CIDEA 通过靶向 AMPK/PPARγ 轴和调节 SREBP1 调节牛乳腺上皮细胞中的从头脂肪酸合成,Journal of Agricultural and Food Chemistry

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CIDEA 通过靶向 AMPK/PPARγ 轴和调节 SREBP1 调节牛乳腺上皮细胞中的从头脂肪酸合成
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2022-08-30 , DOI: 10.1021/acs.jafc.2c05226
Ji Cheng ₁ , Dianwen Xu ₁ , Lisha Chen ₁ , Wenjin Guo ₁ , Guiqiu Hu ₁ , Juxiong Liu ₁ , Shoupeng Fu ₁

Affiliation

细胞死亡诱导 DNA 片段化因子-α 样效应物 A (CIDEA) 是一种脂滴相关蛋白，有助于促进小鼠和人类脂肪细胞的脂质代谢。然而，关于CIDEA对奶牛乳腺脂质代谢调控机制的研究较少。因此，本研究研究了 CIDEA 在牛乳腺上皮细胞 (bMEC) 中的作用。与低脂奶牛相比，高脂奶牛乳腺中 CIDEA 的表达水平显着升高。体外结果在 bMECs 中的研究表明，抑制 CIDEA 会抑制脂肪酸合成相关基因和甘油三酯 (TAG) 合成相关基因的表达。相反，CIDEA的过表达导致TAG和脂肪酸含量的增加。机理研究结果表明，CIDEA 的过表达抑制 AMP 活化蛋白激酶 (AMPK) 活性，从而增强过氧化物酶体增殖物激活受体-γ (PPARγ) 的表达，从而增加 TAG 含量。此外，CIDEA 的过表达促进了甾醇调节元件结合蛋白 1 (SREBP1) 的核转位。因此，本研究为通过营养和CIDEA的激素靶向调控奶牛脂质代谢提供了理论框架。

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CIDEA Regulates De Novo Fatty Acid Synthesis in Bovine Mammary Epithelial Cells by Targeting the AMPK/PPARγ Axis and Regulating SREBP1

Cell-death-inducing DNA fragmentation factor-α-like effector A (CIDEA) is a lipid-droplet-associated protein that helps to promote lipid metabolism in adipocytes of mice and humans. However, studies on the regulatory mechanism of CIDEA on lipid metabolism in the mammary glands of dairy cows are rare. Therefore, the role of CIDEA in bovine mammary epithelial cells (bMECs) was investigated in this study. The CIDEA expression levels in the mammary glands of high-fat-milk-producing cows were significantly higher compared to those in low-fat-milk-producing cows. Results of in vitro studies in bMECs showed that the inhibition of CIDEA inhibited the expression of fatty acid synthesis-related genes and triglyceride (TAG) synthesis-related genes. Conversely, the overexpression of CIDEA leads to an increase in the content of TAG and fatty acid. The results of mechanistic studies indicated that the overexpression of CIDEA inhibits AMP-activated protein kinase (AMPK) activity, which enhances the expression of peroxisome proliferator-activated receptor-γ (PPARγ) and consequently increases the TAG content. Furthermore, the overexpression of CIDEA promoted the nuclear translocation of sterol regulatory element-binding protein 1 (SREBP1). Therefore, a theoretical framework is provided by this study for the regulation of lipid metabolism in dairy cows by means of nutrition and the hormone targeting of CIDEA.

更新日期：2022-08-30

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