Flaxseed lignan secoisolariciresinol diglucoside improves insulin sensitivity through upregulating GLUT4 expression in diet-induced obese mice

Flaxseed Lignan Secoisolariciresinol Diglucoside Improves Insulin Sensitivity through Upregulating GLUT4 Expression in Diet-Induced Obese Mice Yanwen Wang1, Bourlaye Fofana2, Moumita Roy1, and Kaushik Ghose 2 1 Aquatic and Crop Resource Development, National Research Council of Canada, Charlottetown, PE, Canada C1A 4P3 2 Agriculture and Agri-Food Canada, Charlottetown, PE, Canada C1A 4P3 The objective of this study was to determine the anti-diabetic effect and underlying mechanisms of flaxseed lignans in diet-induced obese and insulin resistant mice. Male C57BL/6J mice, at the age of 8 wk, were provided with a high-fat diet to induce insulin resistance. The age-matched male C57BL/6J mice fed in parallel with a low-fat diet were used as the normal control. After 12 wk, the high-fat diet-fed mice were randomized into 4 groups and treated by gavage feeding once a day with 0 (high-fat/insulin resistant control), 10, 100, and 1,000 mg/kg/d of secoisolariciresinol diglucoside (SDG, 60% pure) lignan dissolved in water, respectively, for 6 weeks. The high-fat and low-fat control groups were gavaged with the vehicle. It was demonstrated that oral administration of SDG lowered body weight, serum insulin, total cholesterol and free fatty acid levels. SDG also improved oral glucose tolerance and insulin tolerance. Further molecular experiments showed that SDG increased muscle GLUT4 protein expression. The results suggest that flaxseed SDG lignan protects from insulin resistance in diet-induced obese mice and has potential to be used as a natural product for the prevention and treatment of obesity-related insulin resistance or diabetes.