Activation of the nuclear receptor peroxisome proliferator-activated gamma promotes brown adipocyte differentiation

Brown adipose tissue (BAT) functions in non-shivering and diet-induced thermogenesis via its capacity for uncoupled mitochondrial respiration. BAT dysfunction in rodents is associated with severe defects in energy homeostasis, resulting in obesity and hyperglycemia. Here, we report that the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR gamma), a prostaglandin-activated transcription factor recently implicated as a central regulator of white adipose tissue differentiation, also regulates brown adipocyte function. PPAR gamma is abundantly expressed in both embryonic and adult BAT. Treatment of CD-1 rats with the PPAR gamma-selective ligand BRL49653, an anti-diabetic drug of the thiazolidinedione class, results in marked increases in the mass of interscapular BAT. In vitro, BRL49653 induces the terminal differentiation of the brown preadipocyte cell line HIB-1B as judged by both changes in cell morphology and expression of uncoupling protein and other adipocyte-specific mRNAs. These data demonstrate that PPAR gamma is a key regulatory factor in brown adipocytes and suggest that PPAR gamma functions not only in the storage of excess energy in white adipose tissue but also in its dissipation in BAT.