ABSTRACT
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.
Subject(s)
Adipocytes/metabolism , Apoptosis/drug effects , Peptide Hormones/pharmacology , 3T3-L1 Cells , Adipocytes/chemistry , Adipocytes/drug effects , Animals , Biological Transport/drug effects , Cell Differentiation/physiology , Cell Proliferation/drug effects , Gene Expression , Ghrelin , Glucose/metabolism , Mice , Peptide Hormones/physiology , Phosphotransferases (Alcohol Group Acceptor)/physiology , RNA, Messenger/analysis , RNA, Messenger/metabolism , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/metabolism , Receptors, GhrelinABSTRACT
Ghrelin, a newly identified gut hormone, has been implicated in the regulation of food intake and energy homeostasis. This study was undertaken to investigate changes in expression levels of stomach ghrelin as well as of ghrelin receptor in the hypothalamus and pituitary glands according to feeding state. Stomach ghrelin mRNA levels were increased by 48 h fasting but decreased by re-feeding. The ghrelin receptor mRNA levels of 48 h fasted rats were 8 times higher in the hypothalamus and 3 times higher in the anterior pituitary gland than levels in fed rats. In summary, not only stomach ghrelin, but also hypothalamic ghrelin receptor mRNA expression, increased during a fast. Such as enhanced ghrelin receptor expression could contribute to the amplification of ghrelin action in a negative-energy balance state.
