Oral administration of interferon‐τ reduces adiposity in Zucker diabetic fatty rats

Abstract

The Zucker diabetic fatty (ZDF) rat spontaneously develops type‐2 diabetes at 7 to 8 weeks of age. This study tested the hypothesis that oral administration of Interferon‐ô (IFNT) reduces obesity and delay the onset of diabetes in ZDF rats. Beginning at 4 weeks of age, 18 male ZDF rats were fed a Purina 5008 diet and received drinking water containing 0, 330 and 660 ng IFNT/100 mL (n=6/group), providing 0, 4 and 8 μg IFNT/kg BW per day. At 12 weeks of age, rats were euthanized to obtain tissues. Water or food intake did not differ (P > 0.05) among the three groups of rats. Compared to the control group, oral administration of 8 μg IFNT/kg BW per day reduced (P < 0.05) the body weight of the rats by 6.2%, the onset of diabetes by 8.5 days, concentrations of branched‐chain amino acids by 28%, and white adipose tissue by 40%, while increasing (P < 0.05) brown adipose tissue (BAT) in the interscapular region by 46%. Oral administration of 8 μg IFNT/kg BW per day enhanced (P < 0.05): 1) glucose oxidation in the liver, BAT, and white adipose tissue; 2) oleate oxidation in the liver, gastrocnemius muscle and BAT; and 3) leucine transamination in skeletal muscle. None of the measured variables differed (P > 0.05) between the rats receiving oral administration of 0 and 4 μg IFNT/kg BW per day. Our results indicate that IFNT at 8 μg IFNT/kg BW per day reduced obesity and improved the metabolic profile in ZDF rats. (Supported by AHA and NIH grants)