A high fat diet in mice leads to the accumulation of fat in adipose tissue (WAT) and non-adipose tissues and is linked to the development of glucose intolerance and insulin resistance. A diet high in starch can also lead to the accrual of WAT but the impact on glucose metabolism is less clear. We housed 3 groups of mice for 30 weeks at thermoneutrality (29oC) and fed animals a standard chow (20% protein, 11% fat, 69% carbohydrate), a high starch (Hi-ST; 20% protein, 20% fat, 60% starch) or a high fat diet (Hi-F; 20% protein, 60% lard, 20% starch). Body weight, food intake, body composition (DEXA), and glucose tolerance were assessed and tissues sampled for analysis at the end of the feeding period.
Both Hi-ST and Hi-F diet mice gained significantly more body weight than chow-fed mice (42.8±1.5g; 38.4±1.7g; 29.8±0.6g, respectively) and had significantly more fat mass by DEXA scanning (8.5±0.7g; 8.5±0.7g; 4.4±0.2g, respectively). Despite a similar degree of fatness, Hi-ST mice had better glucose tolerance than Hi-F mice after an ipGTT (iAUC 535±56 vs 888±59; P<0.001) and were similar to lean, chow-fed mice (iAUC 528±53). Interestingly, both Hi-ST and Hi-F mice had increased levels of triglycerides in liver compared to chow-fed mice (Hi-ST 20.3±0.9µmol/g; Hi-F 23.6±1.9µmol/g; chow 10.3±0.9µmol/g). Immunoblotting showed decreases in fatty acid synthase (FAS) and acetyl CoA carboxylase (ACC) protein in WAT and steroyl CoA desaturase (SCD1) and ACC in the liver of Hi-F mice but expression of these enzymes was largely maintained in Hi-ST mice. These results indicate that mice become obese on a Hi-ST diet but do not develop glucose intolerance, as do similarly obese mice fed a Hi-F diet. These models may be useful for determining mechanistic links between obesity and reduced insulin action.