Journal of Integrative Agriculture ›› 2026, Vol. 25 ›› Issue (9): 3786-3799.DOI: 10.1016/j.jia.2025.09.006

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MFAP5通过促进脂肪细胞祖细胞向成纤维细胞谱系转变 增强仔猪抗寒性

  

  • 收稿日期:2025-02-17 修回日期:2025-09-04 接受日期:2025-08-01 出版日期:2026-09-20 发布日期:2026-08-10

MFAP5 enhances the cold resistance of piglets by promoting the transition of adipocyte progenitor cells to fibroblast lineage

Xiangfei Ma1, Mengting Li1, Shengda Qiu1, Di Liu2, Hong Ma2, Wei Wei1, Lifan Zhang1, Zan Huang1#, Jie Chen1#   

  1. 1 College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China

    2 Institute of Animal Husbandry, Heilongjiang Academy of Agricultural Sciences, Harbin 150086, China

  • Received:2025-02-17 Revised:2025-09-04 Accepted:2025-08-01 Online:2026-09-20 Published:2026-08-10
  • About author:Xiangfei Ma, E-mail: 2021205002@stu.njau.edu.cn; #Correspondence Jie Chen, E-mail: jiechen@njau.edu.cn; Zan Huang, E-mail: huangzan@njau.edu.cn
  • Supported by:

    This work was supported by grants from the Joint Funds of the National Natural Science Foundation of China (U20A2052), the National Natural Science Foundation of China (32372853, 32170847), the Jiangsu Agriculture Science and Technology Innovation Fund, China (CX(23)3137). 

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摘要：

猪缺乏典型的棕色脂肪组织，但有研究表明猪脂肪细胞具有不依赖UCP1产热的能力，然而目前对这些产热脂肪细胞的发育过程和调控机制仍然缺乏了解。本研究探究了二花脸仔猪背部皮下脂肪组织在冷刺激下的适应性反应机制，重点关注纤维/脂肪生成祖细胞（FAPs）的分化命运转变及其调控分子微纤维相关蛋白5（MFAP5）的作用，揭示了冷刺激条件下脂肪组织纤维化与产热功能的关联。本文以4对体重相近的6-8周龄雄性全同胞二花脸仔猪为试验材料，将全同胞二花脸仔猪随机分为室温组（28±0.5℃）和冷刺激组（11±0.5℃）进行30天试验。采集10个部位脂肪组织进行分析，发现背部皮下脂肪组织在冷刺激下表现出显著的产热潜力，同时观察到背部皮下脂肪组织发生组织结构重塑。综合分析背部皮下脂肪组织转录组测序和单细胞测序数据，发现冷刺激促进FAPs向非脂肪成纤维细胞分化，且MFAP5是冷刺激背部皮下脂肪组织可塑性的潜在调节因子。体外细胞试验证实，过表达MFAP5或添加MFAP5条件培养基抑制了前脂肪细胞分化为成熟脂肪细胞，促进其向非脂肪成纤维细胞分化，并显著增强非脂肪成纤维化细胞的线粒体生物合成。进一步研究表明，MFAP5主要通过Hippo-YAP1信号通路发挥作用。综上所述，本研究发现冷刺激通过上调二花脸仔猪背部皮下脂肪组织中MFAP5表达，激活Hippo-YAP1信号通路，促使FAPs分化为非脂肪成纤维细胞，进而抑制脂肪生成并促进脂肪组织纤维化和产热适应。这一发现揭示了MFAP5作为冷适应调控因子的新功能，为理解哺乳动物脂肪组织可塑性提供了新视角。

Abstract:

Although pigs lack classical brown adipose tissue, several studies have demonstrated that porcine adipocytes possess the capacity to undergo thermogenesis through UCP1-independent mechanisms.  However, the developmental processes and regulatory mechanisms underlying these thermogenic adipocytes remain poorly characterized.  Here, we found that dorsal subcutaneous adipose tissues (subWATs) in pigs exhibits significant thermogenic potential under cold stress.  Notably, we observed substantial cold-induced structural remodeling in dorsal subWATs, characterized by increased fibrotic deposition.  An integrated analysis of snRNA-seq and RNA-seq data on dorsal subWATs identified MFAP5, which encodes a microfibril-associated glycoprotein in the extracellular matrix, as a potential regulator of the cold-induced plasticity of dorsal subWATs.  Both MFAP5 overexpression and MFAP5-conditioned medium (MFAP5-CM) not only inhibited preadipocyte differentiation into adipocytes but also promoted their commitment to non-adipogenic fibrogenic lineages.  Furthermore, MFAP5 treatments significantly enhanced the mitochondrial biogenesis of these fibrogenic cells. Mechanistic investigations showed that these phenotypic alterations are predominantly mediated through the Hippo signaling pathway.  In summary, our findings elucidate the pivotal role of MFAP5 in regulating adipocyte development following cold exposure, thus providing crucial insights into the molecular mechanisms underlying porcine adaptation to cold stress.

Key words: piglets , cold adaptation ,  cell fate ,  microfibril associated protein 5