Mice fed a high-fat diet accumulate lipid in adipose tissue (WAT) and non-adipose tissues and develop glucose intolerance and insulin resistance. A diet high in starch can also lead to significant fat deposition but the impact on glucose metabolism is less defined.

Three groups of mice were housed at thermoneutrality (29^oC) and fed a chow (20% protein, 11% fat, 69% crude carbohydrate), high starch (Hi-ST; 20% protein, 20% fat, 60% corn starch) or high fat diet (Hi-F; 20% protein, 60% lard, 20% corn starch). Body weight, body composition (DEXA), adipocyte size and glucose tolerance (oGTT) were monitored and after 25-30 weeks of diet mice from each group underwent a hyperinsulinaemic-euglycaemic clamp with tracers to determine whole body and tissue specific glucose metabolism.

Both Hi-ST and Hi-F diet mice acquired significantly more fat than chow-fed mice. Hi-ST and Hi-F mice had larger adipocytes in both the epididymal and subcutaneous WAT compared to chow mice (mean adipocyte area, p<0.05). Despite similar fatness and adipocyte size, Hi-ST mice had better oGTT than Hi-F mice (iAUC 364±36 vs 657±69; P<0.001) and were similar to lean, chow-fed mice (iAUC 359±20). During the clamp, Hi-ST mice exhibited intermediate whole body insulin sensitivity between the more sensitive chow mice and more resistant Hi-F mice (Chow 30.1±2.1; Hi-St 19.6±1.9; Hi-F 11.1±1.4 mg/kg/min p<0.05). Hi-ST and Hi-F mice both had liver insulin resistance (reduced insulin suppression of HGO) but Hi-ST mice did not exhibit any reduction in skeletal muscle glucose uptake (chow 22.1±1.8; Hi-ST 21.0±2.3; Hi-F 14.0±2.5 µmol/100g/min).

These results indicate that despite development of significant obesity, mice fed a Hi-ST diet display a different pattern of glucose tolerance and insulin sensitivity to similarly obese mice fed a Hi-F diet. The Hi-ST model offers new opportunities for investigating mechanistic links between obesity and reduced insulin action.