beta(1) Adrenergic receptor is key to cold- and diet-induced thermogenesis in mice
Contribuinte(s) |
UNIVERSIDADE DE SÃO PAULO |
---|---|
Data(s) |
05/11/2013
05/11/2013
2012
|
Resumo |
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 1KO)) 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 1KO 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 1KO 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. Journal of Endocrinology (2012) 214, 359-365 Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) MackPesquisa, Brazil MackPesquisa, Brazil |
Identificador |
Journal of Endocrinology, Bristol, v. 214, n. 3, supl. 4, Part 1-2, pp. 359-365, sep, 2012 0022-0795 http://www.producao.usp.br/handle/BDPI/41317 10.1530/JOE-12-0155 |
Idioma(s) |
eng |
Publicador |
Bioscientifica Ltd Bristol |
Relação |
Journal of Endocrinology |
Direitos |
restrictedAccess Copyright BIOSCIENTIFICA LTD |
Palavras-Chave | #Brown adipose-tissue #Adaptive thermogenesis #Thyroid-hormone #Targeted disruption #Glucose-transport #Energy-Balance #Obesity #Adipocytes #Beta(3)-Adrenoceptors #Dobutamine #Endocrinology & metabolism |
Tipo |
article original article publishedVersion |