ACAT2 Is a Novel Negative Regulator of Pig Intramuscular Preadipocytes Differentiation.
ACAT2 Is a Novel Negative Regulator of Pig Intramuscular Preadipocytes Differentiation.
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ACAT2 是猪肌内前脂肪细胞分化的新型负调节因子
DOI：
10.3390/biom12020237
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发表时间：
2022-01-31
期刊：
影响因子：
5.5
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Tian Y;Zhao Y;Yu W;Melak S;Niu Y;Wei W;Zhang L;Chen J
肌内脂肪（IMF）被认为是沉积在肌肉纤维之间的脂肪。脂肪组织的细胞外基质微环境对脂肪细胞的分化、重塑和功能发挥至关重要。因此，本研究提取二花莲猪背最长肌肌肉组织离心液（MTF）模拟肌内前脂肪细胞微环境。低肌内脂肪水平猪的MTF可以抑制猪肌内前脂肪细胞分化。然后，利用蛋白质组学技术（iTRAQ）对不同IMF含量的MTF进行分析，发现IMF高的个体ACAT2（酰基辅酶a：胆固醇酰基转移酶2）水平低，而IMF低的个体ACAT2水平高。与脂肪和胆固醇代谢密切相关的辅酶A相关通路发生了显著变化。因此，我们推测ACAT2作为参与胆固醇代谢的重要元件，可能成为猪肌内前脂肪细胞分化机制的潜在分子标记物。猪肌内脂肪前细胞过表达ACAT2可抑制其分化，而添加ACAT2抑制剂avasimibe可挽救这一过程。敲低srebp2或ldlr这两个与ACAT2和胆固醇代谢密切相关的关键基因，可以抑制猪肌内前脂肪细胞的分化。总之，我们的研究结果表明，ACAT2是肌内脂肪细胞分化的一种新的负调节因子，通过调节参与胆固醇代谢的pparγ、cebpα信号和srebp2/ldlr信号。
Intramuscular fat (IMF) is considered as the fat deposited between muscle fibers. The extracellular matrix microenvironment of adipose tissue is of critical importance for the differentiation, remodeling and function of adipocytes. Therefore, in this study we extracted the muscle tissue centrifugal fluid (MTF) of the longissimus dorsi of Erhualian pigs to mimic the microenvironment of intramuscular pre-adipocytes. MTF of pigs with low intramuscular fat level can inhibit pig intramuscular pre-adipocytes differentiation. Then, proteomics technology (iTRAQ) was used to analyze the MTF with different IMF content, and it was found that individuals with high IMF had low ACAT2 (Acyl-CoA: cholesterol acyltransferases 2) levels, while individuals with low IMF had high ACAT2 levels. Significant changes took place in the pathways involved in coenzyme A, which are closely related to fat and cholesterol metabolism. Therefore, we speculate that ACAT2, as an important element involved in cholesterol metabolism, may become a potential molecular marker for the mechanism of pig intramuscular preadipocytes differentiation. Overexpression of ACAT2 in pig intramuscular pre-adipocytes can inhibit their differentiation, while adding ACAT2 inhibitor avasimibe can rescue the process. Knockdown of srebp2 or ldlr, which are two key genes closely related to ACAT2 and cholesterol metabolism, can inhibit pig intramuscular pre-adipocytes differentiation. Overall, our results suggest that ACAT2 is a novel negative regulator of intramuscular adipocyte differentiation through regulation of pparγ, cebpα signaling and srebp2/ldlr signaling involved in cholesterol metabolism.
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影响因子：
11.1
作者：
Krahmer, Natalie;Farese, Robert V., Jr.;Walther, Tobias C.
通讯作者：
Walther, Tobias C.
影响因子：
5.6
作者：
Han H;Wei W;Chu W;Liu K;Tian Y;Jiang Z;Chen J
通讯作者：
Chen J
DOI：
10.1016/j.jsbmb.2014.09.008
发表时间：
2015-07
期刊：
The Journal of steroid biochemistry and molecular biology
影响因子：
--
作者：
Rogers MA;Liu J;Song BL;Li BL;Chang CC;Chang TY
通讯作者：
Chang TY
影响因子：
3.3
作者：
Strieder-Barboza, Clarissa;Baker, Nicki A.;O'Rourke, Robert W.
通讯作者：
O'Rourke, Robert W.
影响因子：
4.6
作者：
Chu W;Wei W;Han H;Gao Y;Liu K;Tian Y;Jiang Z;Zhang L;Chen J
通讯作者：
Chen J