(P26-040-25) Effects of Fisetin on Lipid Metabolism in Caenorhabditis elegans

Objectives: Fisetin (3,3',4',7-tetrahydroxyflavone) is a yellow-pigmented flavanol found in strawberries, cucumbers, peaches, and honey locusts. Fisetin has been reported to have anti-cancer, anti-aging, and anti-inflammatory properties, and there was limited evidence that fisetin has anti-obesity effects. Thus, this study aimed to determine if fisetin reduces fat accumulation using Caenorhabditis elegans as an in vivo model. C. elegans is an invertebrate animal model commonly used in life science research, including the study of lipid metabolism, due to its ease of maintenance, rapid lifecycle, and highly conserved genes and pathways with mammals.

Methods: On the first day of adulthood, C. elegans were treated with fisetin at 100 μM and 200 μM for 48 hours in wild-type or other mutants. Fat accumulation was determined by quantifying the total triglyceride normalized by the protein. The pharyngeal pumping rates and locomotive activities were determined during treatment. Gene expressions were determined by RT-PCR.

Results: Fisetin treatment at 100 μM and 200 μM significantly reduced total triglyceride levels compared to the control in wild-type C. elegans by 22% and 39%, respectively. Fisetin did not affect pharyngeal pumping rates, which indicates that it did not affect food intake. At the same time, fisetin treatment significantly increased locomotive activity, which implies that fisetin treatment promoted energy expenditure. Effects of fisetin were further tested in various mutants and genes involved in lipid metabolism. Fisetin treatment did not influence lipogenesis or lipid oxidation but reduced fat accumulation via increased energy expenditure independent of AMP-activated protein kinase (AMPK) or insulin/insulin-like growth factor signaling pathway.

Conclusions: These results suggest that fisetin reduces fat accumulation via increased energy expenditure in C. elegans.

Funding Sources: This project was in part supported by the National Institute of Food and Agriculture, the U.S. Department of Agriculture, the Center for Agriculture, Food and the Environment.