Introduction and Objective: E-cigarette use has become highly popular among youth and adults. This study examined how electronic cigarette exposure alters the serum proteome in mice and explored the role of nicotine-induced lipolysis in these changes. We have observed impaired cardiac function and increased oxidative stress following e-cigarette exposure. We hypothesized that lipolysis triggers systemic proteomic remodeling that promotes cardiometabolic dysfunction. Methods: High-fat-fed C57BL/6J mice were exposed for 12 weeks to saline aerosols, e-cigarette aerosols (2.4% nicotine) e-cig (2.4%, or e-cigarette (2.4%) + acipimox e-cig 2.4% + ACIP. Serum proteins were quantified by label-free LC-MS/MS and analyzed using primary component analysis (PCA), volcano plots, heatmaps, and enrichment workflows. Results: The PCA showed the e-cig (2.4%) group was clustered separately from the e-cig (2.4%) + ACIP and saline groups, indicating that e-cig (2.4%) induced a transcriptomic shift. We identified proteins altered by e-cigarette exposure and normalized with acipimox. Rescued proteins included PON1, FLT4, APOD, and SOD3, linking oxidative stress, lipid metabolism, and inflammation to systemic cardiometabolic risk. PON1 is an HDL-associated lipolactonase. E-cigarette decreased PON1 expression, and these changes were normalized with acipimox. SOD3, an extracellular antioxidant enzyme that mitigates cardiovascular oxidative stress, was similarly reduced and rescued, supporting the notion that redox dysregulation is a central mechanism. APOD, a lipocalin-family apolipoprotein involved in lipid metabolism and cardiometabolic regulation, was downregulated and subsequently restored, indicating disrupted lipid transport that is reversible by inhibiting lipolysis Conclusion: These findings are consistent with lipolysis-linked disruption of redox and lipid homeostasis, which could promote metabolic disease, highlighting a possible mechanism of how nicotine hampers diabetes management. Disclosure F. Marquez Romero: None. J. Xu: None. N. Kubiak: None. E.I. Panem: None. K.M. Hasan: None. J. Rivera: None. X.M. Shao: None. T.C. Friedman: Advisory Panel; Ended; Acella Pharmaceuticals. J. Espinoza-Derout: None. Funding JE-D work was supported by the NIH grants: NIGMS (R16GM153622), NIMHD (S21MD000103), the CDU Accelerating Excellence in Translational Science (AXIS) (U54MD007598-14S2), and a voucher from UCLA CTSI (UL1TR001881). TF was supported by the California TRDRP grant (28CP-0040), DODCDMRP grant (PR190942) and NIDA (R25DA050723) grants. X.M.S was supported by a NIDA (R42DA044788) grant.
ROMERO et al. (Fri,) studied this question.