In spite of the widespread use of electronic cigarettes, also known as e-cigarettes, and the proposed adverse cardiac effects of
nicotine, the detrimental effects of e-cigarettes on the heart are not well known. This study examines the detrimental effects of e-cigarettes with
nicotine at doses that yield circulating
nicotine and
cotinine in the ranges similar to the levels found in habitual smokers, and a high fat diet (HFD) on cardiac structure and function in a commonly used model of diet-induced
obesity (DIO). C57BL/6J mice on an HFD were exposed to e-cigarette in the presence (2.4%
nicotine) or absence (0%
nicotine) of
nicotine and saline
aerosol for 12 weeks. Echocardiographic data demonstrated a decrease in left ventricular (LV) fractional shortening, LV ejection fraction, and velocity of circumferential fiber shortening (VCF) in mice treated with e-cigarette (2.4%
nicotine) compared to e-cigarette (0%
nicotine) or saline exposed mice. Cardiomyocytes (CMs) of mice treated with e-cigarette (2.4%
nicotine) exhibited LV abnormalities, including
lipid accumulation (ventricular steatosis), myofibrillar derangement and destruction, and mitochondrial hypertrophy, as revealed by transmission electron microscopy. The detrimental effects of e-cigarettes (2.4%
nicotine) on cardiac structure and function was accompanied by increased oxidative stress, plasma
free fatty acid levels, CM apoptosis, and inactivation of
AMP-activated protein kinase and activation of its downstream target,
acetyl-CoA-carboxylase. Our results indicate profound adverse effects of e-cigarettes (2.4%
nicotine) on the heart in obese mice and raise questions about the safety of the
nicotine e-cigarettes use.