What does this research mean for the field?

Inhibiting lipolysis with acipimox normalizes proinflammatory serum lipidomic dysregulation and mitigates cardiometabolic complications induced by electronic cigarettes in a diet-induced obesity mouse model. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.ESTABLISHES_NEW_DIRECTION.

What question did this study set out to answer?

This research aims to investigate the metabolic effects of electronic cigarettes and the potential of acipimox to normalize lipid dysregulation in a mouse model of diet-induced obesity.

June 7, 2026

3063-LB: Acipimox Normalizes Proinflammatory Serum Lipidomic Dysregulation Produced by Electronic Cigarette in a Diet-Induced Obesity Mouse Model

Key Points

This research aims to investigate the metabolic effects of electronic cigarettes and the potential of acipimox to normalize lipid dysregulation in a mouse model of diet-induced obesity.
C57BL/6J mice on a high-fat diet were treated with saline, e-cig (2.4% nicotine), or e-cig (2.4%)+acipimox for 12 weeks.
Serum samples were analyzed using equiSPLASH lipidomics and LC-MS/MS, with data processed through PCA and lipid pathway enrichment analysis.
Differential lipid analysis identified altered lipid profiles and inflammatory markers associated with treatment.
PCA revealed distinct lipid profiles between e-cig and saline groups, with e-cig+ACIP overlapping with saline, indicating normalization.
149 altered lipids were detected, with significant enrichment of ether-linked triacylglycerols and lysophosphatidylcholines under e-cig treatment.
Acipimox restored key enzymatic activities impacted by e-cig exposure, mitigating inflammation and oxidative stress.

Abstract

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. Disclosure 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. 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.

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3063-LB: Acipimox Normalizes Proinflammatory Serum Lipidomic Dysregulation Produced by Electronic Cigarette in a Diet-Induced Obesity Mouse Model

Key Points

Abstract

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