Activation of α7 nAChR improves white fat homeostasis and promotes beige adipogenesis and thermogenesis in obese mice
10.12122/j.issn.1673-4254.2024.03.11
- VernacularTitle: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
- Author:
Hansheng BAO
1
;
Sutong WANG
;
Mujie LÜ
;
Yongcheng WANG
;
Ping JIANG
;
Xiao LI
Author Information
1. 山东中医药大学,山东 济南 250355
- Keywords:
obesity;
white adipose tissue;
α7 nicotinic acetylcholine receptor;
thermogenesis;
inflammatory response
- From:
Journal of Southern Medical University
2024;44(3):499-506
- CountryChina
- Language:Chinese
-
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.
