Effects of diosmin and diosmetin on weight gain and fat accumulation in mice fed a HFHS diet. (a) Body weight was higher in mice fed a HFHS diet than in mice fed ND, and supplementation with 0.5% diosmin and 0.5% diosmetin decreased the body weight of HFHS‐fed mice. However, a significant difference between the HFHS diet and HFHS diet with diosmin groups was seen. (b) Food intake was not significantly different between the mice fed a HFHS diet and those on a HFHS diet supplemented with diosmin or diosmetin, except during the first week. (c) Liver weight increased in mice fed a HFHS diet compared with the ND group, but significantly decreased in mice fed a HFHS diet supplemented with diosmin or diosmetin. (d) Epididymal fat weight was significantly higher in HFHS‐treated mice. Diosmin supplementation significantly reduced the epididymal fat accumulation induced by a HFHS diet. Diosmetin treatment did not affect the epididymal fat weight. (e) The retroperitoneal fat weight was significantly higher in HFHS‐treated mice. In addition, both diosmin and diosmetin significantly reduced the retroperitoneal fat content induced by a HFHS diet. (f) Greater fat accumulation in liver, epididymal, and retroperitoneal tissues was observed in HFHS‐fed mice based on visual observation. However, this effect was attenuated by diosmin and diosmetin supplementation. (g) Histological examination of liver and epididymal fat tissues after H&E staining showed that the HFHS diet led to an increase in fat accumulation, which was subsequently reduced by decreasing the size of the lipid droplets in those tissues when the diet was supplemented with diosmin or diosmetin. Values are presented as mean ± SE based on ANOVA (n = 10 mice per group). The different lowercase letters indicate significant differences among all groups, and the superscript (*) indicates significant differences between the HFHS group and both the diosmin and diosmetin groups, p < .05