Prevention of skeletal muscle insulin resistance by dietary cod protein inhigh fat-fed rats

In the present study, we tested the hypothesis that fish protein may repres ent a key constituent of fish with glucoregulatory activity. Three groups o f rats were fed a high-fat diet in which the protein source was casein, fis h (cod) protein, or soy protein; these groups were compared with a group of chow-fed controls. High-fat feeding led to severe whole body and skeletal muscle insulin resistance in casein- or soy protein-fed rats, as assessed b y the euglycemic clamp technique coupled with measurements of 2-deoxy-D-[H- 3] glucose uptake rates by individual tissues. However, feeding cod protein fully prevented the development of insulin resistance in high fat-fed rats . These animals exhibited higher rates of insulin-mediated muscle glucose d isposal that were comparable to those of chow-fed rats. The beneficial effe cts of cod protein occurred without any reductions in body weight gain, adi pose tissue accretion, or expression of tumor necrosis factor-alpha in fat and muscle. Moreover, L6 myocytes exposed to cod protein-derived amino acid s showed greater rates of insulin-stimulated glucose uptake compared with c ells incubated with casein- or soy protein-derived amino acids. These data demonstrate that feeding cod protein prevents obesity-induced muscle insuli n resistance in high fat-fed obese rats at least in part through a direct a ction of amino acids on insulin-stimulated glucose uptake in skeletal muscl e cells.