Ecomri

The mice used in this study were females and were maintained in the Mayo Clinic Animal Breeding facility. All experimental protocols were approved by the Mayo Clinic Institutional Animal Care and Use Committee. For the metabolic studies, mice were fed ad libitum a normal control diet (diet No. 3807; KLIBA-NAFAG), a high-fat diet (AIN-93G, modified to provide 60% of calories from fat; Dyets, Inc.), or a Western diet (TD.88137; 42% fat, 0.2% cholesterol; Harlan Laboratories). Body weight was recorded weekly. Food intake was measured for 7 consecutive days, with no difference detected between groups. Fat accumulation was measured by MRI (EcoMRI; EchoMedical Systems, Houston, TX) or by microcomputed tomography (micro-CT) scan (vivaCT40; SCANCO Medical, Zurich, Switzerland). For insulin tolerance testing, mice were food starved for 6 h before receiving a single intraperitoneal insulin injection (0.5 units/kg). Glycemia was measured from the tail vein. For survival experiments, mice were fed the normal chow diet until 6 months of age and were switched to the high-fat diet. Kaplan-Meier curves were generated using more than 20 mice per group. In all experiments, only litter mates were used.