Mice fed a high-fat diet accumulate lipid in adipose 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 (29oC) 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 (EchoMRI), glucose tolerance (oGTT) were monitored and after 20-25 weeks of diet mice from each group underwent a hyperinsulinaemic-euglycaemic clamp with tracers to determine whole body and tissue specific glucose metabolism. In a separate cohort, mice were fed for 4 weeks and injected with 3H-H2O to measure de novo lipogenesis (DNL).
Both Hi-ST and Hi-F diet mice acquired significantly more fat than chow-fed mice. Despite similar adiposity, Hi-ST mice had better oGTT than Hi-F mice and were similar to chow mice (p<0.05). During the clamp, Hi-ST mice had similar glucose infusion rates (GIR) to chows while Hi-F mice were insulin resistant (decreased GIR; Chow 36.4±2.7; Hi-St 30.7±2.8; Hi-F 21.1±1.9 mg/kg lean mass/min p<0.05). Hi-ST had better suppression of HGO than Hi-F mice and Hi-ST mice did not exhibit any reduction in skeletal muscle glucose uptake (chow 25.8±3.4; Hi-ST 18.6±1.6; Hi-F 13.9±1.3 µmol/100g/min). Liver DNL was increased in the Hi-ST group while the Hi-F mice DNL was suppressed (chow 20.5±1.4; Hi-ST 35.7±3.8; Hi-F 14.5±1.1 μmol 3H20/h).
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.