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Life Sci. 2014 Apr 1;100(2):125-32. doi: 10.1016/j.lfs.2014.02.001. Epub 2014 Feb 14.

Alpha-lipoic acid attenuates adipocyte differentiation and lipid accumulation in 3T3-L1 cells via AMPK-dependent autophagy.

Author information

1
Department of Internal Medicine, Gyeongsang National University, School of Medicine, JinJu 660-290, Republic of Korea; Institute of Health Sciences, Gyeongsang National University, School of Medicine, JinJu 660-290, Republic of Korea.
2
Department of Biochemistry, Gyeongsang National University, School of Medicine, JinJu 660-290, Republic of Korea; Institute of Health Sciences, Gyeongsang National University, School of Medicine, JinJu 660-290, Republic of Korea.
3
Department of Biochemistry, Gyeongsang National University, School of Medicine, JinJu 660-290, Republic of Korea; Department of Neurobiology, Gyeongsang National University, School of Medicine, JinJu 660-290, Republic of Korea.
4
Department of Anatomy, Gyeongsang National University, School of Medicine, JinJu 660-290, Republic of Korea; Department of Neurobiology, Gyeongsang National University, School of Medicine, JinJu 660-290, Republic of Korea; Institute of Health Sciences, Gyeongsang National University, School of Medicine, JinJu 660-290, Republic of Korea.
5
Department of Biochemistry, Gyeongsang National University, School of Medicine, JinJu 660-290, Republic of Korea; Department of Neurobiology, Gyeongsang National University, School of Medicine, JinJu 660-290, Republic of Korea; Institute of Health Sciences, Gyeongsang National University, School of Medicine, JinJu 660-290, Republic of Korea. Electronic address: drkim@gnu.ac.kr.

Abstract

AIMS:

During the adipocyte differentiation, some intracellular organelles are degraded and instead lipid droplets are gradually accumulated in the cytoplasm for energy storage. Autophagy, a self-eating process, has been implicated in the removal of intracellular components in adipogenesis, but its mechanism is poorly understood. In this work we examined how α-lipoic acid modulates the autophagic process during the adipocyte differentiation.

MAIN METHODS:

3T3-L1 pre-adipocytes were differentiated in the medium containing insulin, dexamethasone, and 1-methyl-3-isobutylxanthine. Lipid contents in adipocytes were determined by Oil-Red O staining. Autophagy was evaluated by Western blotting, accumulation of acidic vacuoles in cells.

KEY FINDINGS:

We observed that formation of LC3-II, an indicative marker for autophagy, was greatly down-regulated at the beginning stage of differentiation, but it was gradually increased with respect to earlier differentiation time. In addition, ATG5-12 conjugates were similarly produced, and acidic autophagic vacuoles were greatly elevated at the earlier stages of differentiation. Furthermore, α-lipoic acid deteriorated the intracellular accumulation of lipid droplets by blocking the production of acidic autophagic vacuoles, LC3-II, and other autophagy-related proteins during the adipocyte differentiation and influenced expression of adipocyte-stimulating factors. It also specifically suppressed activation of AMPK, an essential modulator for autophagy, at the earlier step of adipocyte differentiation.

SIGNIFICANCE:

These data suggest that α-lipoic acid significantly attenuates adipocyte differentiation via the direct modulation of intracellular degradation process and consequently decrease intracellular fat deposit of adipocytes.

KEYWORDS:

AMPK; Adipocyte differentiation; Autophagy; LC3-II; Lipid droplets; α-Lipoic acid

PMID:
24530288
DOI:
10.1016/j.lfs.2014.02.001
[Indexed for MEDLINE]

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