l-Arginine supplementation regulates energy-substrate metabolism in skeletal muscle and adipose tissue of diet-induced obese rats

Dietary supplementation with l-arginine has been reported to reduce white fat mass in diet-induced obese rats and in obese humans. This study was conducted to test the hypothesis that the arginine treatment regulates glucose and fatty acid metabolism in insulin-sensitive tissues. Male Sprague–Dawley rats (4-week-old) were fed either low- or high-fat diets for 15 weeks ( n = 16/diet). Thereafter, lean or obese rats were fed their respective diets and received drinking water containing either 1.51% l-arginine-HCl or 2.55% alanine (isonitrogenous control) ( n = 8/treatment group). After 12 weeks of treatment, rats were euthanized and tissue samples were collected for biochemical assays. High-fat feeding increased the size of adipocytes isolated from retroperitoneal (RP) adipose tissue, while arginine treatment reduced their size. The total number of adipocytes in the adipose tissue did not differ among the four groups of rats. Glucose oxidation in extensor digitorum longus (EDL) muscle, soleus muscle, and RP adipose tissue were reduced in response to high-fat feeding. On the contrary, oleic acid oxidation in RP adipose tissue was enhanced in rats fed the high-fat diet. Arginine treatment stimulated both glucose and oleic acid oxidation in EDL and soleus muscles, while having no effect on glucose oxidation, oleic acid oxidation, or basal lipolysis per 106 adipocytes in RP adipose tissue. Collectively, these results indicate that oral supplementation with arginine to diet-induced obese rats promoted the oxidation of energy substrates in skeletal muscle, thereby reducing white fat in the body.