AMPK activation regulates apoptosis, adipogenesis, and lipolysis by eIF2{alpha} in adipocytes
- Department of Human Nutrition and Metabolism, Braun School of Public Health, Faculty of Medicine, Hebrew University, Hadassah Medical School (Israel)
AMP-activated protein kinase (AMPK) is a metabolic master switch regulating glucose and lipid metabolism. Recently, AMPK has been implicated in the control of adipose tissue content. Yet, the nature of this action is controversial. We examined the effect on F442a adipocytes of the AMPK activator-AICAR. Activation of AMPK induced dose-dependent apoptotic cell death, inhibition of lipolysis, and downregulatation key adipogenic genes, such as peroxisome proliferator-activated receptor (PPAR{gamma}) and CCAAT/enhancer-binding protein alpha (C/EBP{alpha}). We have identified the {alpha}-subunit of the eukaryotic initiation factor-2 (eIF2{alpha}) as a target gene which is phosphorylated following AICAR treatment. Such phosphorylation is one of the best-characterized mechanisms for downregulating protein synthesis. 2-Aminopurine (2-AP), an inhibitor of eIF2{alpha} kinases, could overcome the apoptotic effect of AICAR, abolishing the reduction of PPAR{gamma} and C/EBP{alpha} and the lipolytic properties of AMPK. Thus, AMPK may diminish adiposity via reduction of fat cell number through eIF2{alpha}-dependent translation shutdown.
- OSTI ID:
- 20798774
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 340, Issue 1; Other Information: DOI: 10.1016/j.bbrc.2005.11.159; PII: S0006-291X(05)02711-7; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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