Disruption of beta3 adrenergic receptor increases susceptibility to DIO in mouse

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, Antonio C. Bianco, Miriam O. Ribeiro

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)259-269
Number of pages11
JournalJournal of Endocrinology
Volume231
Issue number3
DOIs
StatePublished - 2016
Externally publishedYes

Keywords

  • adaptive thermogenesis
  • brown adipose tissue
  • lipolysis
  • Obesity
  • β adrenergic receptor

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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