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 respiratio n. BAT dysfunction in rodents is associated with severe defects in ene rgy homeostasis, resulting in obesity and hyperglycemia. Here, we repo rt that the nuclear receptor peroxisome proliferator-activated recepto r gamma (PPAR gamma), a prostaglandin-activated transcription factor r ecently implicated as a central regulator of white adipose tissue diff erentiation, also regulates brown adipocyte function. PPAR gamma is ab undantly expressed in both embryonic and adult BAT. Treatment of CD-1 rats with the PPAR gamma-selective ligand BRL49653, an anti-diabetic d rug of the thiazolidinedione class, results in marked increases in the mass of interscapular BAT. In vitro, BRL49653 induces the terminal di fferentiation of the brown preadipocyte cell line HIB-1B as judged by both changes in cell morphology and expression of uncoupling protein a nd other adipocyte-specific mRNAs. These data demonstrate that PPAR ga mma is a key regulatory factor in brown adipocytes and suggest that PP AR gamma functions not only in the storage of excess energy in white a dipose tissue but also in its dissipation in BAT.