Inhibition of Fat Accumulation by Hesperidin in Caenorhabditis elegans

Hesperidin, abundant in citrus fruits, has a wide range of pharmacological effects including anticarcinogenic, anti-inflammatory, antioxidative, radioprotective and antiviral activities. However, relatively few studies on the effects of hesperidin on lipid metabolism have been reported. Here, using Caenorhaditis elegans as a model animal, we found that 100 µM hesperidin significantly decreased fat accumulation both in high fat worms cultured in nematode growth medium containing 10 mM glucose (83.5%±1.2 vs control by Sudan black B staining and 87.6%±2.0 vs control by Oil Red O staining, P<0.001) and daf-2 mutant worms (87.8%±1.4 vs control by Oil Red O staining, P<0.001). Furthermore, 50 µM hesperidin decreased the ratio of oleic acid to stearic acid (C18:1Δ9/C18:0) (P<0.05), and supplementation of oleic acid could restore the inhibitory effect of hesperidin on fat accumulation. Hesperidin significantly downregulated the expression of stearoyl-CoA desaturase, fat-6 and fat-7 (P<0.05), and mutation of fat-6 and fat-7 reversed fat accumulation inhibited by hesperidin. In addition, hesperidin decreased the expression of other genes involved in lipid metabolism, including pod-2, mdt-15, acs-2 and kat-1 (P<0.05). These results suggested that hesperidin reduced fat accumulation by affecting several lipid metabolism pathways, such as fat-6 and fat-7. This study provided new insights into elucidating the mechanism underlying the regulation of lipid metabolism by hesperidin.