Oral administration of α‐ketoglutarate or interferon‐τ reduces adiposity in diet‐induced obese rats

Abstract

Obesity is a risk factor for many chronic diseases, including hypertension, type‐2 diabetes, and cancer. High levels of branched‐chain amino acids (BCAA) in plasma are commonly associated with endothelial dysfunction in obesity. This study tested the hypothesis that dietary supplementation with á‐ketoglutarate (AKG) or interferon‐ô (IFNT) may stimulate BCAA catabolism in tissues, thereby reducing the circulating levels of BCAA and increasing NO synthesis by EC. Beginning at 4 wk of age, male Sprague‐Dawley rats were fed a low‐fat (LF) or high‐fat (HF) diet for 15 wk. At 19 wk of age, lean or obese rats continued to be fed their respective diets and received drinking water containing either 0 or 1% AKG, or 80 μg IFNT/100 mL (n=8/group). At 31 wk of age, rats were euthanized to obtain tissues. Water consumption (25 mL/kg BW per day) or food intake did not differ among the three groups of rats. Oral administration of AKG (250 mg/kg BW per day) or IFNT (20 μg/kg BW per day) reduced (P<0.05) concentrations of BCAA in plasma, adiposity, and glutamine: fructose‐6‐phosphate transaminase activity in EC, and enhanced (P<0.05) whole‐body insulin sensitivity and NO synthesis by EC, in LF and HF rats. AKG administration reduced (P<0.05) body weights of LF and HF rats, as did IFNT on LF rats. These results indicate that AKG or IFNT can reduce adiposity and increase NO production by EC in diet‐induced obese rats. (Supported by AHA and NIH grants).