TRANSDIFFERENTIATION OF MYOBLASTS BY THE ADIPOGENIC TRANSCRIPTION FACTORS PPAR-GAMMA AND C EBP-ALPHA/

Skeletal muscle and adipose tissue development often has a reciprocal relationship in vivo, particularly in myodystrophic states. We have in vestigated whether determined myoblasts with no inherent adipogenic po tential can be induced to transdifferentiate into mature adipocytes by the ectopic expression of two adipogenic transcription factors, PPAR gamma and C/EBP alpha. When cultured under optimal conditions for musc le differentiation, murine G8 myoblasts expressing PPAR gamma and C/EB P alpha show markedly reduced levels of the myogenic basic helix-loop- helix proteins MyoD, myogenin, MRF4, and myf5 and are completely unabl e to differentiate into myotubes. Under conditions permissive for adip ogenesis including a PPAR activator, these cells differentiate into ma ture adipocytes that express molecular markers characteristic of this lineage. Our results demonstrate that a developmental switch between t hese two related but highly specialized cell types can be controlled b y the expression of key adipogenic transcription factors. These factor s have an ability to inhibit myogenesis that is temporally and functio nally separate from their ability to stimulate adipogenesis.