期刊
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
卷 138, 期 -, 页码 376-383出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jsbmb.2013.07.005
关键词
Orexin A; GLUT4; Adipocytes; PPAR gamma
资金
- National Natural Science Foundation of China [30872724, 81071460, 81271996]
- Natural Science Foundation of Liaoning Province [201202292]
Orexin A regulates food intake, energy metabolism and gastrointestinal function; it also increases glucose uptake and inhibits lipolysis, suggesting a role for orexin A in glucose and lipid metabolism. In this study, the effects of orexin A on glucose transporter 4 (GLUT4) mRNA level and lipid content were explored in 3T3-L1 preadipocytes and adipocytes. Orexin receptor 1 (OX1R) protein expression was determined in the adipose tissue of normal and obese rats. In addition, 3T3-L1 preadipocytes and differentiated 3T3-L1 adipocytes were incubated with different concentrations of orexin A (10(-9) to 10(-7) M), without or with OX1R specific antagonist, then the peroxisome proliferator-activated receptor-gamma 2 (PPAR gamma 2) mRNA expression was analyzed. Differentiated 3T3-L1 adipocytes were exposed to orexin A, without or with MAPK and OX1R antagonist, after which the GLUT4 and ERK1/2, JNK, and p38 MAPK activation, and triglyceride (TG) content were measured. We observed that OX1R protein expression was decreased in obese rats, and OX1R protein level was negatively correlated with body fat, Lee's index, TG, total cholesterol, and fasting insulin levels. Orexin A enhanced PPAR gamma 2 mRNA expression in a dose-dependent manner in 3T3-L1 preadipocytes through OX1R. In differentiated 3T3-L1 adipocytes, orexin A significantly increased GLUT4 mRNA levels, which was blocked by the ERK1/2, JNK, and p38 MAPK inhibitors as well as OX1R antagonist. Furthermore, orexin A increased cellular TG content via ERK1/2, JNK, and p38 MAPK as well as OX1R. Thus, orexin A increases GLUT4 mRNA expression and lipid accumulation in differentiated 3T3-L1 adipocytes via ERK1/2, JNK, and p38 MAPK signaling. In addition, orexin A increases PPAR gamma 2 mRNA expression in 3T3-L1 preadipocytes. Further studies are necessary to elucidate the impact of orexin A in metabolic disorders and adipocyte differentiation. Crown Copyright (C) 2013 Published by Elsevier Ltd. All rights reserved.
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