AMPK activation regulates apoptosis, adipogenesis, and lipolysis by eIF2α in adipocytes

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-AIC...

Full description

Saved in:
Bibliographic Details
Published in:Biochemical and biophysical research communications 2006-02, Vol.340 (1), p.43-47
Main Authors: Dagon, Yossi, Avraham, Yosefa, Berry, Elliot M.
Format: Article
Language:English
Subjects:
2-Aminopurine
Adipocyte
AICAR
AMPK
Apoptosis
C/EBPα
eIF2α
F442a
Lipolysis
PPARγ
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 (PPARγ) and CCAAT/enhancer-binding protein alpha (C/EBPα). We have identified the α-subunit of the eukaryotic initiation factor-2 (eIF2α) 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 eIF2α kinases, could overcome the apoptotic effect of AICAR, abolishing the reduction of PPARγ and C/EBPα and the lipolytic properties of AMPK. Thus, AMPK may diminish adiposity via reduction of fat cell number through eIF2α-dependent translation shutdown.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2005.11.159