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Activation of AMP-Activated Protein Kinase Attenuates Tumor Necrosis Factor-alpha-Induced Lipolysis via Protection of Perilipin in 3T3-L1 Adipocytes
Endocrinology and Metabolism ; : 553-560, 2014.
Article in English | WPRIM | ID: wpr-14697
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.
Subject(s)

Full text: Available Index: WPRIM (Western Pacific) Main subject: Phosphorylation / Phosphotransferases / Protein Kinases / Blotting, Western / Fluorescent Antibody Technique / Tumor Necrosis Factor-alpha / Adipocytes / Prokaryotic Initiation Factor-2 / Endoplasmic Reticulum / AMP-Activated Protein Kinases Language: English Journal: Endocrinology and Metabolism Year: 2014 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Phosphorylation / Phosphotransferases / Protein Kinases / Blotting, Western / Fluorescent Antibody Technique / Tumor Necrosis Factor-alpha / Adipocytes / Prokaryotic Initiation Factor-2 / Endoplasmic Reticulum / AMP-Activated Protein Kinases Language: English Journal: Endocrinology and Metabolism Year: 2014 Type: Article