Dietary wolfberry increases hepatic insulin sensitivity in obese mice

Objective To determine whether dietary wolfberry reverses insulin resistance in obese mice. Methods Male C57BL/6J mice, at 6 weeks of age, were divided into 3 groups, 15 mice for each group, for a 28‐week dietary study. Three different diets were 10 kcal % fat diets as a low fat diet control, 45 kcal % fat diets (high fat diet), and high fat diets with 1 % (kcal/kcal) wolfberry fruits. Food consumption, body weight and fasting blood glucose were monitored weekly. At termination of study, 6 mice from each group were subjected to test of oral glucose tolerance and insulin resistance. The rest mice were euthanized for biochemical analysis. Liver oxidative stress was determined by production of reactive oxygen species (ROS). Uncoupling protein UCP2, ER stress biomarkers, IRS‐1 and IRS‐2, AKT, and acetyl‐CoA carboxylase (ACC) were determined by Western blotting. Results Mice fed high fat diets developed obesity, hyperlipidemia, and hepatic steatosis. High fat diets induced elevation of ROS levels, decreases of UCP2, activation of ACC and ER stress. Dietary wolfberry attenuated oxidative stress and ER stress, and increased insulin sensitivity. However, hepatic steatosis was not altered. Conclusions Wolfberry at 1 % (kcal/kcal) increases hepatic insulin sensitivity in obese mice most likely through attenuating cellular oxidative stress and subsequent ER stress. Hepatic insulin resistance is independent of steatosis. Grant Funding Source: National Institutes of Health COBRE Grant P20‐RR‐017686