INHIBITION OF ADIPOGENESIS THROUGH MAP KINASE-MEDIATED PHOSPHORYLATION OF PPAR-GAMMA

Adipocyte differentiation is an important component of obesity and oth er metabolic diseases. This process is strongly inhibited by many mito gens and oncogenes. Several growth factors that inhibit fat cell diffe rentiation caused mitogen-activated protein (MAP) kinase-mediated phos phorylation of the dominant adipogenic transcription factor peroxisome proliferator-activated receptor gamma (PPAR gamma) and reduction of i ts transcriptional activity. Expression of PPAR gamma with a nonphosph orylatable mutation at this site (serine-112) yielded cells with incre ased sensitivity to ligand-induced adipogenesis and resistance to inhi bition of differentiation by mitogens. These results indicate that cov alent modification of PPAR gamma by serum and growth factors is a majo r regulator of the balance between cell growth and differentiation in the adipose cell lineage.