Ginsenoside Rg3 attenuates fat accumulation in zebrafish with high-fat-diet-induced obesity

Ginsenoside Rg3 is one of major steroidal saponins in Panax ginseng that has demonstrated several therapeutic effects. In this study, we investigated the effects of ginsenoside Rg3 on lipid accumulation in a high-fat diet (HFD) larval zebrafish model by analyzing fluorescence intensity, total cholesterol (TC), and triglyceride (TG) levels. The effects of ginsenoside Rg3 in a HFD adult zebrafish model were also evaluated on the basis of body length, body weight, body mass index (BMI), hematoxylin–eosin (HE) staining, Oil red staining, quantitative PCR, TC, and TG. In addition, the intestinal bacteria in zebrafish that were capable of metabolizing ginsenoside Rg3 into ginsenoside deglycosylase ginsenoside Rh2 and aglycon ginsenoside deglycosylated protopanaxadiol were measured. Results demonstrated that the fluorescence density of the local trunk in the HFD larval zebrafish model under ginsenoside Rg3 treatment had reduced compared with high cholesterol (HC) group. Moreover, TC levels were significantly lower in the Rg3 treatment group than in the HC group ( P < 0.01). However, TG levels did not significantly differ between groups ( P > 0.01). In addition, Rg3 could improve the related effects caused by HFD and caused zebrafish body length, body weight, and BMI to approach normal levels. HE and Oil Red O staining of liver revealed the marked accumulation of lipid droplets and histopathological changes in hepatocytes. These changes were attenuated by Rg3 treatment. Rg3 induced the expression of lipid-catabolism-associated and anabolism-associated genes, and the possible mechanism could be attributed to the down-regulation of cholesterol synthesis and up-regulation of cholesterol transport. These results reflected the influence of Rg3 on lipid metabolism and indicated that ginsenoside Rg3 could attenuate fat accumulation and might be a potential agent for preventing obesity.