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

First Author  Ueta CB Year  2012
Journal  J Endocrinol Volume  214
Issue  3 Pages  359-65
PubMed ID  22728333 Mgi Jnum  J:249901
Mgi Id  MGI:6101075 Doi  10.1530/JOE-12-0155
Citation  Ueta CB, et al. (2012) beta(1) Adrenergic receptor is key to cold- and diet-induced thermogenesis in mice. J Endocrinol 214(3):359-65
abstractText  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 beta-receptor knockout (KO) is cold intolerant and obese, we evaluated the independent role played by the beta(1) isoform in energy homeostasis. First, the 30 min i.v. infusion of norepinephrine (NE) or the beta(1) selective agonist dobutamine (DB) resulted in similar interscapular BAT (iBAT) thermal response in WT mice. Secondly, mice with targeted disruption of the beta(1) gene (KO of beta(1) adrenergic receptor (beta(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, beta(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, beta(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 beta(1) signaling pathway mediates most of the SNS stimulation of adaptive thermogenesis.
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