Leptin receptor(LEPR)plays a vital role in obesity in humans and animals.The objective of this study is to assess LEPR functional variants for chicken adipose deposition by integration of association and in-silico ana...Leptin receptor(LEPR)plays a vital role in obesity in humans and animals.The objective of this study is to assess LEPR functional variants for chicken adipose deposition by integration of association and in-silico analysis using a unique chicken population,the Northeast Agricultural University broiler lines divergently selected for abdominal fat content(NEAUHLF).Five online bioinformatics tools were used to predict the functionality of the single nucleotide polymorphisms(SNPs)in coding region.Further,the possible structure–function relationship of high confidence SNPs was determined by bioinformatics analyses,including the conservation and stability analysis based on amino acid residues,prediction of protein ligand-binding sites,and the superposition of protein tertiary structure.Meanwhile,we analyzed the association between abdominal fat traits and 20 polymorphisms of chicken LEPR gene.The integrated results showed that rs731962924(N867I)and rs13684622(C1002R)could lead to striking changes in the structure and function of proteins,of which rs13684622(C1002R)was significantly associated with abdominal fat weight(AFW,P=0.0413)and abdominal fat percentage(AFP,P=0.0260)in chickens.Therefore,we are of the opinion that rs13684622(C1002R)may be an essential functional SNP affecting chicken abdominal fat deposition,and potentially applied to improvement of broiler abdominal fat in molecular marker-assisted selection(MAS)program.Additionally,the coupling of association with computer electronic predictive analysis provides a new avenue to identify important molecular markers for breeders.展开更多
Obesity presents a serious threat to human health and broiler performance.The expansion of adipose tissue is mainly regulated by the differentiation of preadipocytes.The differentiation of preadipocytes is a complex b...Obesity presents a serious threat to human health and broiler performance.The expansion of adipose tissue is mainly regulated by the differentiation of preadipocytes.The differentiation of preadipocytes is a complex biological process regulated by a variety of transcription factors and signaling pathways.Previous studies have shown that the transcription factor HMG-box protein 1(HBP1)can regulate the differentiation of mouse 3T3-L1 preadipocytes by activating the Wnt/β-catenin signaling pathway.However,it is unclear whether HBP1 involved in chicken preadipocyte differentiation and which signaling pathways it regulates.The aim of the current study was to explore the biological function and molecular regulatory mechanism of HBP1 in the differentiation of chicken preadipocytes.The expression patterns of chicken HBP1 in abdominal adipose tissue and during preadipocyte differentiation were analyzed by RT-qPCR and Western blot.The preadipocyte stably overexpressing HBP1 or knockout HBP1 and their control cell line were used to analyze the effect of HBP1 on preadipocyte differentiation by oil red O staining,RT-qPCR and Western blot.Cignal 45-Pathway Reporter Array was used to screen the signal pathways that HBP1 regulates in the differentiation of chicken preadipocytes.Chemical inhibitor and siRNA for signal transducer and activator of transcription 3(STAT3)were used to analyze the effect of STAT3 on preadipocyte differentiation.The preadipocyte stably overexpressing HBP1 was transfected by the siRNA of STAT3 or treated with a chemical inhibitor of STAT3 for the rescue experiment.The results of gene expression analysis showed that the expression of HBP1 was related to abdominal fat deposition and preadipocyte differentiation in chickens.The results of function gain and loss experiments indicated that overexpression/knockout of HBP1 in chicken preadipocytes could inhibit/promote(P<0.05)lipid droplet deposition and the expression of adipogenesis-related genes.Mechanismlly,HBP1 activates(P<0.05)the signal transducer and activator of transcription 3(STAT3)signaling pathway by targeting janus kinase 2(JAK2)transcription.The results of functional rescue experiments indicated that STAT3 signaling mediated the regulation of HBP1 on chicken preadipocyte differentiation.In conclusion,HBP1 inhibits chicken preadipocyte differentiation by activating the STAT3 signaling pathway via directly enhancing JAK2 expression.Our findings provided new insights for further analysis of the molecular genetic basis of chicken adipose tissue growth and development.展开更多
Improving the production of broiler chicken meat has been a goal of broiler breeding programs worldwide for many years. However, the genetic architectures of skeletal muscle production traits in chickens have not yet ...Improving the production of broiler chicken meat has been a goal of broiler breeding programs worldwide for many years. However, the genetic architectures of skeletal muscle production traits in chickens have not yet been fully elucidated. In the present study, a total of 519 F_(2) birds, derived from a cross of Arbor Acres broiler and Baier layer, were re-sequenced(26 F_(0) individuals were re-sequenced at a 10-fold depth;519 F_(2) individuals were re-sequenced at a 3-fold depth) and the coupling of genome-wide association study(GWAS) and selection signatures(FST(fixation index) and θπ(nucleotide diversity)) was carried out to pinpoint the associated loci and genes that contribute to pectoral muscle weight(PMW) and thigh muscle weight(TMW). A total of 7 890 258 single nucleotide polymorphisms(SNPs) remained to be analyzed after quality control and imputation. The integration of GWAS and selection signature analyses revealed that genetic determinants responsible for skeletal muscle production traits were mainly localized on chromosomes 1(168.95–172.43 Mb) and 4(74.37–75.23 Mb). A total of 17 positional candidate genes(PCGs)(LRCH1, CDADC1, CAB39 L, LOC112531568, LOC112531569, FAM124 A, FOXO1, NBEA, GPALPP1, RUBCNL, ARL11, KPNA3, LHFP, GBA3, LOC112532426, KCNIP4, and SLIT2) were identified in these regions. In particular, KPNA3 and FOXO1 were the most promising candidates for meat production in chickens. These findings will help enhance our understanding of the genetic architecture of chicken muscle production traits, and the significant SNPs identified could be promising candidates for integration into practical breeding programs such as genome-wide selection(GS) to improve the meat yield of chickens.展开更多
基金This work was supported by the National Natural Science Foundation of China(31572394)the China Agriculture Research System of MOF and MARA(CARS-41)the White Feather Broiler Breeding Joint Project of the Ministry of Agriculture and Rural Affairs of China(19190526).
文摘Leptin receptor(LEPR)plays a vital role in obesity in humans and animals.The objective of this study is to assess LEPR functional variants for chicken adipose deposition by integration of association and in-silico analysis using a unique chicken population,the Northeast Agricultural University broiler lines divergently selected for abdominal fat content(NEAUHLF).Five online bioinformatics tools were used to predict the functionality of the single nucleotide polymorphisms(SNPs)in coding region.Further,the possible structure–function relationship of high confidence SNPs was determined by bioinformatics analyses,including the conservation and stability analysis based on amino acid residues,prediction of protein ligand-binding sites,and the superposition of protein tertiary structure.Meanwhile,we analyzed the association between abdominal fat traits and 20 polymorphisms of chicken LEPR gene.The integrated results showed that rs731962924(N867I)and rs13684622(C1002R)could lead to striking changes in the structure and function of proteins,of which rs13684622(C1002R)was significantly associated with abdominal fat weight(AFW,P=0.0413)and abdominal fat percentage(AFP,P=0.0260)in chickens.Therefore,we are of the opinion that rs13684622(C1002R)may be an essential functional SNP affecting chicken abdominal fat deposition,and potentially applied to improvement of broiler abdominal fat in molecular marker-assisted selection(MAS)program.Additionally,the coupling of association with computer electronic predictive analysis provides a new avenue to identify important molecular markers for breeders.
基金supported by the China Agriculture Research System of MOF and MARA of China (CARS41)
文摘Obesity presents a serious threat to human health and broiler performance.The expansion of adipose tissue is mainly regulated by the differentiation of preadipocytes.The differentiation of preadipocytes is a complex biological process regulated by a variety of transcription factors and signaling pathways.Previous studies have shown that the transcription factor HMG-box protein 1(HBP1)can regulate the differentiation of mouse 3T3-L1 preadipocytes by activating the Wnt/β-catenin signaling pathway.However,it is unclear whether HBP1 involved in chicken preadipocyte differentiation and which signaling pathways it regulates.The aim of the current study was to explore the biological function and molecular regulatory mechanism of HBP1 in the differentiation of chicken preadipocytes.The expression patterns of chicken HBP1 in abdominal adipose tissue and during preadipocyte differentiation were analyzed by RT-qPCR and Western blot.The preadipocyte stably overexpressing HBP1 or knockout HBP1 and their control cell line were used to analyze the effect of HBP1 on preadipocyte differentiation by oil red O staining,RT-qPCR and Western blot.Cignal 45-Pathway Reporter Array was used to screen the signal pathways that HBP1 regulates in the differentiation of chicken preadipocytes.Chemical inhibitor and siRNA for signal transducer and activator of transcription 3(STAT3)were used to analyze the effect of STAT3 on preadipocyte differentiation.The preadipocyte stably overexpressing HBP1 was transfected by the siRNA of STAT3 or treated with a chemical inhibitor of STAT3 for the rescue experiment.The results of gene expression analysis showed that the expression of HBP1 was related to abdominal fat deposition and preadipocyte differentiation in chickens.The results of function gain and loss experiments indicated that overexpression/knockout of HBP1 in chicken preadipocytes could inhibit/promote(P<0.05)lipid droplet deposition and the expression of adipogenesis-related genes.Mechanismlly,HBP1 activates(P<0.05)the signal transducer and activator of transcription 3(STAT3)signaling pathway by targeting janus kinase 2(JAK2)transcription.The results of functional rescue experiments indicated that STAT3 signaling mediated the regulation of HBP1 on chicken preadipocyte differentiation.In conclusion,HBP1 inhibits chicken preadipocyte differentiation by activating the STAT3 signaling pathway via directly enhancing JAK2 expression.Our findings provided new insights for further analysis of the molecular genetic basis of chicken adipose tissue growth and development.
基金supported by the National Natural Science Foundation of China(31572394)the China Agriculture Research System of MOF and MARA(CARS-41)the White Feather Broiler Breeding Joint Project of the Ministry of Agriculture and Rural Affairs of China(19190526)。
文摘Improving the production of broiler chicken meat has been a goal of broiler breeding programs worldwide for many years. However, the genetic architectures of skeletal muscle production traits in chickens have not yet been fully elucidated. In the present study, a total of 519 F_(2) birds, derived from a cross of Arbor Acres broiler and Baier layer, were re-sequenced(26 F_(0) individuals were re-sequenced at a 10-fold depth;519 F_(2) individuals were re-sequenced at a 3-fold depth) and the coupling of genome-wide association study(GWAS) and selection signatures(FST(fixation index) and θπ(nucleotide diversity)) was carried out to pinpoint the associated loci and genes that contribute to pectoral muscle weight(PMW) and thigh muscle weight(TMW). A total of 7 890 258 single nucleotide polymorphisms(SNPs) remained to be analyzed after quality control and imputation. The integration of GWAS and selection signature analyses revealed that genetic determinants responsible for skeletal muscle production traits were mainly localized on chromosomes 1(168.95–172.43 Mb) and 4(74.37–75.23 Mb). A total of 17 positional candidate genes(PCGs)(LRCH1, CDADC1, CAB39 L, LOC112531568, LOC112531569, FAM124 A, FOXO1, NBEA, GPALPP1, RUBCNL, ARL11, KPNA3, LHFP, GBA3, LOC112532426, KCNIP4, and SLIT2) were identified in these regions. In particular, KPNA3 and FOXO1 were the most promising candidates for meat production in chickens. These findings will help enhance our understanding of the genetic architecture of chicken muscle production traits, and the significant SNPs identified could be promising candidates for integration into practical breeding programs such as genome-wide selection(GS) to improve the meat yield of chickens.
