(LB04-02-25) An Olive-Derived Small Molecule Ameliorates Metabolic Abnormalities in Diet-Induced Obesity by Modulating Food Intake

Objectives: Therapeutic strategies aimed at weight reduction are essential for managing obesity-related metabolic disorders such as type 2 diabetes (T2D). We recently found that elenolic acid (EA), a bioactive small molecule, improves blood glucose control, induces weight loss, and decreases food intake in diet-induced obese (DIO) mice. These beneficial effects were associated with elevated levels of gut-derived metabolic hormones. In this study, we further investigated whether the metabolic improvements induced by EA are primarily mediated by reduced food intake.

Methods: DIO mice were treated with either EA (50 mg/kg) or vehicle for 21 days. To isolate effects independent of food consumption, EA-treated mice were pair-fed with obese control mice to equalize daily energy intake. Metabolic parameters including body weight and food intake were recorded daily. At the beginning and end of the experiment, fasting and non-fasting blood glucose levels and body composition were measured, and at the end of the study, fecal lipid content, liver weight, hepatic triglyceride content, fasting plasma insulin and leptin levels, and HOMA-IR were measured.

Results: After 21 days of treatment, EA-treated mice exhibited similar reductions in both average daily food intake and cumulative food intake compared to their pair-fed counterparts, with both groups significantly lower than the obese control group. Correspondingly, EA-treated and pair-fed mice displayed comparable body weight loss, significantly greater than in the obese control mice. No significant differences in body composition among groups were detected. Fasting and non-fasting blood glucose, liver weight, fasting insulin, leptin levels, and HOMA-IR scores were comparable between EA-treated and pair-fed groups, and both were significantly improved compared to obese control mice.

Conclusions: Our findings indicate that the beneficial metabolic effects of EA in DIO mice are largely dependent on reduced food intake. These results enhance our understanding of EA’s therapeutic potential in addressing obesity and its associated metabolic disturbances.

Funding Sources: The work was supported by National Institutes of Health (R01DK134401-01A1), Diabetes Action Research and Education Foundation, and SJ Ritchey Research Grants (to D. Liu).