Background/aims

Non-alcoholic steatohepatitis is an important disease whose pathophysiology remains incompletely understood, although in humans a strong association with insulin resistance exists. Mice fed a methionine-choline deficient (MCD) diet develop steatohepatitis, however the influence of insulin in this model is unknown.

Methods

Male FVB/NJ mice were fed the MCD, MCD control or chow diet for 10 or 28 days. Fasting glucose, ALT, triglyceride and insulin was measured. Glucose tolerance tests (GTT) and insulin tolerance tests (ITT) were performed followed by quantitative insulin sensitivity check index (QUICKI) determination.

Results

ALT levels were significantly higher in the MCD group. Fasting glucose was 81+/-5 mg/dl in MCD diet fed mice, compared to MCD controls (196+/-46 mg/dl) and chow (199+/-15 mg/dl) (P<0.0001). During GTT and ITT, the effect of glucose administration on blood glucose was dampened, and the insulin effect more pronounced in the MCD group (P=0.026 and P<0.001). QUICKI in MCD fed mice was significantly higher than in the chow fed mice.

Conclusions

GTT, ITT and QUICKI confirmed the absence of insulin resistance in the MCD fed mice. This model causes fibrosing steatohepatitis and may help delineate the non-insulin resistant mechanisms involved in human steatohepatitis.