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

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.

从遗传力到肠菌力：概念及研究进展

遗传力是数量遗传学中衡量性状遗传变异的重要参数之一,对动植物遗传育种、医学和进化生物学均具有重要意义。自1918年Fisher提出方差组分剖分思想后,遗传力的分析模型和估计方法不断迭代更新。近年来,一些研究者在研究肠道微生物与宿主表型关系的热点问题中,引入类似于遗传力的概念和估计方法,系统评估动物机体性状表现受肠道微生物因素的影响程度,本文将这一参数(microbiability,m2)译为"肠菌力"。文章简要介绍了遗传力估计的发展历程,概述了肠道菌群与宿主基因组的复杂关系,重点阐释了肠菌力的概念和估计方法,以期为肠道微生物组塑造宿主表型变异的研究提供一定的借鉴和参考。

Detrimental effects of excessive fatty acid secretion on female sperm storage in chickens

Background:Female sperm storage(FSS),the maintenance of sperm inside the female reproductive tract for an extended period of time,is pervasive among organisms with internal fertilization.Because FSS enables asynchronous mating and fertilization,it could be extremely important to reproduction.However,the physiological mechanisms underlying prolonged preservation and maintenance are poorly understood.Here,we used chicken,a typical oviparous animal,to determine the mechanisms ensuring sperm functionality in sperm storage tubules(SSTs).Results:We performed an insemination experiment on over two thousand hens at two periods,and found that the FSS capabilities varied widely among individuals.Except for the differences in the SST density between the two groups with distinct FSS abilities,we quantitatively profiled small-molecule metabolites derived from SST cells,and identified 28 metabolites with differential expression.In particular,high levels of lipids,fatty acids and lipid peroxidation product were observed in hens with low FSS capability.Pathway analysis showed that these differential metabolites were significantly enriched in the biosynthesis of unsaturated fatty acids.Moreover,we detected the total antioxidant capacity and lipid peroxidation level of SSTs,and found that chickens with a lower FSS ability had a significantly higher content of lipid peroxidation end-product,which was 2.4-fold greater than chickens with a higher FSS capability,and no significant difference was found in the total antioxidant capacity between these two groups.Conclusions:Our findings reveal that the long-term storage of sperm and the maintenance of their function in the female reproductive tract require an adequate microenvironment.The superabundance of fatty acids secreted by SST cells had detrimental effects on sperm storage in the female reproductive tract.Lipid peroxidation produces toxic biological substances that may cause irreversible damage to resident spermatozoa,resulting in short-term sperm retention and decreased fertility.Our findings provide new avenues for studying sperm storage and sustaining fertility.

Genetic basis of negative heterosis for growth traits in chickens revealed by genome-wide gene expression pattern analysis

Background:Heterosis is an important biological phenomenon that has been extensively utilized in agricultural breeding.However,negative heterosis is also pervasively observed in nature,which can cause unfavorable impacts on production performance.Compared with systematic studies of positive heterosis,the phenomenon of negative heterosis has been largely ignored in genetic studies and breeding programs,and the genetic mechanism of this phenomenon has not been thoroughly elucidated to date.Here,we used chickens,the most common agricultural animals worldwide,to determine the genetic and molecular mechanisms of negative heterosis.Results:We performed reciprocal crossing experiments with two distinct chicken lines and found that the body weight presented widely negative heterosis in the early growth of chickens.Negative heterosis of carcass traits was more common than positive heterosis,especially breast muscle mass,which was over−40%in reciprocal progenies.Genome-wide gene expression pattern analyses of breast muscle tissues revealed that nonadditivity,including dominance and overdominace,was the major gene inheritance pattern.Nonadditive genes,including a substantial number of genes encoding ATPase and NADH dehydrogenase,accounted for more than 68%of differentially expressed genes in reciprocal crosses(4257 of 5587 and 3617 of 5243,respectively).Moreover,nonadditive genes were significantly associated with the biological process of oxidative phosphorylation,which is the major metabolic pathway for energy release and animal growth and development.The detection of ATP content and ATPase activity for purebred and crossbred progenies further confirmed that chickens with lower muscle yield had lower ATP concentrations but higher hydrolysis activity,which supported the important role of oxidative phosphorylation in negative heterosis for growth traits in chickens.Conclusions:These findings revealed that nonadditive genes and their related oxidative phosphorylation were the major genetic and molecular factors in the negative heterosis of growth in chickens,which would be beneficial to future breeding strategies.