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Increased Dynamin‐Related Protein 1–Dependent Mitochondrial Fission Contributes to High‐Fat‐Diet‐Induced Cardiac Dysfunction and Insulin Resistance by Elevating Tafazzin in Mouse Hearts
Author(s) -
Chang Wenguang,
Xiao Dandan,
Ao Xiang,
Li Mengyang,
Xu Tao,
Wang Jianxun
Publication year - 2019
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.201801322
Subject(s) - insulin resistance , mitochondrion , biology , mitochondrial fission , gene knockdown , microbiology and biotechnology , medicine , insulin , endocrinology , apoptosis , biochemistry
Scope High fat (HF)‐diet‐induced insulin resistance is a major contributor to the pathogenesis of cardiovascular diseases. However, the molecular mechanisms that regulate cardiac insulin signaling are not fully understood. The regulatory role of tafazzin in the hearts of HF‐diet‐fed mice is investigated. Methods and results Mice are fed a HF diet or low fat (LF) diet for up to 24 weeks. After 24 weeks, it is found that HF‐diet‐induced cardiac dysfunction is linked to overexpression of the mitochondrial protein tafazzin. Increased tafazzin promotes mitochondrial fission and impairs insulin signaling, which is mediated by dynamin‐related protein 1 (Drp‐1) translocation from the cytosol to the mitochondria. Furthermore, knockdown of tafazzin with siRNA inhibits palmitic‐acid–induced mitochondrial fission and restores insulin sensitivity. Moreover, miR‐125b‐5p as an upstream regulator targeting tafazzin is identified and palmitate‐induced insulin resistance further rescued. Conclusion In HF‐diet‐fed mouse hearts, increased tafazzin contributes to insulin resistance via mediating Drp‐1 translocation to the mitochondria, and a small non‐coding RNA, miR‐125b‐5p, at least partially regulates this signaling pathway and alleviates insulin resistance.