SAT-689 Metabolic Effects of Self-inhaled Nicotine in Adolescent Mice

Abstract Disclosure: X. Xu: None. Y. Shi: None. H. Liu: None. Y. Xu: None. Background: Most previous animal studies on nicotine have employed passive injection methods, which do not accurately replicate human smoking behavior. Additionally, while the metabolic effects of nicotine have been extensively studied in adult humans, there is a notable lack of research focused on adolescents. This study aims to address this gap in knowledge. Objective: To utilize a novel smoking box designed to simulate human smoking behavior in mice and evaluate the metabolic effects of self-inhaled nicotine during adolescence. Methods: The smoking box consists of two interconnected chambers equipped with motion sensors. These sensors detect the presence of mice in either chamber, triggering electronic switches to vaporize and deliver smoke containing the substance of choice through a vent. Mice were divided into two groups: a “Control-Control” group, where both chambers vaporized oil (commercial juice without flavor), and a “Nicotine-Control” group, where one chamber vaporized oil with 12 mg/ml nicotine, while the other vaporized oil. 56 mice (5-8 weeks old; 30 male, 26 female) were exposed to the smoking box for 30 minutes daily over 10 consecutive days. Food intake, body weight, body fat mass, lean mass, post-exposure intraperitoneal glucose tolerance test (IGTT), and cortisol levels were measured. Results: During the exposure period, no significant differences in food intake or body weight were observed between the two groups. Post-exposure assessments also revealed no differences in IGTT or cortisol levels. However, male mice in the Nicotine-Control group exhibited significantly greater weight gain (4.8 ± 1.3 g vs. 3.5 ± 0.9 g, P= 0.03) and fat mass gain (from 1.7 ± 0.3 g to 3.9 ± 1.9 g, P =0.01 vs. from 1.9 ± 0.5 g to 2.9 ± 1.7 g, P=0.12) following cessation of exposure compared to the Control-Control group. These effects were not observed in female mice. Conclusions: Self-inhaled nicotine exposure in adolescent mice does not provide any metabolic benefit. Instead, it is associated with increased weight gain, particularly in fat mass, following cessation. Additionally, nicotine exposure does not alter stress hormone levels. These findings challenge the common belief among adolescents that smoking helps with weight control or stress relief, underscoring the need for further education on the metabolic risks of nicotine use. Presentation: Saturday, July 12, 2025