南方医科大学学报

南方医科大学学报 ›› 2024, Vol. 44 ›› Issue (3): 499-506.doi: 10.12122/j.issn.1673-4254.2024.03.11

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激活α7nAchR促进肥胖小鼠的脂肪稳态和米色脂肪生成及产热作用

包汉生，王苏童，吕穆杰，王永成，姜 萍，李 晓   

  1. 山东中医药大学，山东 济南 250355；山东中医药大学附属医院，山东 济南 250014
  • 出版日期:2024-03-20 发布日期:2024-04-02

Activation of α7 nAChR improves white fat homeostasis and promotes beige adipogenesis and thermogenesis in obese mice

BAO Hansheng, WANG Sutong, LÜ Mujie, WANG Yongcheng, JIANG Ping, LI Xiao   

  1. Shandong University of Traditional Chinese Medicine, Jinan 250355, China; Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, China
  • Online:2024-03-20 Published:2024-04-02

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摘要： 目的 观察肥胖小鼠脂肪组织形态学改变以及脂代谢、炎症等相关指标的异常表现，探索激活α7烟碱型乙酰胆碱受体（α7 nAchR）促进肥胖机体白色脂肪米色化产热的作用机制。方法 取诱导成肥胖小鼠40只和10只低脂进食小鼠，分为空白组、高脂组、模型组、激动剂组、抑制剂组（10只/组）。苏木素-伊红（HE）染色观察小鼠附睾白色脂肪组织，评估细胞数量、大小及形态。ELISA检测白色脂肪组织肿瘤坏死因子（TNF-α）、白细胞介素-1（IL1β）、白细胞介素10（IL10）、转化生长因子-β（TGF-β）表达水平。qRT-PCR检测白色脂肪一氧化氮合酶（iNOS）、精氨酸酶1（Arg1）mRNA。PCR检测解偶联蛋白（UCP-1）、PR结构域蛋白16（PRDM-16）、线粒体生成的关键调节因子（PGC-1α）mRNA水平。Western blot检测白色脂肪核转录因子P65（NF-κBP65）、磷酸化蛋白酪氨基酸激酶2（p-JAK2）、磷酸化传导及转录激活因子3（p-STAT3）表达水平。结果 与空白组比较，高脂组体质量明显增加（P<0.01），白色脂肪组织中出现较多脂肪空泡，脂滴明显增大，iNOS mRNA及TNF-α、IL-1β水平升高（P<0.01），而Arg-1 mRNA及IL-10、TGF-β水平降低（P<0.01）；而与模型组相比，药物干预的3组体质量均有所减轻（P<0.05），白色脂肪中脂滴缩小。激动剂组白色脂肪中PRDM-16、PGC-1α、UCP-1 mRNA下降最为明显。而激动剂组TNF-α、IL-1β水平降低（P<0.05，P<0.01），IL-10、TGF-β水平升高（P<0.01），M1/M2巨噬细胞比值降低。结论 激活α7 nAchR后可以改善应用β3受体激动剂产生的白色脂肪组织稳态受损，促进白色脂肪中M1型巨噬细胞向M2型巨噬细胞转化减轻白色脂肪炎症反应，促进白色脂肪组织米色化，提高米色化产热效能。

关键词: 肥胖；白色脂肪组织；α7 nAchR；产热；炎症反应

Abstract: Objective To investigate the effects of α7 nicotinic acetylcholine receptor (nAChR) agonist on β3-adrenoceptor agonist-induced impairment of white fat homeostasis and beige adipose formation and heat production in obese mice. Methods Forty obese C57BL/6J mice were randomized into high-fat feeding group, β3-adrenoceptor agonist-treated model group, α7 nAChR agonist group, and α7 nAChR inhibitor group (n=10), with another 10 mice with normal feeding as the blank control group. White adipose tissue from the epididymis of the mice were sampled for HE staining of the adipocytes. The expression levels of TNF-α, IL-1β, IL-10 and TGF-β in the white adipose tissue were determined by ELISA, and the mRNA levels of iNOS, Arg1, UCP-1, PRDM-16 and PGC-1α were detected using RT-qPCR. Western blotting was performed to detect the expression levels of NF-κB P65, p-JAK2, p-STAT3 in the white adipose tissue. Results Compared with those in the blank control group, the mice with high- fat feeding showed significantly increased body weight, more fat vacuoles in the white adipose tissue, increased volume of lipid droplets in the adipocytes, upregulated iNOS mRNA expression and protein expression of TNF-α and IL-1β, and lowered expression of Arg-1 mRNA and IL-10 and TGF-β proteins (P<0.01). Treatment with α7 nAChR significantly reduced mRNA levels of PRDM-16, PGC-1α and UCP-1, lowered TNF-α and IL-1β expressions, increased IL-10 and TGF-β expressions, and reduced M1/M2 macrophage ratio in the white adipose tissues (P<0.05 or 0.01). Conclusion Activation of α7 nAchR improves white adipose tissue homeostasis impairment induced by β3 agonist, promotes transformation of M1 to M2 macrophages, reduces inflammatory response in white adipose tissue, and promote beige adipogenesis and thermogenesis in obese mice.

Key words: obesity; white adipose tissue; α7 nicotinic acetylcholine receptor; thermogenesis; inflammatory response