Center for Regenerative Medicine, Institute for Translational Medicine, Qingdao University, Qingdao, 266021, China.
Mol Nutr Food Res. 2019 Apr;63(7):e1801322. doi: 10.1002/mnfr.201801322. Epub 2019 Jan 18.
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.
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.
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.
高脂肪（HF）饮食诱导的胰岛素抵抗是心血管疾病发病机制的主要原因。然而，调节心脏胰岛素信号的分子机制尚不完全清楚。本研究旨在探讨 tafazzin 在 HF 饮食喂养小鼠心脏中的调节作用。
将小鼠喂食 HF 饮食或低脂（LF）饮食长达 24 周。24 周后发现，HF 饮食诱导的心脏功能障碍与线粒体蛋白 tafazzin 的过度表达有关。tafazzin 的增加促进线粒体分裂，并损害胰岛素信号转导，这是由细胞质中的 dynamin 相关蛋白 1（Drp-1）向线粒体的易位介导的。此外，用 siRNA 敲低 tafazzin 可抑制棕榈酸诱导的线粒体分裂并恢复胰岛素敏感性。此外，还确定了作为靶向 tafazzin 的上游调节因子的 miR-125b-5p，并且发现棕榈酸盐诱导的胰岛素抵抗进一步得到挽救。
在 HF 饮食喂养的小鼠心脏中，tafazzin 通过介导 Drp-1 向线粒体的易位导致胰岛素抵抗，而小非编码 RNA miR-125b-5p 至少部分调节该信号通路并减轻胰岛素抵抗。
