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The Mitogenic and Antiapoptotic Actions of Ghrelin in 3T3-L1 Adipocytes

Department of Internal Medicine (C.Y.Y., Y.J.P., C.S.S., S.Y.K., H.K.L., K.S.P.) Seoul National University College of Medicine, Seoul 110-744, Korea; Department of Internal Medicine (M.S.K., J.Y.P., K.U.L.), and Asan Institute for Life Sciences (P.G.J., H.S.P., J.W.R., Y.K.P.), University of Ulsan College of Medicine, Seoul 138-736, Korea; and Medicine-Endocrine (Y.B.K.), Beth Israel Deaconess Medical Center Harvard Medical School, Boston, Massachusetts 02215

Address all correspondence and requests for reprints to: Kyong Soo Park, M.D. Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-744, Korea. E-mail: kspark{at}snu.ac.kr.

Ghrelin, a stomach-derived hormone, induces adiposity when administered to rodents. Because ghrelin receptor is abundantly expressed in adipose tissue, we investigated the role of ghrelin in adipocyte biology. We observed ghrelin receptor expression in 3T3-L1 preadipocytes and adipocytes. Treatment of preadipocytes with ghrelin induced cellular proliferation and differentiation to mature adipocytes, as well as basal and insulin-stimulated glucose transport, but it inhibited adipocyte apoptosis induced by serum deprivation. Exposure of 3T3-L1 cells to ghrelin caused a rapid activation of MAPKs, especially ERK1/2. Chemical inhibition of MAPK blocked the mitogenic and antiapoptotic effects of ghrelin. Ghrelin also stimulated the insulin receptor substrate-associated phosphatidylinositol 3-kinase/Akt pathway in 3T3-L1 preadipocytes and adipocytes, whereas inhibition of this pathway blocked the effects of ghrelin on cell proliferation, antiapoptosis and glucose uptake. These findings suggest that the direct effects of ghrelin on proliferation, differentiation, and apoptosis in adipocytes may play a role in regulating fat cell number. These effects may be mediated via activation of the MAPK and phosphatidylinositol 3-kinase/Akt pathways.

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