Oral administration of interferon tau enhances oxidation of energy substrates and reduces adiposity in Zucker diabetic fatty rats.

Male Zucker diabetic fatty (ZDF) rats were used to study effects of oral administration of interferon tau (IFNT) in reducing obesity. Eighteen ZDF rats (28 days of age) were assigned randomly to receive 0, 4, or 8 μg IFNT/kg body weight (BW) per day (n = 6/group) for 8 weeks. Water consumption was measured every two days. Food intake and BW were recorded weekly. Energy expenditure in 4-, 6-, 8-, and 10-week-old rats was determined using indirect calorimetry. Starting at 7 weeks of age, urinary glucose, and ketone bodies were tested daily. Rates of glucose and oleate oxidation in liver, brown adipose tissue, and abdominal adipose tissue, as well as leucine catabolism in skeletal muscle, and lipolysis in white and brown adipose tissues were greater for rats treated with 8 μg IFNT/kg BW/day in comparison with control rats. Treatment with 8 μg IFNT/kg BW/day increased heat production, reduced BW gain and adiposity, ameliorated fatty liver syndrome, delayed the onset of diabetes, and decreased concentrations of glucose, free fatty acids, triacylglycerol, cholesterol, and branched-chain amino acids in plasma, compared with control rats. Oral administration of 8 µg IFNT/kg BW/day ameliorated oxidative stress in skeletal muscle, liver, and adipose tissue, as indicated by decreased ratios of oxidized glutathione to reduced glutathione and increased concentrations of tetrahydrobiopterin. These results indicate that IFNT stimulates oxidation of energy substrates and reduces obesity in ZDF rats and may have broad important implications for preventing and treating obesity-related diseases in mammals.