TY - JOUR
T1 - Disruption of beta3 adrenergic receptor increases susceptibility to DIO in mouse
AU - Preite, Nailliw Z.
AU - Do Nascimento, Bruna P.P.
AU - Muller, Cynthia R.
AU - Américo, Anna Laura V.
AU - Higa, Talita S.
AU - Evangelista, Fabiana S.
AU - Lancellotti, Carmen L.
AU - Henriques, Felipe dos Santos
AU - Batista, Miguel Luiz
AU - Bianco, Antonio C.
AU - Ribeiro, Miriam O.
N1 - Publisher Copyright:
© 2016 Society for Endocrinology.
PY - 2016
Y1 - 2016
N2 - The brown adipose tissue (BAT) mediates adaptive changes in metabolic rate by responding to the sympathetic nervous system through β-adrenergic receptors (AR). Here, we wished to define the role played by the ARβ3 isoform in this process. This study focused on the ARβ3 knockout mice (ARβ3KO), including responsiveness to cold exposure, diet-induced obesity, intolerance to glucose, dyslipidaemia and lipolysis in white adipose tissue (WAT). ARβ3KO mice defend core temperature during cold exposure (4°C for 5 h), with faster BAT thermal response to norepinephrine (NE) infusion when compared with wild-type (WT) mice. Despite normal BAT thermogenesis, ARβ3KO mice kept on a high-fat diet (HFD; 40% fat) for 8 weeks exhibited greater susceptibility to diet-induced obesity, markedly increased epididymal adipocyte area with clear signs of inflammation. The HFD-induced glucose intolerance was similar in both groups but serum hypertriglyceridemia and hypercholesterolemia were less intense in ARβ3KO animals when compared with WT controls. Isoproterenol-induced lipolysis in isolated white adipocytes as assessed by glycerol release was significantly impaired in ARβ3KO animals despite normal expression of key proteins involved in lipid metabolism. In conclusion, ARβ3 inactivation does not affect BAT thermogenesis but increases susceptibility to dietinduced obesity by dampening WAT lipolytic response to adrenergic stimulation.
AB - The brown adipose tissue (BAT) mediates adaptive changes in metabolic rate by responding to the sympathetic nervous system through β-adrenergic receptors (AR). Here, we wished to define the role played by the ARβ3 isoform in this process. This study focused on the ARβ3 knockout mice (ARβ3KO), including responsiveness to cold exposure, diet-induced obesity, intolerance to glucose, dyslipidaemia and lipolysis in white adipose tissue (WAT). ARβ3KO mice defend core temperature during cold exposure (4°C for 5 h), with faster BAT thermal response to norepinephrine (NE) infusion when compared with wild-type (WT) mice. Despite normal BAT thermogenesis, ARβ3KO mice kept on a high-fat diet (HFD; 40% fat) for 8 weeks exhibited greater susceptibility to diet-induced obesity, markedly increased epididymal adipocyte area with clear signs of inflammation. The HFD-induced glucose intolerance was similar in both groups but serum hypertriglyceridemia and hypercholesterolemia were less intense in ARβ3KO animals when compared with WT controls. Isoproterenol-induced lipolysis in isolated white adipocytes as assessed by glycerol release was significantly impaired in ARβ3KO animals despite normal expression of key proteins involved in lipid metabolism. In conclusion, ARβ3 inactivation does not affect BAT thermogenesis but increases susceptibility to dietinduced obesity by dampening WAT lipolytic response to adrenergic stimulation.
KW - adaptive thermogenesis
KW - brown adipose tissue
KW - lipolysis
KW - Obesity
KW - β adrenergic receptor
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U2 - 10.1530/JOE-16-0199
DO - 10.1530/JOE-16-0199
M3 - Article
C2 - 27672060
AN - SCOPUS:85004178518
SN - 0022-0795
VL - 231
SP - 259
EP - 269
JO - Journal of Endocrinology
JF - Journal of Endocrinology
IS - 3
ER -