TY - JOUR
T1 - β1 Adrenergic receptor is key to cold-and diet-induced thermogenesis in mice
AU - Ueta, Cintia B.
AU - Fernandes, Gustavo W.
AU - Capelo, Luciane P.
AU - Fonseca, Tatiane L.
AU - Maculan, Flávia D.Angelo
AU - Gouveia, Cecilia H.A.
AU - Brum, Patrícia C.
AU - Christoffolete, Marcelo A.
AU - Aoki, Marcelo S.
AU - Lancellotti, Carmen L.
AU - Kim, Brian
AU - Bianco, Antonio C.
AU - Ribeiro, Miriam O.
PY - 2012/9
Y1 - 2012/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84866276013&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84866276013&partnerID=8YFLogxK
U2 - 10.1530/JOE-12-0155
DO - 10.1530/JOE-12-0155
M3 - Article
C2 - 22728333
AN - SCOPUS:84866276013
SN - 0022-0795
VL - 214
SP - 359
EP - 365
JO - Journal of Endocrinology
JF - Journal of Endocrinology
IS - 3
ER -