Abstract 398: Mice Containing the Human Gilbert’S Syndrome Mutation (UGT1A1*28) Are Resistant to the Development of Type II Diabetes and Deposition of Body Fat on a High Fat Diet

Heme oxygenase-1 (HO-1) induction has been previously demonstrated to reduce body weight and prevent type II diabetes in obese mice. However, the role of increased bilirubin production in this response is unknown. Gilbert’s syndrome is derived from a mutation in the hepatic UGT1A1 gene which results in decreased conjugation and increased levels of plasma biliribin independent of changes in HO-1. In order to determine the role of increased plasma bilirubin on the development of type II diabetes and obesity, we placed mice whose only functioning UGT1A1 gene contained the human Gilbert’s syndrome mutation (UGT1A1*28, n=4) as well as C57BL/6J control mice (n=5) on a high fat (60%) diet for 35 weeks. Plasma bilirubin levels were significantly increased in the UGT*28 mice as compared to controls and averaged 1.65 ± 0.2 vs. 1.18 ± 0.1 mg/dL (P