Distinct cellular and molecular mechanisms for β3 adrenergic receptor-induced beige adipocyte formation.

Abstract

Beige/brite adipocytes are induced within white adipose tissues (WAT) and, when activated, consume glucose and fatty acids to produce heat. Classically, two stimuli have been used to trigger a beiging response: cold temperatures and β3-adrenergic receptor (<i>Adrb3</i>) agonists. These two beiging triggers have been used interchangeably but whether these two stimuli may induce beiging differently at cellular and molecular levels remains unclear. Here, we found that cold-induced beige adipocyte formation requires <i>Adrb</i>1, not <i>Adrb3</i>, activation. <i>Adrb</i>1 activation stimulates WAT resident perivascular (<i>Acta2</i>+) cells to form cold-induced beige adipocytes. In contrast, <i>Adrb3</i> activation stimulates mature white adipocytes to convert into beige adipocytes. Necessity tests, using mature adipocyte-specific <i>Prdm16</i> deletion strategies, demonstrated that adipocytes are required and are predominant source to generate <i>Adrb3</i>-induced, but not cold-induced, beige adipocytes. Collectively, we identify that cold temperatures and <i>Adrb3</i> agonists activate distinct cellular populations that express different β-adrenergic receptors to induce beige adipogenesis.