Scope加州大学洛杉矶分校戴维·格芬医学院的Jieping Yang、Yuanqiang Guo和Zhaoping Li*等人旨在评价膳食鞣花酸（ellagic acid，EA）及其微生物代谢物尿石素 A (urolithin A，UA)对饮食诱导的胰岛素抵抗的小鼠体内葡萄糖代谢和胰岛素抵抗（insulin resistance，IR）的影响。
Methods and Results用高脂/高糖饮食（high fat/high sucrose diet，HF / HS）喂养DBA2J小鼠8周以诱导IR，然后将0.1％EA、UA或EA和UA组合（EA + UA）添加到HF / HS饮食中再持续8周。与HF / HS对照相比，UA可以显著降低空腹血糖并增加脂联素。与HFHS对照组相比，在腹腔胰岛素耐受性测试中，EA+UA在15分钟和120分钟可显著改善胰岛素介导的降糖作用，并降低了血液甘油三酯。血清游离脂肪酸被EA、UA和EA + UA显著降低。在肝脏和骨骼肌中，观察到与EA、UA和EA + UA的线粒体功能相关的基因的差异表达。与健康对照相比，IR小鼠的原代肝细胞具有更高的质子泄漏率、基础耗氧量和ATP耗氧量。EA和EA+UA对IR小鼠肝细胞的质子泄漏有明显的抑制作用，但UA不能。ConclusionEA和UA能对IR小鼠产生不同的代谢益处。EA和UA对线粒体功能的影响提示了一种可能的代谢调节机制。
Abstract
Ellagic Acid and Its Microbial Metabolite Urolithin A Alleviate Diet‐Induced Insulin Resistance in Mice
Jieping Yang, Yuanqiang Guo, Susanne M. Henning, Brenda Chan, Jianfeng Long, Jin Zhong, Rebeca Acin‐Perez, Anton Petcherski, Orian Shirihai, David Heber, Zhaoping Li
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 combined (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 has 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.
该文章《Ellagic Acid and Its Microbial Metabolite Urolithin A Alleviate Diet‐Induced Insulin Resistance in Mice》于《Molecular Nutrition》2020年8月出版。
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