153:Calorimetry, Indirect; D004032:Diet; D059305:Diet, High-Fat; D004435:Eating; D004734:Energy Metabolism / Q000502:physiology; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism*; D000069450:Liraglutide / Q000737:chemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D009638:Norepinephrine / Q000737:chemistry; D010101:Oxygen Consumption; D010641:Phenotype; D015398:Signal Transduction; D013696:Temperature; D022722:Thermogenesis
chemical_list: C000593834:Glp1r protein, mouse; D000067757:Glucagon-Like Peptide-1 Receptor; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D009638:Norepinephrine