Electronic cigarette-induced adipose tissue inflammation is rescued by acipimox

Abstract

Objective: Electronic cigarettes (e-cigarettes) are the most commonly used tobacco product in the U.S. with high frequency among youth. Our laboratory has shown that e-cigarettes induce metabolic changes and cardiac dysfunction associated with elevated serum free fatty acids (FFAs). Adipose tissue dysfunction is a proinflammatory state that mediates multiple pathogenic mechanisms in the well-known associations between cardiovascular pathology, hypertension, and metabolic syndrome. In adipose tissue, crown-like structures (CLSs) are signs of metabolic dysfunction and adipose tissue inflammation. CLSs are composed of macrophages surrounding dead or dying adipocytes. Hypothesis: We hypothesize that e-cigarettes produce inflammation in adipose tissue, which is mediated by lipolysis. Methods: C57BL/6J wild-type mice on high fat diet were treated with saline aerosol, e-cigarette with 2.4% nicotine [e-cig (2.4%)], and e-cig (2.4%) plus acipimox (an inhibitor of lipolysis) [e-cig (2.4%)+ACIP], for 12 weeks. Adipose tissue was stained with Hematoxylin and Eosin (H&E). CD45 is the surface marker of immune cells. Therefore, we quantified the number of CD45+ cells in adipose tissue. Additionally, we performed a transcriptomic evaluation with Gene Set Enrichment Analysis (GSEA). Results: H&E staining showed abundant CLSs in mice exposed to e-cigarettes in adipose tissue. The number of CLSs was normalized in the e-cig (2.4%)+ACIP group. E-cigarettes induced an increase of CD45+ cells in adipose tissue, which was also normalized by acipimox. GSEA of the RNA-seq data revealed upregulation of inflammatory pathways in adipose tissue from e-cigarette-treated mice, including Interferon-g and Interferon-a response, which were rescued by acipimox treatment. Summary: Inhibiting lipolysis with acipimox normalizes the inflammatory changes induced by e-cigarettes in adipose tissue. These findings suggest a functional interplay between adipose tissue and metabolic dysfunction caused by e-cigarettes. Funding: JE-D work was supported by the NIH grants: NIGMS (SC2GM135127), NIMHD (S21MD000103), the CDU Accelerating Excellence in Translational Science (AXIS) (U54MD007598-14S2), and a voucher from UCLA CTSI (UL1TR001881). TCF was supported by the California TRDRP grant (28CP-0040), DODCDMRP grant (PR190942), and NIDA (R25DA050723) grants. XMS was supported by a NIDA (R42DA044788) grant. KPR was supported DODCDMRP grant (PR190942-P1). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.