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

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.