Hepatic steatosis is associated with dysregulated cholesterol metabolism and altered protein acetylation dynamics in chickens

Journal of Animal Science and Biotechnology

Research

Qianqian Zhou¹  Congjiao Sun¹  Junying Li¹  Fangren Lan¹  Ning Yang¹  Jiaming Jin¹  Xiaoli Guo¹  Chaoliang Wen¹ 

[1] National Engineering Laboratory for Animal Breeding and Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, China Agricultural University, 100193, Beijing, China;

关键词: Acetylation;    Cholesterol metabolism;    Hepatic steatosis;    Laying hens;    Multiomics;   

DOI  :  10.1186/s40104-023-00910-8

 received in 2023-04-23, accepted in 2023-06-28,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundHepatic steatosis is a prevalent manifestation of fatty liver, that has detrimental effect on the health and productivity of laying hens, resulting in economic losses to the poultry industry. Here, we aimed to systematically investigate the genetic regulatory mechanisms of hepatic steatosis in laying hens.MethodsNinety individuals with the most prominent characteristics were selected from 686 laying hens according to the accumulation of lipid droplets in the liver, and were graded into three groups, including the control, mild hepatic steatosis and severe hepatic steatosis groups. A combination of transcriptome, proteome, acetylome and lipidome analyses, along with bioinformatics analysis were used to screen the key biological processes, modifications and lipids associated with hepatic steatosis.ResultsThe rationality of the hepatic steatosis grouping was verified through liver biochemical assays and RNA-seq. Hepatic steatosis was characterized by increased lipid deposition and multiple metabolic abnormalities. Integration of proteome and acetylome revealed that differentially expressed proteins (DEPs) interacted with differentially acetylated proteins (DAPs) and were involved in maintaining the metabolic balance in the liver. Acetylation alterations mainly occurred in the progression from mild to severe hepatic steatosis, i.e., the enzymes in the fatty acid oxidation and bile acid synthesis pathways were significantly less acetylated in severe hepatic steatosis group than that in mild group (P < 0.05). Lipidomics detected a variety of sphingolipids (SPs) and glycerophospholipids (GPs) were negatively correlated with hepatic steatosis (r ≤ −0.5, P < 0.05). Furthermore, the severity of hepatic steatosis was associated with a decrease in cholesterol and bile acid synthesis and an increase in exogenous cholesterol transport.ConclusionsIn addition to acquiring a global and thorough picture of hepatic steatosis in laying hens, we were able to reveal the role of acetylation in hepatic steatosis and depict the changes in hepatic cholesterol metabolism. The findings provides a wealth of information to facilitate a deeper understanding of the pathophysiology of fatty liver and contributes to the development of therapeutic strategies.

【 授权许可】

CC BY   
© Chinese Association of Animal Science and Veterinary Medicine 2023

【 图 表 】

Fig. 3

Fig. 1

Fig. 2

Fig. 1

Fig. 4

Fig. 5