Progenitor-like characteristics in a subgroup of UCP1+ cells within white adipose tissue

Thermogenic beige fat found in white adipose tissue is a potential therapeutic target to curb the global obesity and diabetes epidemic. However, these inducible thermogenic beige adipocytes have been thought to be short-lived and rapidly convert to “white-like” adipocytes after discontinuing stimuli. In this study, using effective labelling techniques and genetic mouse tools, we demonstrated that a subset of UCP1+ cells that exist within white adipose tissue are able to self-divide and contribute to new beige adipocyte recruitment in response to β3 stimuli. When these cells were depleted or their adipogenic capability was blocked, β3-induced beige adipocyte formation was impaired. We also identified a cell cycle machinery of p21 and CDKN2A as a molecular basis of beige adipocyte regulation. Collectively, our findings provide new insights into the cellular and molecular mechanisms of beige adipocyte regulation and potentially therapeutic opportunities to induce beige phenotype and treat metabolic disease.