These transgenic mice express mouse Dgat1 (diacylglycerol O-acyltransferase 1), FLAG epitope amino-terminal tagged, under the control of the white adipose tissue specific mouse Fabp4 (fatty acid binding protein 4, adipocyte) promoter. In this founder line 2 (high expressing line) Dgat1 protein and mRNA levels are increased two fold in white apidose tissue and increased ~6?8.5 fold in peritoneal macrophages. Transgenic mice have adipocytes that are larger in size and mass than wildtype controls and elevated triglyceride levels in the reproductive fat pads. On either a chow or high fat diet, transgenic mice have a greater mean total fat pad weight than controls. When fed a high fat diet for 4 weeks, transgenic mice exhibit hyperphagy, higher body weight, elevated serum free fatty acid levels and lower serum triglyceride levels when compared to wildtype controls. Serum glucose and insulin levels, and liver and skeletal muscle triglyceride levels of transgenic and wildtype mice on the high fat diet are similar. Transgenic mice on a high fat diet for 16 weeks exhibit less triacylglycerol levels in liver and skeletal muscle, enhanced glucose and insulin tolerance, lower insulin and glucose fasting levels, and reduced macrophage recruitment into and inflammation of white adipose tissue. Mice hemizygous for the transgenic insert are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. The Donating Investigator has not attempted to make this strain homozygous.
