Introduction and Objective: Electronic cigarettes (e-cigs) have become the main tobacco product used by youth. Although the effects of conventional cigarette use have been studied, the metabolic effects of e-cigs have yet to be explored. In mice on a high-fat diet (HFD), we have shown that e-cig treatment produces cardiac dysfunction in a lipolysis-dependent manner. This e-cig-induced cardiac dysfunction is associated with oxidative stress and inflammatory markers that are normalized by acipimox.Methods: C57BL/6J mice on HFD were treated with saline, e-cig with 2.4% nicotine [e-cig (2.4%)], and e-cig (2.4%) plus acipimox [e-cig (2.4%)+ACIP], for 12 weeks. Serum samples were prepared with equiSPLASH lipidomics standards and extracted using the MMC one-phase method. The samples were analyzed by LC-MS/MS in both positive and negative ion modes. Datasets were processed with Principal Component Analysis (PCA), volcano plots, and heatmaps. Furthermore, Pathway Enrichment Analysis (PEA) associations were generated using lipid databases such as LipidMaps and analyzed using Lipid Set Enrichment Analysis (LSEA).Results: PCA shows a separation between e-cig (2.4%) and saline profiles in positive and negative modes. The e-cig (2.4%)+ACIP overlapped with the saline group, indicating a rescue effect. Lipidomic differential lipid analysis detected 149 altered lipids, including enrichment of ether-linked triacylglycerols, lysophosphatidylcholines, and saturated/odd-chain fatty acids. PEA found e-cig suppression of PLA2G hydrolysis, SCD1 activity, and LPCAT/PEMT activation. LSEA showed e-cig enrichment of lipotoxic classes, which were normalized by acipimox.Conclusion: Acipimox treatment restores PLA2G hydrolysis, SCD1 desaturation, and LPCAT/PEMT balance, mitigating e-cig-induced inflammation and oxidative stress markers. These experiments uncover lipolysis as a potential therapeutic target to counteract e-cig-induced cardiometabolic complications in diabetes and obesity.
E.I. Panem: None. J. Xu: None. N. Kubiak: None. F. Marquez Romero: None. K.M. Hasan: None. J. Rivera: None. X.M. Shao: None. T.C. Friedman: Advisory Panel; Ended; Acella Pharmaceuticals. J. Espinoza-Derout: None.
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.
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