Early hepatic fat content as a predictor for later development of type 2 diabetes

Aims: New Zealand Obese (NZO) mice are an established model of the metabolic syndrome and sexually dimorphic susceptibility to type 2 diabetes. Males develop hyperglycemia that turns into diabetes even on standard diet, while females are protected unless they are fed with high-fat diet that contains 60 energy per cent from fat. The aim of this study was to examine the influence of fat distribution on onset and development of type 2 diabetes in female NZO mice.

Methods: Female NZO mice were kept on SD (9% fat) and HFD (60% fat) for 24 weeks. Body fat distribution and liver fat content were determined by computed tomography at week 10, 16 and 22. Oral glucose tolerance tests were conducted at week 6 and 11, and body weight and blood glucose levels were assessed weekly.

Results: Under these HFD conditions 67% of mice developed hyperglycemia, but one third of them were able to compensate and reach normal blood glucose values after transient hyperglycemia. All animals on SD and 33% of animals on HFD were normoglycemic through the entire experiment. Fat distribution in abdominal region was independent of diabetes status but liver fat content correlated with blood glucose values. Furthermore, early intrahepatic fat accumulation at week 10 together with blood glucose level at week 9 were shown to be predictors for later onset of diabetes.

Conclusion: In the NZO mouse the early increase in liver fat and blood glucose but not the early fat distribution predict for later onset of type 2 diabetes. Fat enriched diets counteract the protective action of estrogens against diabetes in some females indicating that a high lipid load either supresses estrogen levels or estrogen activity.