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Open Access Publications from the University of California

Scholarly Works (2 results)

  • Thesis
  • Peer Reviewed
UCLA Electronic Theses and Dissertations (2018)

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.

    Cover page: 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.
    • Article
    • Peer Reviewed
    UCLA Previously Published Works (2020)

    Scope

    This work aims at evaluating the effect of dietary ellagic acid (EA) and its microbial metabolite urolithin A (UA) on glucose metabolism and insulin resistance (IR) in mice with diet-induced IR.

    Methods and results

    DBA2J mice are fed a high fat/high sucrose diet (HF/HS) for 8 weeks to induce IR and then 0.1% EA, UA, or EA and UA (EA+UA) are added to the HF/HS-diet for another 8 weeks. UA significantly decreases fasting glucose and increases adiponectin compared with HF/HS-controls. During intraperitoneal insulin tolerance test, EA+UA significantly improve insulin-mediated glucose lowering effects at 15 and 120 min and reduce blood triglycerides compared with HF/HS-controls. Serum free fatty acids are significantly decreased by EA, UA, and EA+UA. Differential expression of genes related to mitochondrial function by EA, UA, and EA+UA in liver and skeletal muscle is observed. Primary hepatocytes from IR-mice have higher proton leak, basal and ATP-linked oxygen consumption rates compared with healthy controls. EA and EA+UA but not UA reduce the proton leak in hepatocytes from IR-mice.

    Conclusion

    EA and UA induce different metabolic benefits in IR mice. The effects of EA and UA on mitochondrial function suggest a potentially novel mechanism modulating metabolism.
      Cover page: Ellagic Acid and Its Microbial Metabolite Urolithin A Alleviate Diet‐Induced Insulin Resistance in Mice
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