12582 Electronic-cigarette Exposure Induces Hyperglycemia With A Fibrotic Phenotype In Skeletal Muscle In Mice Subjected To A High-fat Diet

Abstract Disclosure: J. Rivera: None. J. Chavez: None. J. Espinoza-Derout: None. K.M. Hasan: None. X.M. Shao: None. A.P. Sinha-Hikim: None. T.C. Friedman: None. Obesity and electronic cigarette (e-cigarette) use are highly prevalent among youth in the USA. Indeed, young e-cigarette users report less physical activity, leading to a decline in quality of life. Recent studies show e-cigarettes reduce skeletal muscle (SkM) performance in mice; however, the underlying metabolic and SkM cellular effects are unclear. E-cigarettes plus a high-fat diet (HFD) increase mice lipolysis and plasma-free fatty acids. These harmful changes in the liver and heart are prevented by the lipolysis inhibitor Acipimox (Acip). As SkM plays a crucial role in metabolic and chronic disease prevention, understanding the impact of e-cigarettes and HFD on SkM is essential.We exposed C57BL6 mice to e-cigarette inhalation in a free-moving system to deliver 2.4% nicotine in a similar way to humans. Mice were fed with an HFD and divided into 3 groups: Saline (control), e-cigarette (bluCig), and e-cigarette plus Acip (rescue group) for 12 weeks. SkM uptakes 70-80% of the postprandial glucose, so we performed a glucose tolerance test. We found higher glycemia in the e-cigarette compared to the Saline group, while the e-cigarette plus Acip group showed improved glycemia. Histological analysis of SkM with Hematoxylin and eosin (HE) staining revealed large extracellular fibrotic structures in the group with e-cigarettes, suggesting fibrosis. Sirius Red (SR) stain identified collagen deposition. The SR quantification showed an increase in the collagen in the e-cigarette to the saline-exposed group without recovery in the e-cigarette plus Acip group. Fibrosis restricts the SkM hypertrophy. So we analyzed the insulin-like growth factor-1 (IGF-1) (a key anabolic factor) by RT-qPCR. The mRNA levels of IGF-1 were reduced in the SkM of e-cigarettes compared to the Saline group, without recovery of the Acip group. In SkM hypertrophy, Satellite cells (SCs) are stimulated by IGF-1 and SkM fibrosis can affect SCs by restricting them. So we analyzed by western blot the SCs through the transcriptional factor PAX7 (SC marker). We found PAX7 levels were lower in the e-cigarette compared with the Saline group without recovery in the Acip group. These findings suggest the detrimental effects of e-cigarettes on glycemia and SkM health in mice, with implications for long-term health outcomes, particularly among obese individuals and e-cigarette users. Further research is necessary for understanding these adverse effects and promoting youth health. GRANT SUPPORT: U54MD007598, SC2GM135127, U54MD007598-14S2, PR190942, DA050723, and R25DA050723 grants. Presentation: 6/3/2024