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

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

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 ( Adrb3 ) 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 Adrb 1, not Adrb3 , activation. Adrb 1 activation stimulates WAT resident perivascular ( Acta2 +) cells to form cold-induced beige adipocytes. In contrast, Adrb3 activation stimulates mature white adipocytes to convert into beige adipocytes. Necessity tests, using mature adipocyte-specific Prdm16 deletion strategies, demonstrated that adipocytes are required and are predominant source to generate Adrb3 -induced, but not cold-induced, beige adipocytes. Collectively, we identify that cold temperatures and Adrb3 agonists activate distinct cellular populations that express different β-adrenergic receptors to induce beige adipogenesis.

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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