中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (6): 1424-1430.doi: 10.12307/2026.554

• 组织构建实验造模 experimental modeling in tissue construction • 上一篇    下一篇

无毛基因突变促进无毛小鼠白色脂肪组织褐变的作用机制

朱奎成1，杜春燕1，章金涛2   

  1. 郑州大学，1实验动物中心，2河南省医药科学研究院，河南省郑州市  450052
  • 收稿日期:2024-12-10 接受日期:2025-02-13 出版日期:2026-02-28 发布日期:2025-07-15
  • 通讯作者: 章金涛，博士，教授，郑州大学河南省医药科学研究院，河南省郑州市 450052
  • 作者简介:朱奎成，男，1975年生，四川省广元市人，汉族，博士，副教授，主要从事组织再生研究。
  • 基金资助:
    国家自然科学基金项目(31372270)，项目负责人：章金涛

Mechanism by which hairless gene mutation promotes white adipose tissue browning in hairless mice

Zhu Kuicheng1, Du Chunyan1, Zhang Jintao2   

  1. 1Laboratory Animal Center, 2Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450052, Henan Province, China
  • Received:2024-12-10 Accepted:2025-02-13 Online:2026-02-28 Published:2025-07-15
  • Contact: Zhang Jintao, PhD, Professor, Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450052, Henan Province, China
  • About author:Zhu Kuicheng, PhD, Associate professor, Laboratory Animal Center, Zhengzhou University, Zhengzhou 450052, Henan Province, China
  • Supported by:
    the National Natural Science Foundation of China, No. 31372270 (to ZJT)

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摘要：


文题释义：
脂肪组织褐变：由于环境或遗传改变，白色脂肪转化成棕色脂肪的过程。白色脂肪组织主要以三酰甘油的形式储存能量，棕色脂肪组织可以产热，将储存的能量转化为热量。促进脂肪组织棕色化(即褐变)，已成为治疗肥胖的有效策略。
无毛基因：是一个多效基因，无毛基因编码的蛋白是甲状腺激素受体的辅阻遏因子，无毛基因突变可引起人和动物脱发、早衰、免疫低下和脂质代谢紊乱等生理学改变。

背景：白色脂肪存储能量，棕色脂肪消耗能量。白色脂肪褐变是对抗肥胖和代谢紊乱的有效策略，但驱动这一过程的机制尚不清楚。
目的：揭示无毛基因突变导致白色脂肪褐变的分子机制。
方法：选取10周龄雄性豫医无毛小鼠和同窝出生的野生型小鼠各10只，记录小鼠体质量、采食量和腹股沟白色脂肪组织质量；ELISA法检测血清瘦素和脂联素水平；葡萄糖耐量实验评估糖代谢功能；胰岛素耐量实验分析胰岛素敏感性；苏木精-伊红染色观察腹股沟白色脂肪组织的形态学变化；实时荧光定量PCR和免疫染色分析腹股沟白色脂肪组织褐变相关基因和蛋白表达。
结果与结论：①与野生型小鼠相比，豫医无毛小鼠褐色脂肪含量增加，并最终增加对葡萄糖耐受性和胰岛素敏感性；无毛基因突变降低了小鼠体质量和腹股沟脂肪质量，但采食量与野生型小鼠比较无明显变化，表明体质量和脂肪质量减轻并非因食物摄入减少；②苏木精-伊红染色显示豫医无毛小鼠腹股沟白色脂肪组织的脂肪细胞发生褐变，变小、变圆并伴有多室细胞出现；③腹股沟白色脂肪组织中脂肪细胞过氧化物酶体增殖物激活受体γ共激活因子1α表达升高，激活甲状腺激素受体α，驱动解偶联蛋白1、线粒体生物发生基因核呼吸因子1和线粒体转录因子A表达，促进脂肪细胞褐变。因此，无毛基因突变激活了过氧化物酶体增殖物激活受体γ共激活因子1α/甲状腺激素受体α/解偶联蛋白1信号通路，小鼠棕色脂肪含量增加，从而促进能量消耗和产热，抑制肥胖。
https://orcid.org/0000-0001-8665-7297(朱奎成)

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

关键词: 无毛基因, 脂肪细胞褐变, 过氧化物酶体增殖物激活受体γ共激活因子1α(PGC-1α)/甲状腺激素受体α(TRα)/解耦联蛋白1(UCP1)信号通路, 解偶联蛋白1, 肥胖, 豫医无毛小鼠

Abstract: BACKGROUND: In mammals, white adipose tissue stores energy, whereas brown adipose tissue dissipates energy. Conversion from White to brown/beige adipocytes is a potential therapeutic strategy to fight obesity, but the molecular mechanisms that drive this process is unclear.  
OBJECTIVE: To reveal the potential relationship between Hr mutation and adipocyte browning.
METHODS: Ten 10-week-old male Yuyi hairless mice and 10 littermate wild-type controls were selected and changes in food intake, body mass and inguinal white adipose tissue mass were recorded. Serum levels of leptin and adiponectin were estimated by ELISA. Glucose tolerance test was used to assess glucose metabolic function and insulin tolerance test was performed to analyze insulin sensitivity. Hematoxylin-eosin staining was performed to observe pathological changes of inguinal white adipose tissue in mice. Real-time fluorescence quantitative PCR and immunofluorescent staining were performed to analyze the expression of genes and proteins associated with browning of white adipose tissue in the groin.
RESULTS AND CONCLUSION: (1) Compared with wild-type mice, Yuyi hairless mice had increased brown fat content and ultimately increased glucose tolerance and insulin sensitivity. Hr mutation reduced body mass and inguinal adipose mass in mice, but food intake did not change significantly compared with wild-type mice, suggesting that there was a reduction in body mass and adipose mass but not in food intake. (2) Hematoxylin-eosin staining results showed browning of adipocytes in the inguinal white adipose tissue of Yuyi hairless mice, which became smaller, rounder and accompanied by the appearance of multilocular cells. (3) There was increased level of peroxisome proliferator-activated receptor γ coactivator 1α and activation of thyroid hormone receptor α, uncoupling protein 1, and the mitochondria-shaping genes (nuclear respiratory factor 1 and mitochondrial transcription factor A), thereby promoting browning of adipocytes. Thus, Hr mutation activates the peroxisome proliferator-activated receptor γ coactivator 1α/thyroid hormone receptorα/uncoupling protein 1 signaling pathway and increases brown adipose content in mice, thereby promoting energy expenditure and thermogenesis and inhibiting obesity.

Key words: hairless gene, white adipocyte browning, peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α)/thyroid hormone receptor α (TRα)/uncoupling protein 1 signaling pathway (UCP1) signaling pathway, uncoupling protein 1, obesity, Yuyi hairless mouse

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