Quercetin improves hepatic lipid accumulation by up-regulating lipolysis and lipophagy pathways
10.16016/j.2097-0927.202401003
- VernacularTitle:槲皮素通过上调脂解和脂噬途径改善肝细胞脂质蓄积
- Author:
Yan ZHANG
1
;
Yilin YANG
;
Jiaqi YUAN
;
Mantian MI
;
Yu QIN
Author Information
1. 400038 重庆,陆军军医大学(第三军医大学)军事预防医学系营养与食品安全研究中心,重庆市医学营养研究中心,重庆市营养与健康重点实验室
- Keywords:
quercetin;
hepatic lipid accumulation;
lipolysis;
lipophagy
- From:
Journal of Army Medical University
2024;46(20):2301-2312
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect and mechanism of quercetin (QUE)in improving lipid accumulation in hepatocytes by regulating lipolysis and lipophagy pathway.Methods The human hepatocyte cell line 5 (HHL-5)was induced by palmitic acid (PA)to establish a steatogenic hepatocyte model.Quercetin at different concentrations (5,10,20 and 40 μmol/L)has been utilized to interfere with HHL-5 cells for 24 h,and the experiment was divided into six groups:control group,PA group,PA+QUE5 group,PA+QUE10 group,PA+QUE20 groupand PA+QUE40 group.In order to determine the influence of lipophagy on QUE effect,3-methyladenine (3-MA)was used to block autophagy,and HHL-5 cells were divided into the control,PA,PA+QUE40,3-MA,PA+3-MA and PA+3-MA+QUE40 groups.The contents of triglyceride (TG),accumulations of lipid droplets,expression of lipolysis and lipophagy related molecules,and degree of co-localization,and expression level of substrate of autophagy P62 were detected in above 2 types of experimental groups.Results Compared with the control group,the TG content and the lipid accumulation were significantly increased,the protein levels,average fluorescence intensities and colocalization degree of lipolysis related molecules adipose triglycerides lipase(ATGL)and comparative gene identification-58(CGI58),and lipophagy related molecules Ras-related protein 7(RAB7)and microtubule-associated protein 1 light chain 3 beta (LC3β)were significantly decreased,while the expression of P62 was enhanced in HHL-5 cells in the PA group (all P<0.05 ).Compared with the PA group,the triglyceride content and the degree of lipid accumulation in the PA+QUE40 group were significantly decreased,and the protein expression level,average fluorescence intensity and co-localization degree of lipolysis and lipophagy related molecules were significantly increased,while P62 was significantly decreased (P<0.05).When 3-MA was added to the steatogenic hepatocytes to inhibit autophagy,the improvement effect of QUE on lipid accumulation and the regulation of lipolysis and liphagy related molecules in steatogenic hepatocytes were neutralized.Conclusion QUE alleviates lipid accumulation in HHL-5 cells by promoting the expression and interaction of molecules related to lipolysis and lipophagy pathways.However,these effects can be weakened by the autophagy inhibitor 3-MA.