Obesity without Muscle Insulin Resistance in High-Starch Diet Mice — ASN Events

Obesity without Muscle Insulin Resistance in High-Starch Diet Mice (#64)

Amanda E Brandon 1 2 , Lewin Small 1 , Tuong-Vi Nguyen 1 , Eurwin Suryana 1 , Gregory J Cooney 1 2
  1. Garvan Institute of Medical Research, Sydney, NSW, Australia
  2. The University of Sydney, University Of Sydney, NSW, Australia

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 (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 (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.

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