Translatome Study Of Betaine Regulating Liver Lipid Metabolism In Mice

With the improvement of living standards,people’s demand for animal protein is getting higher and higher.The important task of animal husbandry is,on the one hand,to improve the lean rate of livestock and poultry and reduce subcutaneous fat;on the other hand,in order to ensure the quality of meat,it is necessary to accumulate appropriate fat in muscle.Therefore,lipid metabolism plays an important role in it.The liver is an important organ of fat metabolism and the main site of endogenous fat production.The level of triglyceride(TG)in liver is an important index of lipid metabolism in animals.Excessive accumulation of TG will affect the health of animals and lead to liver steatosis,which is not conducive to the development of animal husbandry.Betaine,also known as trimethylglycine,is a natural small molecular compound.More and more evidence has approved that betaine can effectively reduce the accumulation of TG in the liver.Translational regulation is considered to play a vital role in gene expression,but it is not clear whether betaine plays a role through the regulation of gene translation level.In order to investigate the regulatory effect of betaine treatment on liver lipid metabolism,high fat diet mice(HFD group,n=6)and high fat diet supplemented betaine mice model(HB group,n=6)were established in vivo,and Hep G2 hepatocytes were induced by high fat medium of oleic acid and palmitic acid(OA/PA)at cellular level.The results of both studies confirmed that betaine can alleviate the accumulation of TG in the liver.In order to systematically describe the translation map of betaine in liver lipid metabolism and screen the key genes that betaine plays a lipid-lowering role,we performed transcriptome sequencing(RNA-seq)and translatome sequencing(RNC-seq)on the livers of mice in HFD group and HB group.The results showed that:(1)1886 differentially expressed genes(DEGs)were identified by transcriptome sequencing.Gene set enrichment analysis(GSEA)showed that betaine reduced liver fat deposition by up-regulating fatty acid β oxidation,lipid oxidation and fatty acid catabolism.(2)324 DEGs were identified by translatome,and some genes related to nonalcoholic fatty liver disease and lipid metabolism were differentially expressed at the translational level,suggesting that betaine does play a lipid-lowering role by regulating the level of gene translation.(3)the joint analysis of transcriptome and translatome revealed that the gene translation rate(TR)increased significantly after betaine treatment,and 1063 differential translation rate genes(DTRGs)were identified,and DTRGs was enriched in lipid metabolic pathways such as fatty acid degradation.(4)A new functional gene GPC1 was identified,which may mediate the lipid-lowering effect of betaine in liver.To sum up,betaine can improve liver lipid metabolism.This study described the expression map of genes in the liver of mice with or without betaine treatment from the perspective of translatome and transcriptome,and deepened the understanding of the lipid-lowering effect of betaine,and identified new functional genes that regulate liver lipid metabolism.