Dimethyl sulfoxide reduces hepatocellular lipid accumulation through autophagy induction

Young Mi Song, Sun Ok Song, Yong Keun Jung, Eun Seok Kang, Bong Soo Cha, Hyun Chul Lee, byungwan lee

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Induction of autophagy is known not only to regulate cellular homeostasis but also to decrease triglyceride accumulation in hepatocytes. The aim of this study is to investigate whether DMSO (dimethyl sulfoxide) has a beneficial role in free fatty acid-induced hepatic fat accumulation. In HepG2 cells, treatment with 0.5 mM palmitate for six hours significantly increased lipid and triglyceride (TG) accumulation, assessed by Oil-red O staining and TG quantification assay. Treatment with 0.01% DMSO for 16 h statistically reduced palmitate-induced TG contents. Pretreatment of 10 mM 3-methyladenine (3MA) for 2 h restored hepatocellular lipid contents, which were attenuated by treatment with DMSO. DMSO increased LC3-II conversion and decreased SQSTM1/p62 expression in a time and dose-dependent manner. In addition, the number of autophagosomes and autolysosomes, as seen under an electron microscopy, as well as the percentage of RFP-LAMP1 colocalized with GFPLC3 dots in cells transfected with both GFP-LC3 and RFP-LAMP1, as seen under a fluorescent microscopy, also increased in DMSO-treated HepG2 cells. DMSO also suppressed p-eIF2α/p- EIF2S1, ATF4, p-AKT1, p-MTOR and p-p70s6k/p-RPS6KB2 expression as assessed by western blotting. Knockdown of ATF4 expression using siRNA suppressed ATF4 expression and phosphorylation of AKT1, MTOR and RPS6KB2, but increased LC3-II conversion. DMSO reduced not only soluble but also insoluble mtHTT (mutant huntingtin aggregates) expressions, which were masked in the presence of autophagy inhibitor. DMSO, a kind of chemical chaperone, activated autophagy by suppressing ATF4 expression and might play a protective role in the development of fatty acid-induced hepatosteatosis.

Original languageEnglish
Pages (from-to)1085-1097
Number of pages13
JournalAutophagy
Volume8
Issue number7
DOIs
Publication statusPublished - 2012 Jan 1

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Autophagy
Dimethyl Sulfoxide
Lipids
Triglycerides
Palmitates
Hep G2 Cells
70-kDa Ribosomal Protein S6 Kinases
Nonesterified Fatty Acids
Small Interfering RNA
Microscopy
Hepatocytes
Electron Microscopy
Homeostasis
Fatty Acids
Western Blotting
Fats
Phosphorylation
Staining and Labeling
Liver

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Song, Y. M., Song, S. O., Jung, Y. K., Kang, E. S., Cha, B. S., Lee, H. C., & lee, B. (2012). Dimethyl sulfoxide reduces hepatocellular lipid accumulation through autophagy induction. Autophagy, 8(7), 1085-1097. https://doi.org/10.4161/auto.20260
Song, Young Mi ; Song, Sun Ok ; Jung, Yong Keun ; Kang, Eun Seok ; Cha, Bong Soo ; Lee, Hyun Chul ; lee, byungwan. / Dimethyl sulfoxide reduces hepatocellular lipid accumulation through autophagy induction. In: Autophagy. 2012 ; Vol. 8, No. 7. pp. 1085-1097.
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abstract = "Induction of autophagy is known not only to regulate cellular homeostasis but also to decrease triglyceride accumulation in hepatocytes. The aim of this study is to investigate whether DMSO (dimethyl sulfoxide) has a beneficial role in free fatty acid-induced hepatic fat accumulation. In HepG2 cells, treatment with 0.5 mM palmitate for six hours significantly increased lipid and triglyceride (TG) accumulation, assessed by Oil-red O staining and TG quantification assay. Treatment with 0.01{\%} DMSO for 16 h statistically reduced palmitate-induced TG contents. Pretreatment of 10 mM 3-methyladenine (3MA) for 2 h restored hepatocellular lipid contents, which were attenuated by treatment with DMSO. DMSO increased LC3-II conversion and decreased SQSTM1/p62 expression in a time and dose-dependent manner. In addition, the number of autophagosomes and autolysosomes, as seen under an electron microscopy, as well as the percentage of RFP-LAMP1 colocalized with GFPLC3 dots in cells transfected with both GFP-LC3 and RFP-LAMP1, as seen under a fluorescent microscopy, also increased in DMSO-treated HepG2 cells. DMSO also suppressed p-eIF2α/p- EIF2S1, ATF4, p-AKT1, p-MTOR and p-p70s6k/p-RPS6KB2 expression as assessed by western blotting. Knockdown of ATF4 expression using siRNA suppressed ATF4 expression and phosphorylation of AKT1, MTOR and RPS6KB2, but increased LC3-II conversion. DMSO reduced not only soluble but also insoluble mtHTT (mutant huntingtin aggregates) expressions, which were masked in the presence of autophagy inhibitor. DMSO, a kind of chemical chaperone, activated autophagy by suppressing ATF4 expression and might play a protective role in the development of fatty acid-induced hepatosteatosis.",
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Song, YM, Song, SO, Jung, YK, Kang, ES, Cha, BS, Lee, HC & lee, B 2012, 'Dimethyl sulfoxide reduces hepatocellular lipid accumulation through autophagy induction', Autophagy, vol. 8, no. 7, pp. 1085-1097. https://doi.org/10.4161/auto.20260

Dimethyl sulfoxide reduces hepatocellular lipid accumulation through autophagy induction. / Song, Young Mi; Song, Sun Ok; Jung, Yong Keun; Kang, Eun Seok; Cha, Bong Soo; Lee, Hyun Chul; lee, byungwan.

In: Autophagy, Vol. 8, No. 7, 01.01.2012, p. 1085-1097.

Research output: Contribution to journalArticle

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Song YM, Song SO, Jung YK, Kang ES, Cha BS, Lee HC et al. Dimethyl sulfoxide reduces hepatocellular lipid accumulation through autophagy induction. Autophagy. 2012 Jan 1;8(7):1085-1097. https://doi.org/10.4161/auto.20260