Circulating exosome-mediated AMPKα-SIRT1 pathway regulates lipid metabolism disorders in calf hepatocytes

文献类型： 外文期刊

第一作者： Zhang, Daoliang

作者： Zhang, Daoliang;Liu, Chang;Huang, Yingying;Tai, Wenjun;Feng, Shibin;Wang, Xichun;Zhao, Chang;Li, Yu;Ding, Hongyan

作者机构：

关键词： Dairy cow ketosis; Circulating exosome; Lipid metabolism disorder; AMPK alpha-SIRT1 pathway

期刊名称：RESEARCH IN VETERINARY SCIENCE （ 影响因子：2.4； 五年影响因子：2.5 ）

ISSN： 0034-5288

年卷期： 2024 年 169 卷

页码：

收录情况： SCI

摘要： Subclinical ketosis (SCK) in dairy cows is often misdiagnosed because it lacks clinical signs and detection indicators. However, it is highly prevalent and may transform into clinical ketosis if not treated promptly. Due to the negative energy balance, a large amount of fat is mobilized, producing NEFA that exceeds the upper limit of liver processing, which in turn leads to the disturbance of liver lipid metabolism. The silent information regulator 1 (SIRT1) is closely related to hepatic lipid metabolism disorders. Exosomes as signal transmitters, also play a role in the circulatory system. We hypothesize that the circulating exosome-mediated adenosine 5 '-mono-phosphate (AMP)-activated protein kinase alpha (AMPK alpha)-SIRT1 pathway regulates lipid metabolism disorders in SCK cows. We extracted the exosomes required for the experiment from the peripheral circulating blood of non-ketotic (NK) and SCK cows. We investigated the effect of circulating exosomes on the expression levels of mRNA and protein of the AMPK alpha-SIRT1 pathway in non-esterified fatty acid (NEFA)-induced dairy cow primary hepatocytes using in vitro cell experiments. The results showed that circulating exosomes increased the expression levels of Lipolysis-related genes and proteins (AMPK alpha, SIRT1, and PGC-1 alpha) in hepatocytes treated with 1.2 mM NEFA, and inhibited the expression of lipid synthesis-related genes and protein (SREBP-1C). The regulation of exosomes on lipid metabolism disorders caused by 1.2 mM NEFA treatment showed the same trend as for SIRT1-overexpressing adenovirus. The added exosomes could regulate NEFA-induced lipid metabolism in hepatocytes by mediating the AMPK alpha-SIRT1 pathway, consistent with the effect of transfected SIRT1 adenovirus.

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