Improved glucose tolerance in acyl CoA:diacylglycerol acyltransferase 1-null mice is dependent on diet

BACKGROUND: Mice that lack acyl CoA:diacylglycerol acyltransferase (Dgat1(-/- )mice) are reported to have a reduced body fat content and improved glucose tolerance and insulin sensitivity. Studies so far have focussed on male null mice fed a high fat diet and there are few data on heterozygotes. We compared male and female Dgat1(-/-), Dgat1(+/- )and Dgat1(+/+ )C57Bl/6 mice fed on either standard chow or a high fat diet. RESULTS: Body fat content was lower in the Dgat1(-/- )than the Dgat1(+/+ )mice in both experiments; lean body mass was higher in male Dgat1(-/- )than Dgat1(+/+ )mice fed on the high fat diet. Energy intake and expenditure were higher in male Dgat1(-/- )than Dgat1(+/+ )mice; these differences were less marked or absent in females. The body fat content of female Dgat1(+/- )mice was intermediate between that of Dgat1(-/- )and Dgat1(+/+ )mice, whereas male Dgat1(+/- )mice were similar to or fatter than Dgat1(+/+ )mice. Glucose tolerance was improved and plasma insulin reduced in Dgat1(-/- )mice fed on the high fat diet, but not on the chow diet. Both male and female Dgat1(+/- )mice had similar glucose tolerance to Dgat1(+/+ )mice. CONCLUSION: These results suggest that although ablation of DGAT1 improves glucose tolerance by preventing obesity in mice fed on a high fat diet, it does not improve glucose tolerance in mice fed on a low fat diet.