Disruption of beta3 adrenergic receptor increases susceptibility to DIO in mouse

Abstract

The brown adipose tissue (BAT) mediates adaptive changes in metabolic rate by responding to the sympathetic nervous system through beta-adrenergic receptors (AR). Here, we wished to define the role played by the AR beta(3) isoform in this process. This study focused on the AR beta(3) knockout mice (AR beta 3KO), including responsiveness to cold exposure, diet-induced obesity, intolerance to glucose, dyslipidaemia and lipolysis in white adipose tissue (WAT). AR beta 3KO mice defend core temperature during cold exposure (4 degrees C for 5h), with faster BAT thermal response to norepinephrine (NE) infusion when compared with wild-type (WT) mice. Despite normal BAT thermogenesis, AR beta 3KO 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 AR beta 3KO animals when compared with WT controls. Isoproterenol-induced lipolysis in isolated white adipocytes as assessed by glycerol release was significantly impaired in AR beta 3KO animals despite normal expression of key proteins involved in lipid metabolism. In conclusion, AR beta(3) inactivation does not affect BAT thermogenesis but increases susceptibility to diet-induced obesity by dampening WAT lipolytic response to adrenergic stimulation.