SUN-061 E-Cigarettes Alter Lipid Homeostasis and Cause Hepatic Steatosis in Diet-Induced Obesity

Abstract

The use of electronic nicotine delivery systems (ENDS), also known as e-cigarettes, containing a variety of e-liquids/e-juices, is increasing at an alarming rate among young adults. Many ENDS users and regulatory agencies assume that ENDS are safe, in spite of them containing nicotine which contributes to nonalcoholic fatty liver disease (NAFLD). Recently, using Apolipoprotein E null mouse on a Western diet, we demonstrated that ENDS trigger oxidative stress, activate hepatocyte apoptosis, and cause hepatic steatosis This study examines the harmful hepatic effects of ENDS employing a most commonly used model of diet-induced obesity and at nicotine dose levels that are similar to the clinically relevant concentrations found in habitual smokers. To this end, we exposed C57 BL6 mice fed high fat diet (HFD) to ENDS in the presence (2.4%) or absence (0%) of nicotine or saline aerosol for 12 weeks. Our results show that compared to saline or ENDS (0%), ENDS (2.4%) exposure significantly reduced body weight gain, triggered oxidative stress, increased hepatocyte apoptosis, and induced hepatic lipid accumulation. Mechanistically, ENDS (2.4%) induced hepatic steatosis was mediated by increased free fatty acid (FAA) together with inhibition of hepatic AMP-activated protein kinase (AMPK) and activation of its downstream target, acetyl-CoA-carboxylase (ACC). In addition, expression of silent information regulator 1 (Sirt1), an important regulator of lipid homeostasis, was reduced in ENDS (2.4%) treated livers compared to saline or ENDS (0%) exposed livers. We conclude that greater hepatic oxidative stress, increased FFA together with inhibition of AMPK and Sirt1 mediates ENDS (2.4%) plus HFD-induced hepatic steatosis. These results demonstrate profound adverse effects of ENDS (2.4%) on the liver and emphasizes a direct connection of nicotine to NAFLD. This is important information for regulatory agencies that regulate ENDS.