Thermal stress induces glycolytic beige fat formation via a myogenic state.

Abstract

Environmental cues profoundly affect cellular plasticity in multicellular organisms. For instance, exercise promotes a glycolytic-to-oxidative fiber-type switch in skeletal muscle, and cold acclimation induces beige adipocyte biogenesis in adipose tissue. However, the molecular mechanisms by which physiological or pathological cues evokes developmental plasticity remain insufficiently understood. Here, we report a previously uncharacterized form of beige adipocytes that play a critical role in cold adaptation in the absence of β-adrenergic receptor (β-AR) signaling. This unique beige fat possesses distinct characteristics from the conventional beige fat in their developmental origin, regulation, and enhanced glucose oxidation; hence, we refer to them as glycolytic beige fat (g-beige). Mechanistically, we identify GA-binding protein alpha (GABPα) that controls g-beige adipocyte differentiation through a myogenic intermediate. Our study uncovers a non-canonical adaptive mechanism by which thermal stress induces progenitor cell plasticity and recruits a distinct form of thermogenic cells required for energy homeostasis and survival.