Electronic Cigarette Exposure Induces Adverse Cellular Alterations in Skeletal Muscle in Male Mice Subjected to a High-Fat Diet

Electronic cigarettes (E-Cig) are a new way of delivering nicotine, gaining popularity among adolescents and young adults, who often do not realize their harmful effects. Although the adverse effects of E-Cigs on the liver and heart have been demonstrated, their effects on the skeletal muscle have not been well studied. In this study, we evaluated the skeletal muscle effects of E-Cig aerosol, delivered in a manner similar to human vaping, in a mouse model of obesity induced by a high-fat diet (HFD). C57BL/6 mice, fed either a normal chow diet (NCD) or HFD, were exposed to either saline aerosol control or aerosol generated from Blu PLUSTM containing 0% or 2.4% nicotine for 12 weeks. Mice fed an NCD were included to distinguish whether E-Cig effects on the skeletal muscle required the presence of obesity induced by an HFD. The soleus muscle, an oxidative muscle rich in mitochondria, was assessed by Western blotting, electron microscopy, and biochemical assays. An NCD group was included to assess the baseline effects of HFD-induced obesity, on the skeletal muscle. The skeletal muscle from HFD-fed mice exposed to E-Cig 2.4% had reduced levels of phospho-AMPK compared with saline and E-Cig 0% groups, while E-Cigs had no effect on NCD-fed mice. Levels of phospho-adipose triglyceride lipase were also reduced in both E-Cig 2.4% and 0% compared with the saline group. These metabolic protein impairments were accompanied by increased levels of oxidative stress and phospho-p38 MAPK. Deregulation of the autophagy markers, microtubule-associated protein 1A/1B-light chain 3 (LC3-I; inactive form) and LC3-II (active form), was also observed, evidenced by decreased levels of LC3-II, ratio LC3-II/LC3-I, and increased levels of p62. Transmission electron microscopy analysis showed that E-Cig 2.4% induced damage to mitochondrial structure compared with the saline or E-Cig 0% groups. These findings suggest that E-Cig exposure on HFD impairs the skeletal muscle, adding to the growing list of affected organs for ongoing regulatory efforts concerning nicotine-containing substances.