title: Alpha-lipoic acid attenuates adipocyte differentiation and lipid accumulation in 3T3-L1 cells via AMPK-dependent autophagy.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: 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.
authors: Jong Ryeal
authors: JR
authors: Hahm
authors: 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.
authors: Hae Sook
authors: HS
authors: Noh
authors: 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.
authors: Ji Hye
authors: JH
authors: Ha
authors: 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.
authors: Gu Seob
authors: GS
authors: Roh
authors: 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.
authors: Deok Ryong
authors: DR
authors: Kim
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects*; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects*; D051379:Mice; D008063:Thioctic Acid / Q000494:pharmacology*; D014617:Vacuoles / Q000187:drug effects / Q000378:metabolism
chemical_list: D000975:Antioxidants; D007328:Insulin; D008063:Thioctic Acid; D003907:Dexamethasone; D055372:AMP-Activated Protein Kinases; D015056:1-Methyl-3-isobutylxanthine
keywords: AMPK; Adipocyte differentiation; Autophagy; LC3-II; Lipid droplets; α-Lipoic acid