The mitogenic and antiapoptotic actions of ghrelin in 3T3-L1 adipocytes.
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.
Kim
Min Seon
MS
Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-744, Korea.
Yoon
Cho Ya
CY
Jang
Pil Geum
PG
Park
Young Joo
YJ
Shin
Chan Soo
CS
Park
Hye Sun
HS
Ryu
Je Won
JW
Pak
Youngmi Kim
YK
Park
Joong Yeol
JY
Lee
Ki Up
KU
Kim
Seong Yeon
SY
Lee
Hong Kyu
HK
Kim
Young Bum
YB
Park
Kyong Soo
KS
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001692:Biological Transport / Q000187:drug effects; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D015870:Gene Expression; D054439:Ghrelin; D005947:Glucose / Q000378:metabolism; D051379:Mice; D036361:Peptide Hormones / Q000494:pharmacology* / Q000502:physiology; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D054440:Receptors, Ghrelin
D054439:Ghrelin; D036361:Peptide Hormones; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; D017853:Phosphotransferases (Alcohol Group Acceptor); D005947:Glucose