Resveratrol improves insulin resistance of catch-up growth by increasing mitochondrial complexes and antioxidant function in skeletal muscle

Abstract Caloric restriction followed by refeeding, a phenomenon known as catch-up growth (CUG), affects mitochondrial function and results in systemic insulin resistance (IR). We investigated the potential of resveratrol (RES) in CUG to prevent IR by increasing activity of the mitochondrial respiratory chain and antioxidant enzymes in skeletal muscle. Rats (8 weeks of age) were divided into 3 groups: normal chow, CUG, and CUG with RES intervention. Skeletal muscle and systemic IR were measured in each group after 4 and 8 weeks. Mitochondrial biogenesis and function, oxidative stress levels, and antioxidant enzyme activity in skeletal muscle were assessed. Catch-up growth–induced IR resulted in significant reductions in both average glucose infusion rate 60-120 at euglycemia and skeletal muscle glucose uptake. Mitochondrial citrate synthase activity was lower; and the activity of complexes I to IV in the intermyofibrillar and subsarcolemmal (SS) mitochondria were reduced by 20% to 40%, with the decrease being more pronounced in the SS fraction. Reactive oxygen species levels were significantly higher in intermyofibrillar and SS mitochondria, whereas activities of antioxidant enzymes were decreased. Oral administration of RES, however, increased silent information regulator 1 activity and improved mitochondrial number and insulin sensitivity. Resveratrol treatment decreased levels of reactive oxygen species and restored activities of antioxidant enzymes. This study demonstrates that RES protects insulin sensitivity of skeletal muscle by improving activities of mitochondrial complexes and antioxidant defense status in CUG rats. Thus, RES has therapeutic potential for preventing CUG-related metabolic disorders.