S100A16, a novel lipogenesis promoting factor in livers of mice and hepatocytes in vitro
S100A16, a novel lipogenesis promoting factor in livers of mice and hepatocytes in vitro
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S100A16，一种新型体外小鼠肝脏和肝细胞脂肪生成促进因子
DOI：
10.1002/jcp.28748
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发表时间：
2019-11-01
影响因子：
5.6
通讯作者：
Liu, Yun
中科院分区：
文献类型：
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作者：
Kan, Jingbao;Zhao, Cuiping;Liu, Yun
为了研究S100钙结合蛋白A16（S100A16）在肝脏脂质代谢中的作用，对S100a16转基因小鼠、S100a16基因敲低小鼠和野生型C57BL/6小鼠分别喂食高脂饮食（HFD）或正常脂肪饮食（NFD）16周。结果显示，对于喂食HFD的小鼠，S100a16转基因小鼠比其他喂食HFD的小鼠表现出明显更严重的脂肪肝，血清甘油三酯（TG）浓度显著升高，肝脏中有更多且更大的脂滴，而S100a16基因敲低小鼠则完全相反，肝脏脂肪病变和TG血清学变化最轻；对于喂食NFD的小鼠，肝脏脂肪堆积和血清TG浓度显著低于喂食HFD的小鼠，且肝脏中未发现明显的脂滴。此外，我们发现钙调蛋白（CaM）与S100A16相互作用，S100A16是腺苷酸活化蛋白激酶（AMPK）通路的一个成员。我们的研究发现，S100A16通过与CaM相互作用调节AMPK通路相关蛋白，从而调节肝脏脂质合成。S100A16通过CaM/CAMKK2/AMPK通路调节肝脏脂质代谢。S100A16的过表达促进HFD诱导的脂肪肝恶化，而S100A16的低表达可减轻脂肪肝。
To investigate the role of S100 calcium-binding protein A16 (S100A16) in hepatic lipid metabolism, S100a16 transgenic, S100a16 knockdown, and wildtype C57BL/6 mice were fed either a high-fat diet (HFD) or normal-fat diet (NFD) for 16 weeks. The results showed that for HFD-fed mice, S100a16 transgenic mice showed significantly more severe fatty liver than other HFD-fed mice, with a significant increase in serum triglyceride (TG) concentration, with more and larger lipid droplets in the liver, whereas S100a16 knockdown mice were completely opposite, with liver fat lesions and TG serological changes being the mildest; for NFD-fed mice, liver fat accumulation and serum TG concentrations were significantly lower than those fed HFD, and no significant lipid droplets were found in the liver. Further, we found that calmodulin (CaM) interacts with S100A16, a member of the AMP-activated protein kinase (AMPK) pathway. Our research found that S100A16 regulates the AMPK pathway-associated protein by interacting with CaM to regulate liver lipid synthesis. S100A16 regulates liver lipid metabolism through the CaM/CAMKK2/AMPK pathway. Overexpression of S100A16 promotes the deterioration of fatty liver induced by HFD, and low expression of S100A16 can attenuate fatty liver.