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

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.

Abbreviations: ACC, acetyl-CoA carboxylase, ADRP, adipose differentiation-related protein, AICAR, 5-aminoimidazole-4-carboxamide ribonucleoside, AMPK, AMP-activated protein kinase, ApoB, apolipoprotein B, FAS, fatty acid synthase, GAPDH, glyceraldehyde-3-phosphate dehydrogenase, HMGCR, 3-hydroxy-3-methylglutaryl CoA reductase, MSW, mainstream whole, MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, a tetrazole, SREBPs, sterol-regulated element-binding proteins, SSW, sidestream whole, LDLR, low density lipopotein receptor, NAFLD, non-alcoholic fatty liver diseases, TPM, total particulate matter, TG, triglyceride, TC, total cholesterol

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