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

Life Sci. 2014 Apr 1;100(2):125-132. doi: 10.1016/j.lfs.2014.02.001. Epub 2014 Feb 14.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-3-isobutylxanthine / pharmacology
  • 3T3-L1 Cells
  • AMP-Activated Protein Kinases / metabolism*
  • Adipocytes / cytology*
  • Adipocytes / drug effects
  • Adipocytes / metabolism
  • Adipogenesis / drug effects*
  • Animals
  • Antioxidants / pharmacology
  • Autophagy / drug effects*
  • Blotting, Western
  • Cell Differentiation / drug effects*
  • Dexamethasone / pharmacology
  • Insulin / pharmacology
  • Lipid Metabolism / drug effects*
  • Mice
  • Thioctic Acid / pharmacology*
  • Vacuoles / drug effects
  • Vacuoles / metabolism


  • Antioxidants
  • Insulin
  • Thioctic Acid
  • Dexamethasone
  • AMP-Activated Protein Kinases
  • 1-Methyl-3-isobutylxanthine