| Fatty liver is a metabolic disease caused by the negative energy balance of dairy cows during the perinatal period,which seriously threatens the health and milk production of the postpartum,which not only shortens the life of the cow,but also increases the economic loss of the enterprise.Fatty liver in dairy cows has the same characteristics as non-alcoholic fatty liver in humans: the accumulation of fat in the liver.Advances in proteomics technology have promoted the discovery of clinically important protein biomarkers.Recent studies have shown that during the development of non-alcoholic fatty liver in humans,and many proteins have been identified to play important metabolic regulation of liver function.However,there is no clear study on the occurrence of fatty liver in dairy cows.Previous studies have shown that lysine acetylation modification plays an important role in material metabolism and energy metabolism.The liver,as an important metabolic organ,is affected by acetylation in most of its metabolic processes.There are not many studies on lysine acetylation modification in the pathogenesis of fatty liver in dairy cows.Based on the preliminary screening of serum biochemical indexes and the diagnosis of liver biopsy,the normal liver(recorded as norm,fat content = 6.26% ± 5.23%,n = 6)and severe fatty liver(recorded as FL,fat content = 86.75% ± 4.83%,n = 8)were collected in the experiment.Using TMT and HPLC-MS to analyze proteome and acetylated modified group,we set up three biological repeats respectively,From the omics level,we learned about the biological changes in the liver when fatty livers occur in dairy cows during the perinatal period.This provided us with an in-depth understanding of the pathogenesis of fatty livers.In this study,proteomics and acetylomics were used to screen out the important protein regulatory targets of fatty liver in dairy cows as biomarkers,which will provide a strongscientific basis for the diagnosis of fatty liver in production practice.The results showed that:(1)In this study,the acetylation group analysis of liver tissues in perinatal dairy cows found that 36.7% of the total acetylated proteins were located in mitochondria and 46.6% of acetylated sites related to mitochondrial proteins.Among them,74.1% of mitochondrial proteins and 84.5% of acetylated sites located in mitochondria were significantly up-regulated.It shows that impaired mitochondrial function of liver cells is an important intrinsic cause of fatty liver.Among them,the acetylation modification of mitochondrial protein is an important reason for mitochondrial dysfunction,that is,acetylation modification is an important means of mitochondrial function regulation.(2)In this study,the proteome analysis of dairy cow livers in perinatal period revealed important pathways related to the regulation of fatty liver pathogenesis,in which the retinol metabolic pathway was significantly inhibited during the pathogenesis of fatty liver.(3)Through the preliminary screening of the combined data analysis of proteomics and acetylomics of the mixed samples and the secondary screening of the proteomics data of the single sample,it is found that the expression level of AOX1 and ALDH1A1 has a good negative correlation with the severity of fatty liver,which is an important regulatory target protein in the pathogenesis of fatty liver.(4)In the analysis of acetylation group,mitochondrial protein HADHA,ACAT1 and EHHADH showed significant differences in the acetylation level in multiple lipid metabolism related pathways,and they highly interacted with other proteins,which may be an important regulator of acetylation modification in the process of fatty liver development in dairy cows,and may become the therapeutic target of human NAFLD.This study provides an important theoretical guidance for us to further understand the metabolic disorders of perinatal cows.At the same time,it provides potential important drug targets for further screening,treatment and early warning of fatty liver in dairy cows,and has important guiding value for the future breeding of anti fatty liver cows. |
