Fisetin effects on lean mass in exercising vs sedentary mice

When an individual attempts to lose weight by dieting and exercise, lean mass, including muscle, is often lost in the process. Fisetin (a flavonoid found naturally in many fruits and vegetables) may influence lean mass due to its ability to improve function of muscle progenitor cells. Exercise is known to help preserve lean mass but it is unknown whether the influence of fisetin on lean mass occurs when mice are not exercising. The purpose of this study was to examine the ability of fisetin to preserve lean mass in adult mice with or without access to a running wheel. We hypothesized that fisetin will preserve lean mass in adult, exercising mice. Methods: Exercising adult male and female C57BL/6 mice (n = 4 per group) had unlimited access to a running wheel while sedentary mice had a locked running wheel in their cage. Mice were fed ad libitum standard lab chow or lab chow containing 500ppm fisetin for four weeks. During the treatment period, body weight, food intake, physical activity and energy expenditure were measured using indirect calorimetry chambers (Sable Systems, Las Vegas, NV). Body composition measurement was performed at the beginning and end of the four-week experimental period using NMR (EchoMRI, Houston, TX). Neither fisetin nor wheel running altered food intake over the course of the study. Fisetin significantly reduced fat mass (26.4 +/- 8.4%, p = 0.0425) in male mice with no effect on lean mass. This was independent of access to a running wheel. Over the four-week period, female mice given standard lab chow increased fat mass by 34.9 +/- 16.3% and this increase was prevented by fisetin. Sedentary females given standard lab chow had an increase in lean mass (p = 0.038), which was further increased by the presence of a running wheel (p = 0.0178). Interestingly, females given fisetin chow exhibited a 2.3 +/- 0.7 fold increase (p = 0.0646) in wheel running during the dark period as compared to females given standard lab chow. These data suggest that fisetin has beneficial but differential effects on lean and fat mass in males and females. This work was funded by the funded by the following grants: NIH R01DK134468, VA BLRD I01RX003901 and VA RRD I01RX003901. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.