Ellagic Acid and Urolithin A Improve Insulin Sensitivity in Diet-Induced Insulin Resistant Mice and Reduce Detrimental Effects of Palmitate Administration in Differentiated C2C12 Myotubes.
Insulin resistance has been spreading as food and sedentary lifestyles are becoming more common. Major bodily complications often result, necessitating a search for affordable solutions. Phytochemicals are commonly used in alternative medicine but less so in areas where obesity and T2D prevail. This thesis studies ellagic acid (EA) and its metabolite urolithin A (UA) as potential treatments for insulin resistance, focusing on the main site of glucose uptake, skeletal muscle. In diet-induced insulin-resistant mice, long-term dietary EA&UA administration reduced glucose levels in IPITTs, while UA alone also reduced serum FFA and fasting glucose levels. Mitochondrial turnover and ROS detoxification markers increased with treatment, indicating improved mitochondrial quality control. Differentiated C2C12 mouse myotubes were utilized to study cellular effects of EA and UA. In insulin resistant myotubes, treatment enhanced ATP production and reduced ROS, cytotoxicity, and apoptosis. With insulin, UA increased uncoupled respiration while decreasing ROS, implying increased fuel oxidation without adding oxidative stress. UA tended to decrease glucose uptake as it increased cellular respiration, suggesting a stronger utilization of fatty acids. The results of this thesis support EA and UA as promising treatments for insulin resistance and the metabolic syndrome.