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Wang-Yang Xu, Yan Shen, Houbao Zhu, Junhui Gao, Chen Zhang, Lingyun Tang, Shun-Yuan Lu, Chun-Ling Shen, Hong-Xin Zhang, Ziwei Li, Peng Meng, Ying-Han Wan, Jian Fei and Zhu-Gang Wang

induce fat burning in response to stimuli ( Wu et al. 2012 , Shabalina et al. 2013 ). Chronic stimulation of β3 adrenergic receptor (β3AR) could convert WAT into a tissue resembling BAT, which was called ‘browning’ of white fat ( Seale et al. 2011

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Nailliw Z Preite, Bruna P P do Nascimento, Cynthia R Muller, Anna Laura V Américo, Talita S Higa, Fabiana S Evangelista, Carmen L Lancellotti, Felipe dos Santos Henriques, Miguel Luiz Batista Jr, Antonio C Bianco and Miriam O Ribeiro

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 diet-induced obesity by dampening WAT lipolytic response to adrenergic stimulation.

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Abdoulaye Diané, Nikolina Nikolic, Alexander P Rudecki, Shannon M King, Drew J Bowie and Sarah L Gray

M 2003 β3-Adrenergic receptor is involved in feeding regulation in chicks . Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology 135 403 – 409 . Tachibana T Oikawa D Adachi N Boswell T Furuse M 2007

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Cintia B Ueta, Gustavo W Fernandes, Luciane P Capelo, Tatiane L Fonseca, Flávia D'Angelo Maculan, Cecilia H A Gouveia, Patrícia C Brum, Marcelo A Christoffolete, Marcelo S Aoki, Carmen L Lancellotti, Brian Kim, Antonio C Bianco and Miriam O Ribeiro

( Collins & Surwit 2001 ). The critical role played by these receptors in BAT function and overall energy homeostasis is illustrated by the fact that mice with combined targeted disruption of the three β 1 , β 2 , and β 3 adrenergic receptors (TKO mice

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Gustavo W Fernandes, Cintia B Ueta, Tatiane L Fonseca, Cecilia H A Gouveia, Carmen L Lancellotti, Patrícia C Brum, Marcelo A Christoffolete, Antonio C Bianco and Miriam O Ribeiro

; (D) gene expression of β 1 and β 3 adrenergic receptors in mice kept on a chow or HFD in BAT (cross hatched (black and white), WT; white, ARβ 2 KO); (E) brown adipose tissue thermogenic response during infusion of DB of WT and ARKOβ 2 mice. Entries

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Asuka Mano-Otagiri, Hisayuki Ohata, Azusa Iwasaki-Sekino, Takahiro Nemoto and Tamotsu Shibasaki

adipocytes. BAT plays a major role in energy expenditure and non-shivering thermogenesis in rodents. Noradrenaline released from the sympathetic nerve endings in BAT binds to β 3 -adrenergic receptors on brown adipocytes and initiates intracellular breakdown

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Johanna L Barclay, Hadiya Agada, Christina Jang, Micheal Ward, Neil Wetzig and Ken K Y Ho

thermoneutrality and the response to adrenergic stimulation and cold. Studies using rodent cell lines have observed that GCs downregulated UCP1 and the β3 adrenergic receptor ( Adrb3 ), which is characteristically highly expressed in BAT ( Soumano et al . 2000

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Clara Lefranc, Malou Friederich-Persson, Roberto Palacios-Ramirez and Aurelie Nguyen Dinh Cat

) in response to stimuli such as cold exposure, exercise, fasting or specific drug treatments (SIRT1 activators and β3-adrenergic receptor (β3-AR) agonists) ( Cypess et al. 2015 , Stanford et al. 2015 , Li et al. 2017 , Thyagarajan & Foster

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Carsten T Herz and Florian W Kiefer

be sufficient to promote WAT browning in humans. β-adrenergic receptor agonists are among the most widely studied pharmacological agents that induce BAT function and browning of WAT. Drugs highly selective for human β 3 adrenergic receptors (AR

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Keiko Nakahara, Rieko Okame, Tetsuro Katayama, Mikiya Miyazato, Kenji Kangawa and Noboru Murakami

. Thermogenesis in brown adipose tissue (BAT) depends on activation and increased expression of β3-adrenergic receptors and the consequent up-regulation of uncoupling protein 1 (UCP1; Cannon & Nedergaard 2004 ). This activation is partially regulated by the