Improving Glucose Metabolism With Resveratrol in a Swine Model of Metabolic Syndrome Through Alteration of Signaling Pathways in the Liver and Skeletal Muscle

Hypothesis: We hypothesized that supplemental resveratrol would affect glucose metabolism in the skeletal muscle and liver to improve blood glucose control. Design: Case-control study. Setting: Hospital laboratory. Subjects: Yorkshire miniswine. Intervention: The swine developed metabolic syndrome by consuming a high-calorie, high-fat/cholesterol diet for 11 weeks. Pigs were fed either a normal diet (control) (n=7), a hypercholesterolemic diet (HCC) (n=7), or a hypercholesterolemic diet with supplemental resveratrol (100 mg/kg/d) (HCRV) (n=7). Animals underwent dextrose challenge prior to euthanasia and tissue collection. Main Outcome Measures: Measurements of glucose and insulin levels, skeletal muscle and liver protein expression, and liver function test results. Results: The HCC group had significantly increased blood glucose levels at 30 minutes as compared with the control and HCRV groups. The HCC group demonstrated increased fasting serum insulin levels and levels of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase. Oil red O staining demonstrated increased lipid deposition in the livers of the HCC animals. Immunoblotting in the liver showed increased levels of mammalian target of rapamycin, insulin receptor substrate 1, and phosphorylated AKT in the HCRV group. Immunoblotting in skeletal muscle tissue demonstrated increased glucose transporter type 4 (Glut 4), peroxisome proliferating activation receptor gamma coactivator 1 alpha, peroxisome proliferator-activated receptor alpha, peroxisome proliferator-activated receptor gamma, and phosphorylated AKT at threonine 308 expression as well as decreased retinol binding protein 4 in the HCRV group. Immunofluorescence staining for Glut 4 in the skeletal muscle demonstrated increased Glut 4 staining in the HCRV group compared with the HCC or control groups. Conclusion: Supplemental resveratrol positively influences glucose metabolism pathways in the liver and skeletal muscle and leads to improved glucose control in a swine model of metabolic syndrome.