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ß(1) Adrenergic receptor is key to cold- and diet-induced thermogenesis in mice.

Authors: Ueta, Cintia B  Fernandes, Gustavo W  Capelo, Luciane P  Fonseca, Tatiane L  Maculan, Flávia D'Angelo  Gouveia, Cecilia H A  Brum, Patrícia C  Christoffolete, Marcelo A  Aoki, Marcelo S  Lancellotti, Carmen L  Kim, Brian  Bianco, Antonio C  Ribeiro, Miriam O 
Citation: Ueta CB, etal., J Endocrinol. 2012 Sep;214(3):359-65. doi: 10.1530/JOE-12-0155. Epub 2012 Jun 22.
Pubmed: (View Article at PubMed) PMID:22728333
DOI: Full-text: DOI:10.1530/JOE-12-0155

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 ß-receptor knockout (KO) is cold intolerant and obese, we evaluated the independent role played by the ß(1) isoform in energy homeostasis. First, the 30 min i.v. infusion of norepinephrine (NE) or the ß(1) selective agonist dobutamine (DB) resulted in similar interscapular BAT (iBAT) thermal response in WT mice. Secondly, mice with targeted disruption of the ß(1) gene (KO of ß(1) adrenergic receptor (ß(1)KO)) 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, ß(1)KO 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, ß(1)KO 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 ß(1) signaling pathway mediates most of the SNS stimulation of adaptive thermogenesis.

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RGD Object Information
RGD ID: 13673867
Created: 2018-06-23
Species: All species
Last Modified: 2018-06-23
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.