Recurrent Ethanol Treatment does not Produce a Cumulative Effect on Plasma Leptin Levels in Rats
Authors: Narez Arline , Ahmed Mahad , Fuentes Victoria , McDougal David 
Published: May 2024

Background: Hypoleptinemia is a potent orexigenic signal. Chronic ethanol (EtOH) consumption is associated with weight gain in humans, and acute ethanol treatment leads to reductions in leptin concentrations in both fasted humans and rats. The objective of this study was to determine whether short-term recurrent ethanol treatment has a cumulative effect on plasma leptin levels in rats, and whether treatment in the fed or fasted state influences the leptin lowering effect of EtOH. We hypothesized that recurrent EtOH treatment would have a cumulative effect on leptin levels, and that these effects would be more pronounced in the fed state, when leptin levels are highest. Methods: Two separate groups of male Sprague Dawley rats were exposed to either oral or intravenous (IV) treatment with EtOH (2g/kg via oral gavage or 0.067 g/kg/min IV for 30 min; n=7/group) on three consecutive days. Each rat served as its own control and received saline treatment either 7 d prior to or 7 d following exposure to EtOH. The oral group was fasted 12-14 h (overnight) prior to treatment, while the IV group was not fasted. Plasma leptin and EtOH levels were measured each day at baseline and 3 h following EtOH treatment. Data are expressed as mean ± SEM. A two-way repeated measures ANOVA was used to test for differences in plasma leptin and EtOH levels due to treatment (saline vs. EtOH) or day (cumulative effect of treatment). Results: Post-treatment ethanol levels in the oral and IV groups (55 ± 6.9 and 45 ± 6.3 mM, respectively) were higher than saline-treated rats (p>0.001). Baseline leptin levels in the oral treatment (fasted) group were 3.4 ± 0.3 and 3.9 ± 0.2 ng/mL under saline and leptin treated conditions, respectively. There was a significant main effect of treatment but not of day in the oral group (p=0.04 and p=0.38, respectively). In the oral group, average daily change in leptin levels 3 h post treatment in saline and leptin treated rats were -0.18 ± 0.05 and -0.72 ± 0.1 ng/mL, respectively. Baseline leptin levels in the IV group (fed) were 7.8 ± 0.3 and 6.7 ± 0.1 ng/mL, in saline and leptin treated rats respectively. There was no significant main effect of treatment or day in the IV group (p=0.17 and p=0.41, respectively). In the IV group, average daily changes in leptin levels 3 h following treatment in saline and leptin treated rats were -1.7 ± 0.2 and -1.3 ± 0.3 ng/mL, respectively. Conclusion: Although we were able to replicate previous work indicating reduced leptin levels following acute EtOH treatment in fasted rats, our results do not support a cumulative leptin-lowering effect of recurrent EtOH treatment. Furthermore, IV EtOH treatment in the fed state did not have any impact on leptin levels. This suggests that the leptin-lowering effects of EtOH may either require the fasted state or may require ingestion and exposure of the GI system to EtOH. NIH R01 DK131165-01A1. 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.