EPIDERMAL GROWTH-FACTOR PROMOTES ADIPOGENESIS OF 3T3-L1 CELL IN-VITRO

We have reported the importance of epidermal growth factor (EGF) for t he induction of obesity in mice. In this study, we studied the effects of EGF on the induction of lipogenic enzymes and on the accumulation of triglyceride in a differentiated mouse adipocyte cell in vitro. Mou se 3T3-L1 preadipocytic cells differentiated into mature adipocytes af ter the differentiation procedure by insulin, dexamethasone, and methy lisobutyl-xanthine. I-125-EGF binding studies in the differentiated 3T 3-L1 cells showed specific I-125-EGF bindings, and they expressed gene transcripts for EGF receptors by reverse transcription and polymerase chain reaction at all differentiative stages examined. Although EGF s howed inhibitory effects on the triglyceride accumulation when adminis tered to the preadipocytic 3T3-L1 cells, EGF enhanced the adipogenesis in the differentiated cells in dose- and time-dependent manners. Admi nistration of EGF at 0.1-1 nM from 4 days after the differentiation pr ocedure for 10 days, significantly enhanced the acyl-Co A synthetase a nd lipoprotein lipase messenger RNA levels, both of which are rate-lim iting enzymes to synthesize triglyceride in adipocytes. Moreover, 0.1- 1 nM EGF increased the amounts of triglyceride accumulated in the cell s, in proportion to the acyl-Co A synthetase and lipoprotein lipase me ssenger RNA levels. EGF rather failed the adipogenesis at 10 nM. Time course studies revealed that 1 nM EGF significantly increased the intr acellular triglyceride levels from 4 through 16 days administration. T hese results suggest that EGF shows biphasic effects on adipocytes: al though EGF inhibits preadipocytes differentiation into mature adipocyt es, it promotes adipogenesis in the differentiated adipocytes.