title: UCP1 ablation induces obesity and abolishes diet-induced thermogenesis in mice exempt from thermal stress by living at thermoneutrality.
abstract: As original studies of UCP1-ablated mice failed to demonstrate an obesogenic effect, alternative mechanisms for adaptive adrenergic thermogenesis have been sought. However, we demonstrate here that in C57Bl6 mice exempt from thermal stress (i.e., kept at thermoneutrality), UCP1 ablation in itself induced obesity, even in mice fed control diet, and vastly augmented diet-induced obesity (high-fat diet); i.e., the mice exhibited increased metabolic efficiency. In wild-type mice, high-fat diet increased norepinephrine-induced thermogenesis; i.e., diet-induced thermogenesis was observed, but no such effect was observed in UCP1-ablated mice, demonstrating that diet-induced thermogenesis fully emanates from UCP1 activity. We conclude that ambient temperature is qualitatively determinative for the outcome of metabolic studies, that no other protein and no other mechanism can substitute for UCP1 in mediating diet-induced adrenergic thermogenesis, and that UCP1 activity can be determinative for obesity development in mice and possibly in humans.
authors.affiliation: The Wenner-Gren Institute, The Arrhenius Laboratories F3, Stockholm University, Stockholm, Sweden.
authors.forename: Helena M
authors.initials: HM
authors.lastname: Feldmann
authors.forename: Valeria
authors.initials: V
authors.lastname: Golozoubova
authors.forename: Barbara
authors.initials: B
authors.lastname: Cannon
authors.forename: Jan
authors.initials: J
authors.lastname: Nedergaard
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism; D000818:Animals; D004435:Eating; D004734:Energy Metabolism; D006801:Humans; D007473:Ion Channels / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D009765:Obesity / Q000209:etiology*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D013312:Stress, Physiological; D013696:Temperature; D022722:Thermogenesis; D000071256:Uncoupling Protein 1
chemical_list: D007473:Ion Channels; D024101:Mitochondrial Proteins; D011943:Receptors, Adrenergic, beta; C000604371:UCP1 protein, human; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D009638:Norepinephrine