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

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 () 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 1, not , activation. 1 activation stimulates WAT resident perivascular (+) cells to form cold-induced beige adipocytes. In contrast, activation stimulates mature white adipocytes to convert into beige adipocytes. Necessity tests, using mature adipocyte-specific deletion strategies, demonstrated that adipocytes are required and are predominant source to generate -induced, but not cold-induced, beige adipocytes. Collectively, we identify that cold temperatures and agonists activate distinct cellular populations that express different β-adrenergic receptors to induce beige adipogenesis.