As the lipid lowering agent fenofibrate (FF) may protect against some diabetes related complications, we examined whether FF prevents NASH in an established rodent model induced by high fat feeding and diabetes.

Wild type C57BL/6 male mice (n=80) were fed a high fat diet (HFD: 45%kCal fat) or standard laboratory chow (CHOW: 12%kCal fat) ad libitum, for 15 weeks, when after randomisation some animals were made diabetic (HFD+DM or CHOW+DM) with mini-dose STZ. Some animals were treated with fenofibrate (100mg/kg in food) from the time of diabetes induction, and blood glucose levels (BGLs) were monitored and insulin tolerance tests (ITTs) performed. Mice were terminated 10 weeks after diabetes onset, and livers were examined for lipid, macrophage counts and histology.

Table data are mean±SD, *P<0.05 vs CHOW. #P<0.05 vs same group without FF

FF improved BGLs in diabetic animals fed CHOW or HFD (table). In contrast, each diabetic group treated with FF had greater insulin resistance at ITT compared with the respective diabetic group not treated with FF. Termination body weight was reduced by FF in the HFD group. FF did not prevent induction of liver lipid by Oil-Red O measures nor inflammation by liver macrophage counts. The liver profibrotic protein connective tissue growth factor (CTGF) at immunohistochemistry was also not improved by FF treatment and hepatocyte ballooning was exacerbated in HFD+DM+FF, compared with HFD+DM (not shown). This data indicates that even though fenofibrate has desirable effects on blood glucose, it does not protect against NASH. Supported by NHMRC Project Grant #632822.