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

Abstract

Abstract 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.