Disruption of beta3 adrenergic receptor increases susceptibility to DIO in mouse.
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 ARβ3isoform in this process. This study focused on the ARβ3knockout 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, ARβ3inactivation does not affect BAT thermogenesis but increases susceptibility to diet-induced obesity by dampening WAT lipolytic response to adrenergic stimulation.
Center of Biological and Health SciencesMackenzie Presbyterian University, Sao Paulo, SP, Brazil.|Department of Translational MedicineEPM, Federal University of Sao Paulo, Sao Paulo, SP, Brazil.
Nailliw Z
NZ
Preite
Center of Biological and Health SciencesMackenzie Presbyterian University, Sao Paulo, SP, Brazil.|Department of Translational MedicineEPM, Federal University of Sao Paulo, Sao Paulo, SP, Brazil.
Bruna P P do
BP
Nascimento
Experimental Pathophysiology DepartmentFaculty of Medicine, University of Sao Paulo, SP, Brazil.
Cynthia R
CR
Muller
Experimental Pathophysiology DepartmentFaculty of Medicine, University of Sao Paulo, SP, Brazil.
Anna Laura V
AL
Américo
School of ArtsSciences and Humanities, University of Sao Paulo, Sao Paulo, SP, Brazil.
Talita S
TS
Higa
School of ArtsSciences and Humanities, University of Sao Paulo, Sao Paulo, SP, Brazil.
Fabiana S
FS
Evangelista
Department of PathologySchool of Medical Sciences, Santa Casa, São Paulo, SP, Brazil.
Carmen L
CL
Lancellotti
Laboratory of Adipose Tissue BiologyIntegrated Group of Biotechnology, University of Mogi das Cruzes, Mogi das Cruzes, SP, Brazil.
Felipe dos Santos
FS
Henriques
Laboratory of Adipose Tissue BiologyIntegrated Group of Biotechnology, University of Mogi das Cruzes, Mogi das Cruzes, SP, Brazil.
Miguel Luiz
ML
Batista
Division of Endocrinology and MetabolismDepartment of Internal Medicine, Rush University and Medical Center, Chicago, Illinois, USA.
Antonio C
AC
Bianco
Center of Biological and Health SciencesMackenzie Presbyterian University, Sao Paulo, SP, Brazil miriamribeiro@mackenzie.br.
Miriam O
MO
Ribeiro
D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism; D052436:Adipose Tissue, White / Q000378:metabolism; D050154:Adiposity; D000818:Animals; D003080:Cold Temperature; D059305:Diet, High-Fat / Q000009:adverse effects; D050356:Lipid Metabolism; D008066:Lipolysis; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009638:Norepinephrine / Q000494:pharmacology; D009765:Obesity / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D022702:Receptors, Adrenergic, beta-3 / Q000172:deficiency* / Q000235:genetics; D022722:Thermogenesis
D022702:Receptors, Adrenergic, beta-3; D009638:Norepinephrine
adaptive thermogenesis; brown adipose tissue; lipolysis; obesity; β3 adrenergic receptor
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