SAT639 Electronic Cigarettes-exposed Mice Have Impairments In Skeletal Muscle Mediated By Impaired Ampk Activation

Abstract

Abstract Disclosure: J. Rivera: None. J. Espinoza-Derout: None. K.M. Hasan: None. C. Lao: None. J.B. Wilson: None. X.M. Shao: None. Y. Tintut: None. M. Jordan: None. K.P. Roos: None. A.P. Sinha-Hikim: None. T.C. Friedman: None. Electronic cigarettes (E-Cig) are a relatively new way to deliver nicotine (Nic). E-Cigs are gaining popularity, especially among youth and young adults, who do not realize their harmful health effects. Our laboratory has been a pioneer in demonstrating the adverse effects of E-Cigs on the liver and the heart. Skeletal muscle is a bigger tissue with physical and metabolic importance fundamental for human health. We previously reported that IP injection of Nic with a “second-hit” such as a high-fat diet (HFD) caused skeletal muscle damage. This study evaluated the detrimental effects of E-Cigs administration on skeletal muscle. We used an E-Cig inhalation model to deliver Nic in a similar way to humans. C57BL6 mice were fed with an HFD, divided into three groups, and exposed to a saline solution (control group), commercially available E-Cig (bluCig) in absence of Nic (E-Cig 0%), or E-Cig with the presence of Nic (E-Cig 2.4%) for 12 weeks. Results showed that the skeletal muscle exposed to E-Cig 2.4% had a reduction of the phosphorylation of the metabolic regulator, AMPK, and the pro-lipolytic enzyme ATGL as measured by western blot analyses in relation to control saline and E-Cig 0% groups. This metabolic impairment was accompanied by a reduction of the homeostatic mechanism, autophagy by a decrease of the ratio LC3II/LC3I, in the group exposed to E-Cig 2.4% in relation to the saline group. Electron microscopy showed intramyofibrillar mitochondrial with cristolysis, vacuolization, and intramyocellular lipid deposits in the E-Cig 2.4% group. Additionally, we observed an increase in oxidative stress suggested by the increase of the antioxidant enzyme HO-1 in the E-Cig 2.4%, and the reduction of the protein levels of SOD1 and SOD2. Finally, the previous changes trigger the activation of cellular stress pathways such as the phosphorylation of p38 and the increase in inflammasome protein, Nrlp3 in the E-Cig 2.4% compared to the saline group. This study suggests skeletal muscle abnormalities in mice vaping E-Cig 2.4% can alter muscle health. We believe these abnormalities will have important consequences in the skeletal muscle considering the early life stage of the consumers. Presentation: Saturday, June 17, 2023