Activation of PPAR? induces profound multilocularization of adipocytes in adult mouse white adipose tissues

We sought to determine the effects of activation of peroxisome proliferator-activated receptor-? (PPAR-?) on multilocularization of adipocytes in adult white adipose tissue (WAT). Male C57BL/6 normal, db/db, and ob/ob mice were treated with agonists of PPAR-?, PPAR-a, or ß3-adrenoceptor for 3 weeks. To distinguish multilocular adipocytes from unilocular adipocytes, whole-mounted adipose tissues were co-immunostained for perilipin and collagen IV. PPAR-? activation with rosiglitazone or pioglitazone induced a profound change of unilocular adipocytes into smaller, multilocular adipocytes in adult WAT in a time-dependent, dose-dependent, and reversible manner. PPAR-a activation with fenofibrate did not affect the number of locules or remodeling. db/db and ob/ob obese mice exhibited less multilocularization in response to PPAR-? activation compared to normal mice. Nevertheless, all adipocytes activated by PPAR-? contained a single nucleus regardless of locule number. Multilocular adipocytes induced by PPAR-? activation contained substantially increased mitochondrial content and enhanced expression of uncoupling protein-1, PPAR-? coactivator-1-a , and perilipin. Taken together, PPAR-? activation induces profound multilocularization and enhanced mitochondrial biogenesis in the adipocytes of adult WAT. These changes may affect the overall function of WAT.