β1 Adrenergic receptor is key to cold-and diet-induced thermogenesis in mice

item.page.type
Artigo
Date
2012
item.page.ispartof
Journal of Endocrinology
item.page.citationsscopus
80
Authors
Ueta C.B.
Fernandes G.W.
Capelo L.P.
Fonseca T.L.
Maculan F.D.
Gouveia C.H.A.
Brum P.C.
Christoffolete M.A.
Aoki M.S.
Lancellotti C.L.
Kim B.
Bianco A.C.
Ribeiro M.O.
publication.page.advisor
Journal Title
Journal ISSN
Volume Title
publication.page.board
publication.page.program
Abstract
Brown adipose tissue (BAT) is predominantly regulated by the sympathetic nervous system (SNS) and the adrenergic receptor signaling pathway. Knowing that a mouse with triple β-receptor knockout (KO) is cold intolerant and obese, we evaluated the independent role played by the β1 isoform in energy homeostasis. First, the 30 min i.v. infusion of norepinephrine (NE) or the β1 selective agonist dobutamine (DB) resulted in similar interscapular BAT (iBAT) thermal response in WT mice. Secondly, mice with targeted disruption of the β1 gene (KO of β1 adrenergic receptor (β1KO)) developed hypothermia during cold exposure and exhibited decreased iBAT thermal response to NE or DB infusion. Thirdly, when placed on a high-fat diet (HFD; 40% fat) for 5 weeks, β1KO mice were more susceptible to obesity than WT controls and failed to develop diet-induced thermogenesis as assessed by BAT Ucp1 mRNA levels and oxygen consumption. Furthermore, β1KO mice exhibited fasting hyperglycemia and more intense glucose intolerance, hypercholesterolemia, and hypertriglyceridemia when placed on the HFD, developing marked non-alcoholic steatohepatitis. In conclusion, the β1 signaling pathway mediates most of the SNS stimulation of adaptive thermogenesis. © 2012 Society for Endocrinology.
Description
Keywords
item.page.scopussubject
Citation
item.page.doi