Saturated fatty acids (SFAs) (the "bad" fat), especially palmitate (PA), in the human diet are blamed for potential health risks such as obesity and cancer because of SFA-induced lipotoxicity. However, epidemiological results demonstrate a latent benefit of SFAs, and it remains elusive whether a certain low level of SFAs is physiologically essential for maintaining cell metabolic hemostasis. Here, we demonstrate that although high-level PA (HPA) indeed induces lipotoxic effects in liver cells, low-level PA (LPA) increases mitochondrial functions and alleviates the injuries induced by HPA or hepatoxic agent carbon tetrachloride (CCl4). LPA treatment in mice enhanced liver mitochondrial activity and reduced CCl4 hepatotoxicity with improved blood levels of aspartate aminotransferase (AST), alanine transaminase (ALT), and mitochondrial aspartate transaminase (m-AST). LPA-mediated mitochondrial homeostasis is regulated by CDK1-mediated SIRT3 phosphorylation, which in turn deacetylates and dimerizes CPT2 to enhance fatty acid oxidation. Thus, an advantageous effect is suggested by the consumption of LPA that augments mitochondrial metabolic homeostasis via CDK1-SIRT3-CPT2 cascade.

中文翻译：

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低水平饱和脂肪酸棕榈酸酯通过CDK1-SIRT3-CPT2级联促进线粒体代谢，从而有益于肝细胞。

由于SFA诱导的脂毒性，人们饮食中的饱和脂肪酸（SFA）（“坏”脂肪），尤其是棕榈酸酯（PA）可能引起健康隐患，例如肥胖症和癌症。然而，流行病学结果表明，SFA具有潜在的好处，而对于维持细胞代谢止血的生理必需水平而言，SFA的低水平是否在生理上仍是未知之数。在这里，我们证明尽管高水平的PA（HPA）确实会诱导肝细胞的脂毒性作用，但低水平的PA（LPA）会增加线粒体功能并减轻HPA或肝毒性剂四氯化碳（CCl4）引起的损伤。用LPA处理小鼠可提高肝脏线粒体活性并降低CCl4肝毒性，同时提高血液中的天冬氨酸转氨酶（AST），丙氨酸转氨酶（ALT）的水平，和线粒体天冬氨酸转氨酶（m-AST）。LPA介导的线粒体稳态由CDK1介导的SIRT3磷酸化调节，该磷酸化反过来使CPT2脱乙酰化并二聚化以增强脂肪酸氧化。因此，LPA的消耗通过CDK1-SIRT3-CPT2级联增加了线粒体代谢稳态而提示了有利的作用。