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

Abstract

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, 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 to 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 the antioxidant 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.

Interferon Tau Alleviates Obesity-Induced Adipose Tissue Inflammation and Insulin Resistance by Regulating Macrophage Polarization

“…An effective IFNT dose was chosen based on previous studies [37]. After 12 weeks feeding, IFNT treatment did not significantly affect body weight gain or food intake in either HFD or LFD groups (Figure 1A, B).…”

The role of leucine and its metabolites in protein and energy metabolism

“…When mitochondrial function is impaired in obese or diabetic animals, the concentrations of BCAA in the plasma are markedly elevated (Fu et al 2005;Jobgen et al 2006, Tekwe et al 2013Wu et al 2007a, b). In contrast, improvements in mitochondrial function prevents such as increase in BCAA in obese or diabetic subjects (Tekwe et al 2013, Yang et al 2015.…”

“…In contrast, improvements in mitochondrial function prevents such as increase in BCAA in obese or diabetic subjects (Tekwe et al 2013, Yang et al 2015. Furthermore, mitochondria play a key role in mediating adipocyte lipid metabolism and cellular energy metabolism (Vankoningsloo et al 2005).…”

Chronicling the discovery of interferon tau

“…Recognizing the link between inflammation, obesity and the anti-inflammatory properties of IFNT, studies were initiated to determine effects of oral IFNT on time of onset of Type 2 diabetes (T2D), oxidation of glucose and fatty acids in insulin-sensitive tissues, energy expenditure, body mass, and tissue weights in Zucker diabetic fatty (ZDF) rats, an animal model of T2D and obesity (see Tekwe et al 2013). Oral administration of IFNT (8μg/kg body weight/day) reduced oxidative stress, increased oxidation of energy substrates to CO 2 in insulin-sensitive tissues, decreased white adipose tissue by 40%, increased brown adipose tissue by 46%, increased whole-body energy expenditure, and ameliorated oxidative stress in insulin-sensitive tissues (i.e., decreased ratios of oxidized to reduced glutathione), and increased concentrations of the antioxidant tetrahydrobiopterin.…”

“…Oral administration of IFNT (8μg/kg body weight/day) reduced oxidative stress, increased oxidation of energy substrates to CO 2 in insulin-sensitive tissues, decreased white adipose tissue by 40%, increased brown adipose tissue by 46%, increased whole-body energy expenditure, and ameliorated oxidative stress in insulin-sensitive tissues (i.e., decreased ratios of oxidized to reduced glutathione), and increased concentrations of the antioxidant tetrahydrobiopterin. Collectively, metabolic profiles were improved (Tekwe et al 2013). Because IFNT stimulates oxidation of energy substrates and reduces obesity in ZDF rats, IFNT has important implications for treating obesity-related diseases.…”