Role of Perilipin 2 in microvesicular hepatic steatosis induced by CGI-58 specific knockout in mice
10.16016/j.2097-0927.202405103
- VernacularTitle:Perilipin 2在小鼠肝脏CGI-58特异性敲除所致肝脏微泡型脂肪变性中的作用
- Author:
Yixin ZHANG
1
,
2
,
3
;
Jie LI
;
Xiaoqin WAN
;
Xiaoqing JIANG
;
Jianghui CHEN
;
Fang DENG
;
Mindian LI
;
Qian ZHANG
;
Xinyu BAO
;
Zhihui ZHANG
Author Information
1. 400038 重庆,陆军军医大学(第三军医大学)第一附属医院心血管内科代谢生物钟与心血管疾病中心
2. 400038 重庆,陆军军医大学(第三军医大学)第一附属医院老年心脑血管疾病教育部重点实验室
3. 400016 重庆,重庆医科大学基础医学院
- Keywords:
microvesicular hepatic steatosis;
Perilipin 2;
CGI-58;
Chanarin-Dorfman syndrome;
lipid droplet
- From:
Journal of Army Medical University
2024;46(15):1701-1712
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore whether hepatocyte Perilipin-2(Plin2)is involved in the development of fatty liver related to comparative gene identification-58(CGI-58)deficiency mice and compare the effects of Plin2 and Plin3 on lipid droplet formation and lipid accumulation.Methods Based on CGI-58Flox/Flox mice as animal model,the adeno-associated viruses targeting mouse liver,CGI-58 knockout and Plini2 knockdown were achieved by co-expression Cre protein and micro-RNA targeting Plin2(Mi-KD).Then CGI-58 deficiency mice were used as control(NC)to detect the differences in metabolic phenotype and liver pathology.AML-12 mouse hepatocytes were used as cellular model and interfered with siRNA to achieve Plin2/Plin3 knockdown in AML-12 cells.Lipid droplet formation and lipid accumulation were compared with Bodipy staining and enzyme colorimetry in basal condition or lipid-overloaded condition(OA inducement)after Plin2/Plin3 knockdown.Results Plin2 knockdown(Mi-KD)reduced PLIN2 protein level by＞99％in mouse livers.Mi-KD decreased hepatomegaly(P=0.019 5)and liver injury(P=0.000 4),while reduced the histological NAS score(P=0.000 2)and hepatic triglyceride content(P=0.016 6)in the CGI-58 deficiency female mice.Mi-KD prevented microvesicular hepatic steatosis in the CGI-58 deficient female mice.Plin3 knockdown significantly reduced the triglyceride content in basal condition of hepatocytes(P=0.001 4),and Plin2 knockdown just showed a decreased trend.Plin2 or Plin3 knockdown significantly reduced the triglyceride content separately in lipid-overloaded hepatocytes(P＜0.05).Conclusion Hepatocyte Plin2 is essential in the development of microvesicular hepatic steatosis caused by CGI-58 deficiency.Both Plin2 and Plin3 are involved in lipid droplet formation and lipid accumulation in hepatocytes,and Plin3 shows a stronger effect.
