Abstract
The prevalence of non-alcoholic fatty liver disease (NAFLD), which is developed from hepatic steatosis, is increasing worldwide. However, no specific drugs for NAFLD have been approved yet. To observe the effects of Rho, a fraction from Rhodiola crenulate, on non-alcoholic hepatic steatosis, three mouse models with characteristics of NAFLD were used including high-fat diet (HFD)-induced obesity (DIO) mice, KKAy mice, and HFD combined with tetracycline stimulated Model-T mice. Hepatic lipid accumulation was determined via histopathological analysis and/or hepatic TG determination. The responses to insulin were evaluated by insulin tolerance test (ITT), glucose tolerance test (GTT), and hyperinsulinemic-euglycemic clamp, respectively. The pathways involved in hepatic lipid metabolism were observed via western-blot. Furthermore, the liver microcirculation was observed by inverted microscopy. The HPLC analysis indicated that the main components of Rho were flavan polymers. The results of histopathological analysis showed that Rho could ameliorate hepatic steatosis in DIO, KKAy, and Model-T hepatic steatosis mouse models, respectively. After Rho treatment in DIO mice, insulin resistance was improved with increasing glucose infusion rate (GIR) in hyperinsulinemic-euglycemic clamp, and decreasing areas under the blood glucose-time curve (AUC) in both ITT and GTT; the pathways involved in fatty acid uptake and de novo lipogenesis were both down-regulated, respectively. However, the pathways involved in beta-oxidation and VLDL-export on hepatic steatosis were not changed significantly. The liver microcirculation disturbances were also improved by Rho in DIO mice. These results suggest that Rho is a lead nature product for hepatic steatosis treatment. The mechanism is related to enhancing insulin sensitivity, suppressing fatty acid uptake and inhibiting de novo lipogenesis in liver.
Highlights
Non-alcoholic fatty liver disease (NAFLD), a spectrum of liver disease developing progressively from simple steatosis to steatohepatitis, fibrosis, and cirrhosis, is increasing worldwide with the incidence of 20–30% in Western countries and 5–18% in Asia (Sayiner et al, 2016) and is caused by a multitude of factors including the insulin resistance (Bugianesi et al, 2010; Petta et al, 2016)
The hepatic steatosis was significantly improved by Rhodiola crenulata (Rho) treatment with 35.5% reduction in lipid accumulation compared with diet (HFD)-induced obesity (DIO) mice (Figures 2A,D)
David Vauzour et al indicated that n-3 Fatty acids combined with flavan-3-ols (FLAV) prevent steatosis and liver injury in a murine model by regulating the expression of genes involved in hepatic lipid accumulation, such as PPARα (Vauzour et al, 2018)
Summary
Non-alcoholic fatty liver disease (NAFLD), a spectrum of liver disease developing progressively from simple steatosis to steatohepatitis, fibrosis, and cirrhosis, is increasing worldwide with the incidence of 20–30% in Western countries and 5–18% in Asia (Sayiner et al, 2016) and is caused by a multitude of factors including the insulin resistance (Bugianesi et al, 2010; Petta et al, 2016). The auxo-action of insulin resistance in hepatic steatosis/NASH is induced by enhancing de novo lipogenesis in liver and subsequent lipolysis in adipose tissue. Insulin resistance plays a key role in the progression of NAFLD and maybe a therapeutic target for its treatment. We identified Rho, the active fractions from Rhodiola crenulate, as an effective nature product for NAFLD treatment. Its mechanism, including the insulin sensitizing effect and the pathways involved in hepatic lipid metabolism, was investigated in DIO mice
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
