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Ellagic Acid and Its Microbial Metabolite Urolithin A Alleviate Diet‐Induced Insulin Resistance in Mice
Author(s) -
Yang Jieping,
Guo Yuanqiang,
Henning Susanne M.,
Chan Brenda,
Long Jianfeng,
Zhong Jin,
AcinPerez Rebeca,
Petcherski Anton,
Shirihai Orian,
Heber David,
Li Zhaoping
Publication year - 2020
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.202000091
Subject(s) - ellagic acid , insulin resistance , chemistry , medicine , metabolite , endocrinology , adiponectin , metabolism , insulin , carbohydrate metabolism , biochemistry , biology , antioxidant , polyphenol
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.