Low-Level Saturated Fatty Acid Palmitate Benefits Liver Cells by Boosting Mitochondrial Metabolism via CDK1-SIRT3-CPT2 Cascade
Low-Level Saturated Fatty Acid Palmitate Benefits Liver Cells by Boosting Mitochondrial Metabolism via CDK1-SIRT3-CPT2 Cascade
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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
DOI：
10.1016/j.devcel.2019.11.012
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发表时间：
2020-01-27
影响因子：
11.8
通讯作者：
Li, Jian Jian
中科院分区：
文献类型：
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作者：
Liu, Lin;Xie, Bowen;Li, Jian Jian
饱和脂肪酸（SFA）（“坏”脂肪），特别是棕榈酸（PA），在人类饮食中被指责为潜在的健康风险，如肥胖和癌症，因为SFA诱导的脂毒性。然而，流行病学的结果表明，潜在的好处，SFA，它仍然难以捉摸的是，一定的低水平的SFA是否是维持细胞代谢止血的生理必需的。在这里，我们证明，虽然高水平的PA（HPA）确实诱导肝细胞的脂毒性作用，低水平的PA（LPA）增加线粒体功能和加重HPA或肝毒性剂四氯化碳（CCl 4）诱导的损伤。小鼠中的LPA治疗增强了肝脏线粒体活性并降低了CCl 4的肝毒性，并改善了天门冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）和线粒体天门冬氨酸氨基转移酶（m-AST）的血液水平。LPA介导的线粒体稳态由CDK 1介导的SIRT 3磷酸化调节，SIRT 3磷酸化反过来使CPT 2脱乙酰化和二聚化以增强脂肪酸氧化。因此，通过消耗LPA表明了有利的效果，LPA通过CDK 1-SIRT 3-CPT 2级联增强线粒体代谢稳态。
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 (CCI4). LPA treatment in mice enhanced liver mitochondrial activity and reduced CCI4 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.