The lipolysis inhibitor acipimox reverses the cardiac phenotype induced by electronic cigarettes

The lipolysis inhibitor acipimox reverses the cardiac phenotype induced by electronic cigarettes

Electronic cigarettes (e-cigarettes) are a prevalent alternative to conventional nicotine cigarettes among smokers and people who have never smoked. Increased concentrations of serum free fatty acids (FFAs) are crucial in generating lipotoxicity. We studied the effects of acipimox, an antilipolytic...

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Bibliographic Details
Published in:Scientific reports Vol. 13; no. 1; pp. 18239 - 15
Main Authors: Espinoza-Derout, Jorge, Arambulo, Jose Mari Luis, Ramirez-Trillo, William, Rivera, Juan Carlos, Hasan, Kamrul M., Lao, Candice J., Jordan, Maria C., Shao, Xuesi M., Roos, Kenneth P., Sinha-Hikim, Amiya P., Friedman, Theodore C.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 25-10-2023
Nature Publishing Group
Nature Portfolio
Subjects:
4-Hydroxynonenal
631/45
631/80
692/4019
692/4019/592
Animals
Apyrimidinic sites
Cigarettes
Cytokines
Deoxyribonucleic acid
DNA
DNA damage
Electronic cigarettes
Electronic Nicotine Delivery Systems
Fatty acids
Gene expression
Gene set enrichment analysis
Heme oxygenase (decyclizing)
High fat diet
Humanities and Social Sciences
Humans
Inflammation
Lipolysis
Localization
Mice
Mice, Inbred C57BL
multidisciplinary
Nicotine
Oxidative stress
p53 Protein
Phenotype
Phenotypes
Science
Science (multidisciplinary)
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Summary:Electronic cigarettes (e-cigarettes) are a prevalent alternative to conventional nicotine cigarettes among smokers and people who have never smoked. Increased concentrations of serum free fatty acids (FFAs) are crucial in generating lipotoxicity. We studied the effects of acipimox, an antilipolytic drug, on e-cigarette-induced cardiac dysfunction. C57BL/6J wild-type mice on high fat diet were treated with saline, e-cigarette with 2.4% nicotine [e-cigarette (2.4%)], and e-cigarette (2.4%) plus acipimox for 12 weeks. Fractional shortening and ejection fraction were diminished in mice exposed to e-cigarettes (2.4%) compared with saline and acipimox-treated mice. Mice exposed to e-cigarette (2.4%) had increased circulating levels of inflammatory cytokines and FFAs, which were diminished by acipimox. Gene Set Enrichment Analysis revealed that e-cigarette (2.4%)-treated mice had gene expression changes in the G2/M DNA damage checkpoint pathway that was normalized by acipimox. Accordingly, we showed that acipimox suppressed the nuclear localization of phospho-p53 induced by e-cigarette (2.4%). Additionally, e-cigarette (2.4%) increased the apurinic/apyrimidinic sites, a marker of oxidative DNA damage which was normalized by acipimox. Mice exposed to e-cigarette (2.4%) had increased cardiac Heme oxygenase 1 protein levels and 4-hydroxynonenal (4-HNE). These markers of oxidative stress were decreased by acipimox. Therefore, inhibiting lipolysis with acipimox normalizes the physiological changes induced by e-cigarettes and the associated increase in inflammatory cytokines, oxidative stress, and DNA damage.
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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-023-44082-x