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Journal of Integrative Agriculture  2023, Vol. 22 Issue (3): 853-863    DOI: 10.1016/j.jia.2022.08.071
Animal Science · Veterinary Medicine Advanced Online Publication | Current Issue | Archive | Adv Search |
TIMP2 promotes intramuscular fat deposition by regulating the extracellular matrix in chicken

CUI Huan-xian*, LUO Na*, GUO Li-ping, LIU Lu, XING Si-yuan, ZHAO Gui-ping#, WEN Jie#

State Key Laboratory of Animal Nutrition/Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, P.R.China
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摘要  肌细胞与肌内脂肪细胞之间的相互作用是一个热门的科学论题。本研究采用共培养体系,通过肌细胞和脂肪细胞的相互作用来研究对鸡肌肉组织的肌内脂肪沉积的调控,并找出重要的中间调节因子。本研究使用7日龄的北京油鸡进行肌内脂肪细胞和肌卫星细胞的提取,将肌内脂肪细胞与肌卫星细胞进行共培养,收取共培养体系和单独培养的肌内脂肪细胞、单独培养的肌卫星细胞的细胞培养液进行蛋白组学的测序。同时,在数据库下载不同日龄的鸡胸肌和腹脂组织的表达谱及高肌内脂肪和低肌内脂肪的转录组数据进行验证。我们的蛋白质组学数据显示,在共培养体系的培养液中,金属蛋白酶组织抑制因子2 (tissue inhibitor of metalloproteases 2, TIMP2)的蛋白表达显著增加,共培养的肌内脂肪细胞中脂滴含量较多。此外,TIMP2在肌内脂肪含量高的个体肌肉组织中显著上调(P<0.01)。基因加权共表达网络分析显示,TIMP2主要参与细胞外基质受体相互作用信号通路,其表达与甘油三酯、肌内脂肪、C14:0、C14:1、C16:0、C16:1、C18:1n9C水平显著相关。此外,TIMP2与多种脂质代谢相关的代表性基因(如ADIPOQSCDELOVL5ELOVL7LPL)以及某些参与细胞外基质受体相互作用的基因(如COL1A2COL4A2COL5A1COL6A1COL6A3)共表达,在肌内脂肪含量高的个体肌肉组织中也显著或极显著上调(P < 0.05或P < 0.01)。我们的研究结果表明,TIMP2通过细胞外基质受体相互作用信号通路促进肌内脂肪沉积。本研究是第一次对TIMP2在脂质沉积方面的报道,本研究结果为鸡脂质沉积的分子机制以及肌内脂肪细胞与肌卫星细胞之间的相互作用提供了新的研究思路,为今后禽肉的优质生产提供了理论依据。


The interaction between myocytes and intramuscular adipocytes is a hot scientific topic.  Using a co-culture system, this study aims to investigate the regulation of intramuscular fat deposition in chicken muscle tissue through the interaction between myocyte and adipocyte and identify important intermediary regulatory factors.  Our proteomics data showed that the protein expression of tissue inhibitor of metalloproteinases 2 (TIMP2) increased significantly in the culture medium of the co-culture system, and the content of lipid droplets was more in the co-culture intramuscular adipocytes.  In addition, TIMP2 was significantly upregulated (P<0.01) in muscle tissue of individuals with high intramuscular fat content.  Weighted gene co-expression network analysis revealed that TIMP2 was mainly involved in the extracellular matrix receptor interaction signaling pathway and its expression was significantly correlated with triglyceride, intramuscular fat, C14:0, C14:1, C16:0, C16:1, and C18:1n9C levels.  Additionally, TIMP2 was co-expressed with various representative genes related to lipid metabolism (such as ADIPOQ, SCD, ELOVL5, ELOVL7, and LPL), as well as certain genes involved in extracellular matrix receptor interaction (such as COL1A2, COL4A2, COL5A1, COL6A1, and COL6A3), which are also significantly upregulated (P<0.05 or P<0.01) in muscle tissue of individuals with high intramuscular fat content.  Our findings reveal that TIMP2 promotes intramuscular fat deposition in muscle tissue through the extracellular matrix receptor interaction signaling pathway.

Keywords:  TIMP2       ECM        intramuscular adipocytes        muscle satellite cells        chicken  
Received: 28 October 2021   Accepted: 28 January 2022
Fund: This research was funded by the grants from the National Natural Science Foundation of China (31872340), the State Key Laboratory of Animal Nutrition (2004DA125184G2109), the Agricultural Science and Technology Innovation Program of Chinese Academy of Agricultural Sciences (ASTIP-IAS04), and the earmarked fund for China Agriculture Research System (CARS-41).
About author:  Cui Huan-xian, E-mail:; LUO Na, E-mail:; #Correspondence WEN Jie, E-mail:; ZHAO Gui-ping, E-mail: * These authors contributed equally to this study.

Cite this article: 

CUI Huan-xian, LUO Na, GUO Li-ping, LIU Lu, XING Si-yuan, ZHAO Gui-ping, WEN Jie. 2023. TIMP2 promotes intramuscular fat deposition by regulating the extracellular matrix in chicken. Journal of Integrative Agriculture, 22(3): 853-863.

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