Background： Fatness traits in animals are important for their growth, meat quality, reproductive performance, and immunity. The liver is the principal organ of the regulation of lipid metabolism, and this study used ...Background： Fatness traits in animals are important for their growth, meat quality, reproductive performance, and immunity. The liver is the principal organ of the regulation of lipid metabolism, and this study used massive parallelized high-throughput sequencing technologies to determine the porcine liver tissue transcriptome architecture of two full-sibling Songliao black pigs harboring extremely different phenotypes of backfat thickness. Results： The total number of reads produced for each sample was in the region of 53 million, and 8,226 novel transcripts were detected. Approximately 92 genes were differentially regulated in the liver tissue, while 31 spliced transcripts and 33 primary transcripts showed significantly differential expression between pigs with higher and lower backfat thickness. Genes that were differentially expressed were involved in the metabolism of various substances, smal molecule biochemistry, and molecular transport. Conclusions： Genes involved in the regulation of iipids could play an important role in lipid and fatty acid metabolism in the liver. These results could help us understand how liver metabolism affects the backfat thickness of pigs.展开更多
Background Backfat thickness(BFT)is a vital economic trait in pigs,reflecting subcutaneous fat levels that affect meat quality and production efficiency.As a complex trait shaped by multiple genetic factors,BFT has be...Background Backfat thickness(BFT)is a vital economic trait in pigs,reflecting subcutaneous fat levels that affect meat quality and production efficiency.As a complex trait shaped by multiple genetic factors,BFT has been studied using genome-wide association studies(GWAS)and linkage analyses to locate fat-related quantitative trait loci(QTLs),but pinpointing causal variants and genes is hindered by linkage disequilibrium and limited regulatory data.This study aimed to dissect the QTLs affecting BFT on Sus scrofa chromosome 1(SSC1),elucidating regulatory variants,effector genes,and the cell types involved.Results Using whole-genome genotyping data from 3,578 pigs and phenotypic data for five BFT traits,we identified a 630.6 kb QTL on SSC1 significantly associated with these traits via GWAS and fine-mapping,pinpointing 34 candidate causal variants.Using deep convolutional neural networks to predict regulatory activity from sequence data integrated with detailed pig epigenetic profiles,we identified five SNPs potentially affecting enhancer activity in specific tissues.Notably,rs342950505(SSC1:161,123,588)influences weak enhancer activity across multiple tissues,including the brain.High-throughput chromosome conformation capture(Hi-C)analysis identified that rs342950505 interacts with eight genes.Chromatin state annotations confirmed enhancer activity at this QTL in the cerebellum.Leveraging these insights,single-cell ATAC-seq revealed a chromatin accessibility peak encompassing rs342950505 that regulates PMAIP1 expression in inhibitory neurons via enhancer-mediated mechanisms,with an adjacent peak modulating CCBE1 expression in neuroblasts and granule cells.Transcriptome-wide association studies(TWAS)confirmed PMAIP1's role in the hypothalamus,and Mendelian randomization(MR)validated PMAIP1 and CCBE1 as key brain expression quantitative trait locus(eQTL)effectors.We propose that the variant rs342950505,located within a regulatory peak,modulates PMAIP1 expression in inhibitory neurons,potentially influencing energy homeostasis via hypothalamic regulation.Similarly,CCBE1 may contribute to this process.Conclusions Our results,through systematic dissection of pleiotropic BFT-associated loci,provide a framework to elucidate regulatory mechanisms of complex traits,offering insights into polygenic control through lipid metabolism and neural signaling pathways.展开更多
Background Increased backfat thickness of sows in early gestation is negative to reproductive performance.Endometrial receptivity is an important determinant of reproductive success,but it is unclear whether the effec...Background Increased backfat thickness of sows in early gestation is negative to reproductive performance.Endometrial receptivity is an important determinant of reproductive success,but it is unclear whether the effect of sow backfat thickness on litter size is associated with endometrial receptivity and whether melatonin treatment may have benefits.The present study seeks to answer these questions through in vitro and in vivo investigations.Results Excessive lipid deposition and lower melatonin levels in the uterus are detrimental to endometrial receptivity and embryo implantation in high backfat thickness sows.In cells treated with melatonin,the MT2/PI3K/LIF axis played a role in reducing lipid accumulation in porcine endometrial epithelium cells and improved endometrial receptivity.Furthermore,we found a reduction of lipids in the uterus after eight weeks of intraperitoneal administration of melatonin to HFD mice.Notably,melatonin treatment caused a significant reduction in the deposition of endometrial collagen,an increase in the number of glands,and repair of the pinopode structure,ultimately improving endometrial receptivity,promoting embryo implantation,and increasing the number of litter size of mice.Conclusions Collectively,the finding reveals the harmful effects of high backfat thickness sows on embryo implantation and highlight the role of melatonin and the MT2/PI3K/LIF axis in improving endometrial receptivity by enhancing metabolism and reducing the levels of uterine lipids in obese animals.展开更多
The measurement of pig backfat thickness(PBFT)has to stand up to challenges with the reliability,accuracy,and convenience.Acquiring PBFT timely and precisely from a finite distance is extremely necessary to improve th...The measurement of pig backfat thickness(PBFT)has to stand up to challenges with the reliability,accuracy,and convenience.Acquiring PBFT timely and precisely from a finite distance is extremely necessary to improve the process of pig production and implement effective management.In an attempt to alleviate these problems,an online handheld terminal was designed with a new method based on ultrasonic technology for measuring PBFT during the process of pig breeding,which can overcome the difficulties encountered in other destructive means.The terminal comprised three main components:a main microcontroller unit(MCU)to measure PBFT,a RFID module to identify each pig and send data(e.g.identity,measurement time and PBFT)to a server via wireless transmission module,and an ultrasonic transducer to drive and receive signals between them.A measurement error within 0-1 mm was acquired through testing three groups of samples.Results indicated that this handheld terminal had a required accuracy and proved that the ultrasonic wave processing method can be deployed in a mobile terminal for PBFT measurement.It also provided a feasible nondestructive alternative to measure PBFT.Associated with information management software platform,this method may ultimately help pig production farmers measure the PBFT accurately and conveniently,and improve the pig production efficiency.展开更多
Backfat thickness is a good predictor of carcass lean content,an economically important trait,and a main breeding target in pig improvement.In this study,the candidate genes and genomic regions associated with the ten...Backfat thickness is a good predictor of carcass lean content,an economically important trait,and a main breeding target in pig improvement.In this study,the candidate genes and genomic regions associated with the tenth rib backfat thickness trait were identified in two independent pig populations,using a genome-wide association study of porcine 60K SNP genotype data applying the compressed mixed linear model(CMLM)statistical method.For each population,30 most significant single-nucleotide polymorphisms(SNPs)were selected and SNP annotation implemented using Sus scrofa Build 10.2.In the first population,25 significant SNPs were distributed on seven chromosomes,and SNPs on SSC1 and SSC7 showed great significance for fat deposition.The most significant SNP(ALGA0006623)was located on SSC1,upstream of the MC4R gene.In the second population,27 significant SNPs were recognized by annotation,and 12 SNPs on SSC12 were related to fat deposition.Two haplotype blocks,M1GA0016251-MARC0075799 and ALGA0065251-MARC0014203-M1GA0016298-ALGA0065308,were detected in significant regions where the PIPNC1 and GH1 genes were identified as contributing to fat metabolism.The results indicated that genetic mechanism regulating backfat thickness is complex,and that genome-wide associations can be affected by populations with different genetic backgrounds.展开更多
Background Excessive backfat deposition lowering carcass grade is a major concern in the pig industry,especially in most breeds of obese type pigs.The mechanisms involved in adipogenesis and fat accumulation in pigs r...Background Excessive backfat deposition lowering carcass grade is a major concern in the pig industry,especially in most breeds of obese type pigs.The mechanisms involved in adipogenesis and fat accumulation in pigs remain unclear.Lysine 2-hydroxyisobutyrylation(Khib),is a novel protein post-translational modification(PTM),which play an important role in transcription,energy metabolism and metastasis of cancer cells,but its role in adipogenesis and fat accumulation has not been shown.Results In this study,we first analyzed the modification levels of acetylation(Kac),Khib,crotonylation(Kcr)and succinylation(Ksu)of fibro-adipogenic progenitors(FAPs),myogenic precursors(Myo)and mesenchymal stem cells(MSCs)with varied differentiation potential,and found that only Khib modification in FAPs was significantly higher than that in MSCs.Consistently,in parallel with its regulatory enzymes lysine acetyltransferase 5(KAT5)and histone deacetylase 2(HDAC2)protein levels,the Khib levels increased quadratically(P<0.01)during adipogenic differentiation of FAPs.KAT5 knockdown in FAPs inhibited adipogenic differentiation,while HDAC2 knockdown enhanced adipogenic differentiation.We also demonstrated that Khib modification favored to adipogenic differentiation and fat accumulation by comparing Khib levels in FAPs and backfat tissues both derived from obese-type pigs(Laiwu pigs)and lean-type pigs(Duroc pigs),respectively.Accordingly,the expression patterns of KAT5 and HDAC2 matched well to the degree of backfat accumulation in obese-and lean-type pigs.Conclusions From the perspective of protein translational modification,we are the first to reveal the role of Khib in adipogenesis and fat deposition in pigs,and provided new clues for the improvement of fat accumulation and distribution as expected via genetic selection and nutritional strategy in obese-type pigs.展开更多
【目的】筛选和识别大河猪背脂沉积相关的关键候选基因。【方法】对高背膘和低背膘各6头大河猪的背部脂肪组织进行转录组测序,筛选差异表达基因并对其GO功能和KEGG通路富集进行分析,结合蛋白质—蛋白质互作网络构建,对大河猪背脂沉积关...【目的】筛选和识别大河猪背脂沉积相关的关键候选基因。【方法】对高背膘和低背膘各6头大河猪的背部脂肪组织进行转录组测序,筛选差异表达基因并对其GO功能和KEGG通路富集进行分析,结合蛋白质—蛋白质互作网络构建,对大河猪背脂沉积关键基因进行发掘与鉴定,再随机挑选3个关键基因进行RT-qPCR验证。【结果】共检测到214个差异表达基因,在高背膘组大河猪中有107个基因上调,107个基因下调。这些基因极显著富集于氧酸代谢、有机酸代谢、脂质代谢、羧酸代谢等生物学过程,以及过氧化物酶体增殖物激活受体(peroxisome proliferator-activated receptor,PPAR)信号通路、腺苷酸活化蛋白激酶(AMP-activated protein kinase,AMPK)信号通路、丙酮酸代谢、三羧酸循环等脂肪沉积调控通路(P<0.01),其中,PCK1、ME1、ACLY、ACACA、FASN和SCD为背脂沉积的关键基因。随机挑选的3个关键基因(PCK1、ACLY和ME1)在高、低背膘组大河猪背部脂肪中的表达差异达到显著或极显著水平(P<0.05或P<0.01)。【结论】研究结果初步鉴定了大河猪背脂沉积的关键基因,为深入揭示猪背脂沉积的分子机制及促进瘦肉率等背脂相关性状的遗传改良提供了科学基础和依据。展开更多
基金financially supported by the innovation research team for modern agricultural industry and technology in Beijing
文摘Background： Fatness traits in animals are important for their growth, meat quality, reproductive performance, and immunity. The liver is the principal organ of the regulation of lipid metabolism, and this study used massive parallelized high-throughput sequencing technologies to determine the porcine liver tissue transcriptome architecture of two full-sibling Songliao black pigs harboring extremely different phenotypes of backfat thickness. Results： The total number of reads produced for each sample was in the region of 53 million, and 8,226 novel transcripts were detected. Approximately 92 genes were differentially regulated in the liver tissue, while 31 spliced transcripts and 33 primary transcripts showed significantly differential expression between pigs with higher and lower backfat thickness. Genes that were differentially expressed were involved in the metabolism of various substances, smal molecule biochemistry, and molecular transport. Conclusions： Genes involved in the regulation of iipids could play an important role in lipid and fatty acid metabolism in the liver. These results could help us understand how liver metabolism affects the backfat thickness of pigs.
基金supported by the China Postdoctoral Science Foundation[Grant Number BX20240146 and 2024M761230]Key Project of Research and Development Plan in Jiangxi Province[Grant Number 20243BCC31001].
文摘Background Backfat thickness(BFT)is a vital economic trait in pigs,reflecting subcutaneous fat levels that affect meat quality and production efficiency.As a complex trait shaped by multiple genetic factors,BFT has been studied using genome-wide association studies(GWAS)and linkage analyses to locate fat-related quantitative trait loci(QTLs),but pinpointing causal variants and genes is hindered by linkage disequilibrium and limited regulatory data.This study aimed to dissect the QTLs affecting BFT on Sus scrofa chromosome 1(SSC1),elucidating regulatory variants,effector genes,and the cell types involved.Results Using whole-genome genotyping data from 3,578 pigs and phenotypic data for five BFT traits,we identified a 630.6 kb QTL on SSC1 significantly associated with these traits via GWAS and fine-mapping,pinpointing 34 candidate causal variants.Using deep convolutional neural networks to predict regulatory activity from sequence data integrated with detailed pig epigenetic profiles,we identified five SNPs potentially affecting enhancer activity in specific tissues.Notably,rs342950505(SSC1:161,123,588)influences weak enhancer activity across multiple tissues,including the brain.High-throughput chromosome conformation capture(Hi-C)analysis identified that rs342950505 interacts with eight genes.Chromatin state annotations confirmed enhancer activity at this QTL in the cerebellum.Leveraging these insights,single-cell ATAC-seq revealed a chromatin accessibility peak encompassing rs342950505 that regulates PMAIP1 expression in inhibitory neurons via enhancer-mediated mechanisms,with an adjacent peak modulating CCBE1 expression in neuroblasts and granule cells.Transcriptome-wide association studies(TWAS)confirmed PMAIP1's role in the hypothalamus,and Mendelian randomization(MR)validated PMAIP1 and CCBE1 as key brain expression quantitative trait locus(eQTL)effectors.We propose that the variant rs342950505,located within a regulatory peak,modulates PMAIP1 expression in inhibitory neurons,potentially influencing energy homeostasis via hypothalamic regulation.Similarly,CCBE1 may contribute to this process.Conclusions Our results,through systematic dissection of pleiotropic BFT-associated loci,provide a framework to elucidate regulatory mechanisms of complex traits,offering insights into polygenic control through lipid metabolism and neural signaling pathways.
基金supported by the China Agriculture Research System(CARS-35-PIG)the National Natural Science Foundation of China(32272847,U22A20516)+1 种基金the National Key Research and Development Program of China(No.2021YFF1000602)the Key Research and Development Program of Shaanxi Province(No.2022ZDLNY01–04)。
文摘Background Increased backfat thickness of sows in early gestation is negative to reproductive performance.Endometrial receptivity is an important determinant of reproductive success,but it is unclear whether the effect of sow backfat thickness on litter size is associated with endometrial receptivity and whether melatonin treatment may have benefits.The present study seeks to answer these questions through in vitro and in vivo investigations.Results Excessive lipid deposition and lower melatonin levels in the uterus are detrimental to endometrial receptivity and embryo implantation in high backfat thickness sows.In cells treated with melatonin,the MT2/PI3K/LIF axis played a role in reducing lipid accumulation in porcine endometrial epithelium cells and improved endometrial receptivity.Furthermore,we found a reduction of lipids in the uterus after eight weeks of intraperitoneal administration of melatonin to HFD mice.Notably,melatonin treatment caused a significant reduction in the deposition of endometrial collagen,an increase in the number of glands,and repair of the pinopode structure,ultimately improving endometrial receptivity,promoting embryo implantation,and increasing the number of litter size of mice.Conclusions Collectively,the finding reveals the harmful effects of high backfat thickness sows on embryo implantation and highlight the role of melatonin and the MT2/PI3K/LIF axis in improving endometrial receptivity by enhancing metabolism and reducing the levels of uterine lipids in obese animals.
基金supported by Project of Science Operating Expenses from Ministry of Education of China(Grant No.2017PT19)Chinese Universities Scientific Fund(Grant No.2017XD003).
文摘The measurement of pig backfat thickness(PBFT)has to stand up to challenges with the reliability,accuracy,and convenience.Acquiring PBFT timely and precisely from a finite distance is extremely necessary to improve the process of pig production and implement effective management.In an attempt to alleviate these problems,an online handheld terminal was designed with a new method based on ultrasonic technology for measuring PBFT during the process of pig breeding,which can overcome the difficulties encountered in other destructive means.The terminal comprised three main components:a main microcontroller unit(MCU)to measure PBFT,a RFID module to identify each pig and send data(e.g.identity,measurement time and PBFT)to a server via wireless transmission module,and an ultrasonic transducer to drive and receive signals between them.A measurement error within 0-1 mm was acquired through testing three groups of samples.Results indicated that this handheld terminal had a required accuracy and proved that the ultrasonic wave processing method can be deployed in a mobile terminal for PBFT measurement.It also provided a feasible nondestructive alternative to measure PBFT.Associated with information management software platform,this method may ultimately help pig production farmers measure the PBFT accurately and conveniently,and improve the pig production efficiency.
基金This study was supported by the National Science Foundation of China(31172192)New Century Excellent Talents(NCET-11-0646)Fundamental Research Funds for the Central Universities(2011JQ009,2012PY009).
文摘Backfat thickness is a good predictor of carcass lean content,an economically important trait,and a main breeding target in pig improvement.In this study,the candidate genes and genomic regions associated with the tenth rib backfat thickness trait were identified in two independent pig populations,using a genome-wide association study of porcine 60K SNP genotype data applying the compressed mixed linear model(CMLM)statistical method.For each population,30 most significant single-nucleotide polymorphisms(SNPs)were selected and SNP annotation implemented using Sus scrofa Build 10.2.In the first population,25 significant SNPs were distributed on seven chromosomes,and SNPs on SSC1 and SSC7 showed great significance for fat deposition.The most significant SNP(ALGA0006623)was located on SSC1,upstream of the MC4R gene.In the second population,27 significant SNPs were recognized by annotation,and 12 SNPs on SSC12 were related to fat deposition.Two haplotype blocks,M1GA0016251-MARC0075799 and ALGA0065251-MARC0014203-M1GA0016298-ALGA0065308,were detected in significant regions where the PIPNC1 and GH1 genes were identified as contributing to fat metabolism.The results indicated that genetic mechanism regulating backfat thickness is complex,and that genome-wide associations can be affected by populations with different genetic backgrounds.
基金financially supported by the National Key Research and Development Program of China(Grant No.2023YFD1301300)。
文摘Background Excessive backfat deposition lowering carcass grade is a major concern in the pig industry,especially in most breeds of obese type pigs.The mechanisms involved in adipogenesis and fat accumulation in pigs remain unclear.Lysine 2-hydroxyisobutyrylation(Khib),is a novel protein post-translational modification(PTM),which play an important role in transcription,energy metabolism and metastasis of cancer cells,but its role in adipogenesis and fat accumulation has not been shown.Results In this study,we first analyzed the modification levels of acetylation(Kac),Khib,crotonylation(Kcr)and succinylation(Ksu)of fibro-adipogenic progenitors(FAPs),myogenic precursors(Myo)and mesenchymal stem cells(MSCs)with varied differentiation potential,and found that only Khib modification in FAPs was significantly higher than that in MSCs.Consistently,in parallel with its regulatory enzymes lysine acetyltransferase 5(KAT5)and histone deacetylase 2(HDAC2)protein levels,the Khib levels increased quadratically(P<0.01)during adipogenic differentiation of FAPs.KAT5 knockdown in FAPs inhibited adipogenic differentiation,while HDAC2 knockdown enhanced adipogenic differentiation.We also demonstrated that Khib modification favored to adipogenic differentiation and fat accumulation by comparing Khib levels in FAPs and backfat tissues both derived from obese-type pigs(Laiwu pigs)and lean-type pigs(Duroc pigs),respectively.Accordingly,the expression patterns of KAT5 and HDAC2 matched well to the degree of backfat accumulation in obese-and lean-type pigs.Conclusions From the perspective of protein translational modification,we are the first to reveal the role of Khib in adipogenesis and fat deposition in pigs,and provided new clues for the improvement of fat accumulation and distribution as expected via genetic selection and nutritional strategy in obese-type pigs.
文摘【目的】筛选和识别大河猪背脂沉积相关的关键候选基因。【方法】对高背膘和低背膘各6头大河猪的背部脂肪组织进行转录组测序,筛选差异表达基因并对其GO功能和KEGG通路富集进行分析,结合蛋白质—蛋白质互作网络构建,对大河猪背脂沉积关键基因进行发掘与鉴定,再随机挑选3个关键基因进行RT-qPCR验证。【结果】共检测到214个差异表达基因,在高背膘组大河猪中有107个基因上调,107个基因下调。这些基因极显著富集于氧酸代谢、有机酸代谢、脂质代谢、羧酸代谢等生物学过程,以及过氧化物酶体增殖物激活受体(peroxisome proliferator-activated receptor,PPAR)信号通路、腺苷酸活化蛋白激酶(AMP-activated protein kinase,AMPK)信号通路、丙酮酸代谢、三羧酸循环等脂肪沉积调控通路(P<0.01),其中,PCK1、ME1、ACLY、ACACA、FASN和SCD为背脂沉积的关键基因。随机挑选的3个关键基因(PCK1、ACLY和ME1)在高、低背膘组大河猪背部脂肪中的表达差异达到显著或极显著水平(P<0.05或P<0.01)。【结论】研究结果初步鉴定了大河猪背脂沉积的关键基因,为深入揭示猪背脂沉积的分子机制及促进瘦肉率等背脂相关性状的遗传改良提供了科学基础和依据。
