Metabolism-related fatty liver disease (MAFLD) is associated with abnormal fat accumulation in the liver. The exact mechanism underlying the occurrence and development of MAFLD remains to be elucidated. Here, we discovered that the expression of Sucrose non-fermenting-related kinase (SNRK) is elevated in the liver of the MAFLD population. Mice deficient in SNRK exhibited damage to fatty acid oxidation and persistent accumulation of lipids in the liver. Pharmacological inhibition of the mTOR pathway in SNRK-deficient mice restored autophagy and improved lipid accumulation. In terms of mechanism, we observed that SNRK binds to the raptor component of mTOR complex 1, promoting fatty acid oxidation in the liver by activating autophagy. Overexpression of SNRK in high-fat diet-induced obese mice restored autophagy and ameliorated lipid accumulation. Notably, we also demonstrated that overexpression of SNRK significantly enhanced fatty acid oxidation in the mouse liver. We further confirmed that SNRK is essential for the liver to regulate autophagy and fatty acid oxidation. These findings underscore the importance of SNRK's potential in the treatment of MAFLD.

中文翻译：

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SNRK 调节 MAFLD 中肝脏脂质稳态的 mTOR 自噬途径。


代谢相关脂肪肝 （MAFLD） 与肝脏中的异常脂肪堆积有关。MAFLD 发生和发展的确切机制仍有待阐明。在这里，我们发现蔗糖非发酵相关激酶 （SNRK） 的表达在 MAFLD 人群的肝脏中升高。缺乏 SNRK 的小鼠表现出脂肪酸氧化损伤和脂质在肝脏中的持续积累。SNRK 缺陷小鼠 mTOR 通路的药理学抑制恢复了自噬并改善了脂质积累。在机制方面，我们观察到 SNRK 与 mTOR 复合物 1 的猛禽组分结合，通过激活自噬促进肝脏中的脂肪酸氧化。在高脂饮食诱导的肥胖小鼠中过表达 SNRK 可恢复自噬并改善脂质积累。值得注意的是，我们还证明 SNRK 的过表达显着增强了小鼠肝脏中的脂肪酸氧化。我们进一步证实 SNRK 对于肝脏调节自噬和脂肪酸氧化至关重要。这些发现强调了 SNRK 在治疗 MAFLD 中的潜力的重要性。