Thiazolidinedione induces a therapeutic effect on hepatosteatosis by regulating stearoyl-CoA desaturase-1, lipase activity, leptin and resistin

Hepatosteatosis is a disease present worldwide, which presents a number of health problems. Recently, thiazolidinedione (TZD) has been used as a therapy for lipid disorders. The present study demonstrates the potential of TZD as a treatment for hepatosteatosis and its mechanism of action, particularly focusing on its role in lipid metabolism. A total of 60 (80–90 g) rats were divided into three groups: A normal group with a standard diet, a high-fat, high-carbohydrate diet (HFCD) group or a HFCD+TZD group (n=20/group). The HFCD induced hepatosteatosis over a period of 12 weeks and the HFCD+TZD group were administered TZD in weeks 13–16. Blood and tissue samples were collected to measure hepatic function, the lipid profile, metabolism and hormone biomarkers, including serum triglyceride (TG), lipoprotein lipase (LPL), stearoyl-CoA desaturase (SCD-1), leptin and resistin. The HFCD-fed rats exhibited a significant increase in serum TG, total cholesterol, low-density lipoproteins, alanine transaminase and bilirubin compared with the normal group as well as a significant decrease in high-density lipoprotein. In addition, serum leptin and resistin were significantly elevated in the HFCD group compared with the normal group. The administration of TZD significantly increased SCD-1 activity and significantly inhibited LPL activity. It also attenuated the changes in the lipid profiles and normalized serum leptin and resistin levels. The results of the present study indicated that HFCD induced lipid abnormalities associated with hypertriglyceridemia, hypercholesterolemia and hepatosteatosis. These changes resulted from disruption to leptin and resistin, which may be due to alterations in LPL and SCD-1 activity. TZD mitigated the effects of HFCD-induced hepatosteatosis, indicating a possible regulatory effect of TZD in the development of hepatosteatosis. The authors suggest that the manipulation of SCD-1 and lipase by TZD may be useful as a treatment for hepatosteatosis.