The Role of Fatty Acid Metabolism and Apolipoproteins in Ths-InducedHepatic Steatosis in Mice

Abstract

Background: Hepatic steatosis results from the increase of accumulation of lipids in the liver, decrease of beta fatty acid oxidation and/or decrease in the export to peripheral tissue by apolipoproteins. Previously, we showed that third hand smoke (THS) toxins result in hepatic steatosis in mice. Objective: The goal of this paper was two-fold: (1) To determine whether THS toxins alter key molecules involved in beta fatty acid metabolism and (2) to determine whether the levels of apolipoprotein B is decreased in THS-exposed mice leading to decrease export of lipid from the liver. Methodology: Mice were exposed to THS toxins for 6 months before performing the studies shown here. THS-exposed mice were also placed on western diet (WD) for five months or treated with AICAR to determine how THS-toxins affect the lipid metabolism of these animals. Results: THS-exposed mice do not show significant difference in the levels of key fatty acid metabolism enzymes (CPT1, ACC, IDH2 and LCAD) compared to the control, suggesting THS toxins do not decrease the levels of these enzymes. THS-exposed mice have lower levels of SIRT3 and ATP. These mice also have lower IDH2 activity. THS-exposed mice also have lower levels of apolipoprotein B compared to control, suggesting the excess fatty acids, which are converted to TG in the liver, are not being transported to peripheral tissue for usage or storage. Conclusion: These results suggest that even though THS toxins do not alter the levels of fatty acid metabolism enzymes, exposure result in lower levels of SIRT3 and lower IDH2 activity resulting in lower production of ATP in THS-exposed mice. THS toxins exposure also decrease of transport of lipids out of the liver by decreasing the levels of apolipoprotein B. Consequently, THS-exposed mice have an increase in lipid accumulation in the liver resulting in hepatic steatosis.