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

Xiaoli Guo; Qianqian Zhou; Jiaming Jin; Fangren Lan; Chaoliang Wen; Junying Li; Ning Yang; Congjiao Sun

doi:10.1186/s40104-023-00910-8

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

J Anim Sci Biotechnol. 2023 Aug 12;14(1):108. doi: 10.1186/s40104-023-00910-8.

Authors

Xiaoli Guo¹, Qianqian Zhou¹, Jiaming Jin¹, Fangren Lan¹, Chaoliang Wen¹, Junying Li¹, Ning Yang², Congjiao Sun³

Affiliations

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, Beijing, 100193, China.
² National Engineering Laboratory for Animal Breeding and Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, China Agricultural University, Beijing, 100193, China. nyang@cau.edu.cn.
³ National Engineering Laboratory for Animal Breeding and Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, China Agricultural University, Beijing, 100193, China. cjsun@cau.edu.cn.

Abstract

Background: Hepatic 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.

Methods: Ninety 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.

Results: The 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.

Conclusions: In 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.

Keywords: Acetylation; Cholesterol metabolism; Hepatic steatosis; Laying hens; Multiomics.

Abstract

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