Second-hand smoke stimulates lipid accumulation in the liver by modulating AMPK and SREBP-1☆

Received 23 September 2008; received in revised form 25 February 2009; accepted 14 March 2009. published online 18 May 2009.

Refers to article:

Cigarette smoke exposure: A novel cofactor of NAFLD progression? , 10 June 2009
Ariane Mallat, Sophie Lotersztajn
Journal of Hepatology
September 2009 (Vol. 51, Issue 3, Pages 430-432)
Full Text | Full-Text PDF (94 KB)

Background/Aims

The underlying mechanisms of steatosis, the first stage of non-alcoholic fatty liver disease (NAFLD) that is characterized by the accumulation of lipids in hepatocytes, remain unclear. Our study aimed to investigate the hypothesis that cigarette smoke is known to change circulating lipid profiles and thus may also contribute to the accumulation of lipids in the liver.

Methods

Mice and cultured hepatocytes were exposed to sidestream whole smoke (SSW), a major component of “second-hand” smoke and a variety of cellular and molecular approaches were used to study the effects of cigarette smoke on lipid metabolism.

Results

SSW increases lipid accumulation in hepatocytes by modulating the activity of 5′-AMP-activated protein kinase (AMPK) and sterol response element binding protein-1 (SREBP-1), two critical molecules involved in lipid synthesis. SSW causes dephosphorylation/ inactivation of AMPK, which contributes to increased activation of SREBP-1. These changes of activity lead to accumulation of triglycerides in hepatocytes.

Conclusion

These novel findings are important because they point to another risk factor of smoking, i.e., that of contributing to NAFLD. In addition, our results showing that both AMPK and SREBP are critically involved in these effects of smoke point to the potential use of these molecules as targets for treatment of cigarette smoke-induced metabolic diseases.

Associate Editor: C.P. Day

Keywords: Kinases, Fatty liver, Non-alcoholic fatty liver diseases, Transcription factors, Sidestream whole smoke

1 Graduate Program in Cell, Molecular and Developmental Biology, University of California Riverside, Riverside, CA, USA

2 Division of Biomedical Sciences, University of California Riverside, Riverside, CA, USA

3 Department of Cell Biology and Neuroscience, University of California Riverside, 900 University Ave., Riverside, CA 92521, USA

Corresponding author. Tel.: +1 951 8272585; fax: +1 951 8274286.

☆ The underlying research reported in the study was funded by NIH (HL77448 and HL89940) and in part by the Tobacco-Related Disease Research Program TRDRP (11DT-0244). The authors who have taken part in this study declared that they do not have anything to disclose regarding funding from industry or conflict of interest with respect to this manuscript.

PII: S0168-8278(09)00253-0

doi:10.1016/j.jhep.2009.03.026

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