Activation of AMP-Activated Protein Kinase Attenuates Tumor Necrosis Factor-alpha-Induced Lipolysis via Protection of Perilipin in 3T3-L1 Adipocytes.
10.3803/EnM.2014.29.4.553
- Author:
Seok Woo HONG
1
;
Jinmi LEE
;
Se Eun PARK
;
Eun Jung RHEE
;
Cheol Young PARK
;
Ki Won OH
;
Sung Woo PARK
;
Won Young LEE
Author Information
1. Institute of Medical Research, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
AMP-activated protein kinases;
Lipolysis;
Perilipin;
PERK/eIF2alpha;
Adipocytes
- MeSH:
2-Aminopurine;
Adipocytes*;
AMP-Activated Protein Kinases*;
Blotting, Western;
Endoplasmic Reticulum;
Fluorescent Antibody Technique;
Lipolysis*;
Necrosis*;
Phosphorylation;
Phosphotransferases;
Prokaryotic Initiation Factor-2;
Protein Kinases;
Tumor Necrosis Factor-alpha;
Unfolded Protein Response
- From:Endocrinology and Metabolism
2014;29(4):553-560
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: Tumor necrosis factor (TNF)-alpha and AMP-activated protein kinase (AMPK) are known to stimulate and repress lipolysis in adipocytes, respectively; however, the mechanisms regulating these processes have not been completely elucidated. METHODS: The key factors and mechanism of action of TNF-alpha and AMPK in lipolysis were investigated by evaluating perilipin expression and activity of protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic initiation factor 2 alpha (eIF2alpha) by Western blot and an immunofluorescence assay in 24-hour TNF-alpha-treated 3T3-L1 adipocytes with artificial manipulation of AMPK activation. RESULTS: Enhancement of AMPK activity by the addition of activator minoimidazole carboxamide ribonucleotide (AICAR) suppressed TNF-alpha-induced lipolysis, whereas the addition of compound C, an inhibitor of AMPK phosphorylation, enhanced lipolysis. Perilipin, a lipid droplet-associated protein, was decreased by TNF-alpha and recovered following treatment with AICAR, showing a correlation with the antilipolytic effect of AICAR. Significant activation of PERK/eIF2alpha, a component of the unfolded protein response signaling pathway, was observed in TNF-alpha or vesicle-treated 3T3-L1 adipocytes. The antilipolytic effect and recovery of perilipin expression by AICAR in TNF-alpha-treated 3T3-L1 adipocytes were significantly diminished by treatment with 2-aminopurine, a specific inhibitor of eIF2alpha. CONCLUSION: These data indicated that AICAR-induced AMPK activation attenuates TNF-alpha-induced lipolysis via preservation of perilipin in 3T3-L1 adipocytes. In addition, PERK/eIF2alpha activity is a novel mechanism of the anti-lipolytic effect of AICAR.
