Mutations of the melanocortin-4 receptor (MC4R) gene are associated with the appetite, obesity; growth in pig, mice; human. But little is known about the function of chicken MC4R gene. In this study, F2 chicken resour...Mutations of the melanocortin-4 receptor (MC4R) gene are associated with the appetite, obesity; growth in pig, mice; human. But little is known about the function of chicken MC4R gene. In this study, F2 chicken resource population derived from broilers crossing to Silky was screened for the polymorphisms of the MC4R gene using PCR-single strand conformation polymorphism (PCR-SSCP); DNA sequencing methods. Four single nucleotide polymorphisms (SNPs) sites were found. The mutation (C→T) in the 5′ regulation region of chicken MC4R gene results in one more NF-E2; cap transcription factor binding sites in the mutation allele than in the wild allele. One missense mutation (G→A) occurs in the coding region (61nt), which changes the glycine to arginine. Moreover, in the coding region there are 2 synonymous mutations, one G→T mutation at 315nt; one C→T mutation at 336nt. Least square analysis of the SNPs; carcass traits showed that BB, DD; FF genotypes are significantly associated with body weight, carcass weight (or half carcass weight),; leg muscle weight (P>0.05 or P>0.01). But no significant association between the genotypes; abdominal fat weight is found. The results present the evidence that the chicken MC4R gene can be selected as the major candidate gene for the carcass traits such as body weight; growth.展开更多
目的:探讨黑素皮质素4受体(melanocortin four receptor,MC4R)rs489693多态性对奥氮平治疗12周后精神分裂症患者糖脂代谢的影响。方法:选取171例精神分裂症患者,根据DNA测序法检测MC4R基因489693位点的多态性分为AA组12例,AC组59例,CC组...目的:探讨黑素皮质素4受体(melanocortin four receptor,MC4R)rs489693多态性对奥氮平治疗12周后精神分裂症患者糖脂代谢的影响。方法:选取171例精神分裂症患者,根据DNA测序法检测MC4R基因489693位点的多态性分为AA组12例,AC组59例,CC组100例,于治疗前和治疗12周后测定血糖、血脂水平,比较3组间各变量的差异,并统计分析治疗后患者糖脂异常发生率。结果:分析发现治疗12周后AA组血糖净增大于CC组(P<0.05),AA组胆固醇、甘油三酯净增均大于AC组和CC组(P<0.05);治疗后AA组患者血糖、至少一项血脂异常发生率大于AC组和CC组(P<0.01)。结论:MC4R基因rs489693的基因多态性与奥氮平治疗精神分裂症患者发生糖脂代谢紊乱具有一定关系。展开更多
The rostral ventromedial medulla （RVM） is a prominent component of the descending modulatory system involved in the control of spinal nociceptive transmission. In the current study, we investigated melanocortin-4 re...The rostral ventromedial medulla （RVM） is a prominent component of the descending modulatory system involved in the control of spinal nociceptive transmission. In the current study, we investigated melanocortin-4 receptor （MC4R） expression in the RVM, where the neurons involved in modulation of nociception reside. Using a line of mice expressing green fluorescent protein （GFP） under the control of the MC4R promoter, we found a large number of GFP-positive neurons in the RVM [nucleus raphe magnus （NRM） and nucleus gigantocellularis pars a （NGCa）]. Fluorescence immunohisto- chemistry revealed that approximately 10% of MC4R-GFP-positive neurons coexpressed tyrosine hydroxylase, indicating that they were catecholaminergic, whereas 50%-75% of those coexpressed tryp- tophan hydroxylase, indicating that they were serotonergic. Our findings support the hypothesis that MC4R signaling in RVM may modulate the activity of serotonergic sympathetic outflow sensitive to nociceptive signals, and that MC4R signaling in RVM may contribute to the descending modulation of nociceptive transmission.展开更多
Melanocortin 4 receptor(MC4R),the most important monogenetic cause of human metabolic disorders,has been of great interest to many researchers in the field of energy homeostasis and public health.Because MC4R is a vit...Melanocortin 4 receptor(MC4R),the most important monogenetic cause of human metabolic disorders,has been of great interest to many researchers in the field of energy homeostasis and public health.Because MC4R is a vital pharmaceutical target for maintaining controllable appetite and body weight for professional athletes,previous studies have mainly focused on the central,rather than the peripheral,roles of MC4R.Thus,the local expression of MC4R and its behavioral regulation remain unclear.In an attempt to shed light on different directions for future studies of MC4R signaling,we review a series of recent and important studies exploring the peripheral functions of MC4R and the direct physiological interaction between peripheral organs and central MC4R neurons in this article.展开更多
目的应用Meta分析系统评价黑色素皮质激素第四受体基因（melanocortin-4receptor gene,MC4R）rs17782313与儿童肥胖易感性的关系,以得到更有说服力的结论。方法利用计算机检索数据库PubMed,中国知网、万方等,手工检索纳入文献的参考文...目的应用Meta分析系统评价黑色素皮质激素第四受体基因（melanocortin-4receptor gene,MC4R）rs17782313与儿童肥胖易感性的关系,以得到更有说服力的结论。方法利用计算机检索数据库PubMed,中国知网、万方等,手工检索纳入文献的参考文献。采用STATA 11.0软件进行Meta分析。利用随机效应模型或固定效应模型计算其合并比值比（OR）和95%可信区间（95%CI）,以及合并加权均数差（WMD）的值。结果共有12个研究纳入研究,其中在纯合子模型（OR=1.84,95%CI：1.44～2.36,Phet=0.001）、杂合子模型（OR=1.48,95%CI：1.29～1.70,Phet=0.756）、显性模型（OR=1.67,95%CI：1.39～1.99,Phet=0.082）和隐性模型（OR=1.35,95%CI：1.19～1.55,Phet=0.000）,差异均有统计学意义。在基因型与体质指数（body mass index,BMI）Z-score定量关联性分析中,发现rs17782313T〉C的突变会影响儿童的BMI Z-score（WMD=0.14,95%CI：0.06～0.23,CC vs TT）。结论Meta分析研究结果证实了MC4R rs17782313与儿童肥胖的关系。展开更多
Objective To investigate how F261S mutation identified from Chinese obese patients affects the function of melanocorfin 4 receptor (MC4R) and to analyze the obesity-related phenotypes in subjects carrying the F261S mu...Objective To investigate how F261S mutation identified from Chinese obese patients affects the function of melanocorfin 4 receptor (MC4R) and to analyze the obesity-related phenotypes in subjects carrying the F261S mutation. Methods F261S mutant of MC4R was generated by site-directed mutagenesis. Plasmids encoding wild-type or F261S mutant of MC4R were transfected into HEK293 and COS-7 cells to examine their functional characteristics. Signaling properties of F261S MC4R were assessed by measuring intracellular cAMP levels in response to α-MSH stimulation. Cell surface expression of F261S MC4R was compared with that of wild-type MC4R. Clinical examinations were performed in subjects carrying F261S mutation and in non-mutated controls. Results The a-MSH-stimulated reporter gene activity was significantly reduced in cells expressing F261S MC4R, with a maximal response equal to 57% of wild-type MC4R. The F261S mutation also led to a significant change in the EC50 value compared with the wild-type receptor (P〈0.01). Immunofluorescent assay revealed a marked reduction in plasma membrane localization of the MC4R in cells expressing the F261S mutant receptor. The resting metabolic rate and fat composition of the mutant carriers were not significantly different from those of the non-mutated obese controls. Conclusions The decreased response to α-MSH due to the intracellular retention of MC4R may cause early-onset obesity in the F261S pedigree of Chinese.展开更多
基金supported by the Funds for Creative Research Groups of National Natural Science Foundation of China,the Special Funds for Major State Basic Research of China(Grant No.G20000161).
文摘Mutations of the melanocortin-4 receptor (MC4R) gene are associated with the appetite, obesity; growth in pig, mice; human. But little is known about the function of chicken MC4R gene. In this study, F2 chicken resource population derived from broilers crossing to Silky was screened for the polymorphisms of the MC4R gene using PCR-single strand conformation polymorphism (PCR-SSCP); DNA sequencing methods. Four single nucleotide polymorphisms (SNPs) sites were found. The mutation (C→T) in the 5′ regulation region of chicken MC4R gene results in one more NF-E2; cap transcription factor binding sites in the mutation allele than in the wild allele. One missense mutation (G→A) occurs in the coding region (61nt), which changes the glycine to arginine. Moreover, in the coding region there are 2 synonymous mutations, one G→T mutation at 315nt; one C→T mutation at 336nt. Least square analysis of the SNPs; carcass traits showed that BB, DD; FF genotypes are significantly associated with body weight, carcass weight (or half carcass weight),; leg muscle weight (P>0.05 or P>0.01). But no significant association between the genotypes; abdominal fat weight is found. The results present the evidence that the chicken MC4R gene can be selected as the major candidate gene for the carcass traits such as body weight; growth.
文摘目的:探讨黑素皮质素4受体(melanocortin four receptor,MC4R)rs489693多态性对奥氮平治疗12周后精神分裂症患者糖脂代谢的影响。方法:选取171例精神分裂症患者,根据DNA测序法检测MC4R基因489693位点的多态性分为AA组12例,AC组59例,CC组100例,于治疗前和治疗12周后测定血糖、血脂水平,比较3组间各变量的差异,并统计分析治疗后患者糖脂异常发生率。结果:分析发现治疗12周后AA组血糖净增大于CC组(P<0.05),AA组胆固醇、甘油三酯净增均大于AC组和CC组(P<0.05);治疗后AA组患者血糖、至少一项血脂异常发生率大于AC组和CC组(P<0.01)。结论:MC4R基因rs489693的基因多态性与奥氮平治疗精神分裂症患者发生糖脂代谢紊乱具有一定关系。
基金supported by grants from National Natural Science Foundation of China(No.81071307,No.81271766,and No.81673964)Special Fund of Fundamental Scientific Research Business Expense for Higher School of Central Government(No.2012TS060)
文摘The rostral ventromedial medulla （RVM） is a prominent component of the descending modulatory system involved in the control of spinal nociceptive transmission. In the current study, we investigated melanocortin-4 receptor （MC4R） expression in the RVM, where the neurons involved in modulation of nociception reside. Using a line of mice expressing green fluorescent protein （GFP） under the control of the MC4R promoter, we found a large number of GFP-positive neurons in the RVM [nucleus raphe magnus （NRM） and nucleus gigantocellularis pars a （NGCa）]. Fluorescence immunohisto- chemistry revealed that approximately 10% of MC4R-GFP-positive neurons coexpressed tyrosine hydroxylase, indicating that they were catecholaminergic, whereas 50%-75% of those coexpressed tryp- tophan hydroxylase, indicating that they were serotonergic. Our findings support the hypothesis that MC4R signaling in RVM may modulate the activity of serotonergic sympathetic outflow sensitive to nociceptive signals, and that MC4R signaling in RVM may contribute to the descending modulation of nociceptive transmission.
基金Fundings supported by grants from the National Key Research and Development Program of China(Grant No.2017YFA0103902,2018YFA0800300,2019YFA0801900,2019YFA0111400)National Natural Science Foundation of China(Grant No.31771283,91749104,31971074)+3 种基金the Fundamental Research Funds for the Central Universities of Tongji University(No.22120190210)Innovative Research Team of High-Level Local Universities in Shanghai(No.SSMUZDCX20180700)Key Laboratory Program of the Education Commission of Shanghai Municipality(No.DSYS14005)the Science and Technology Innovation Action Plan of Shanghai Science and Technology Committee(No.18140901300).
文摘Melanocortin 4 receptor(MC4R),the most important monogenetic cause of human metabolic disorders,has been of great interest to many researchers in the field of energy homeostasis and public health.Because MC4R is a vital pharmaceutical target for maintaining controllable appetite and body weight for professional athletes,previous studies have mainly focused on the central,rather than the peripheral,roles of MC4R.Thus,the local expression of MC4R and its behavioral regulation remain unclear.In an attempt to shed light on different directions for future studies of MC4R signaling,we review a series of recent and important studies exploring the peripheral functions of MC4R and the direct physiological interaction between peripheral organs and central MC4R neurons in this article.
文摘目的应用Meta分析系统评价黑色素皮质激素第四受体基因（melanocortin-4receptor gene,MC4R）rs17782313与儿童肥胖易感性的关系,以得到更有说服力的结论。方法利用计算机检索数据库PubMed,中国知网、万方等,手工检索纳入文献的参考文献。采用STATA 11.0软件进行Meta分析。利用随机效应模型或固定效应模型计算其合并比值比（OR）和95%可信区间（95%CI）,以及合并加权均数差（WMD）的值。结果共有12个研究纳入研究,其中在纯合子模型（OR=1.84,95%CI：1.44～2.36,Phet=0.001）、杂合子模型（OR=1.48,95%CI：1.29～1.70,Phet=0.756）、显性模型（OR=1.67,95%CI：1.39～1.99,Phet=0.082）和隐性模型（OR=1.35,95%CI：1.19～1.55,Phet=0.000）,差异均有统计学意义。在基因型与体质指数（body mass index,BMI）Z-score定量关联性分析中,发现rs17782313T〉C的突变会影响儿童的BMI Z-score（WMD=0.14,95%CI：0.06～0.23,CC vs TT）。结论Meta分析研究结果证实了MC4R rs17782313与儿童肥胖的关系。
基金the National Natural Science Foundation of China (30470814 to Wei-Ping JIA)
文摘Objective To investigate how F261S mutation identified from Chinese obese patients affects the function of melanocorfin 4 receptor (MC4R) and to analyze the obesity-related phenotypes in subjects carrying the F261S mutation. Methods F261S mutant of MC4R was generated by site-directed mutagenesis. Plasmids encoding wild-type or F261S mutant of MC4R were transfected into HEK293 and COS-7 cells to examine their functional characteristics. Signaling properties of F261S MC4R were assessed by measuring intracellular cAMP levels in response to α-MSH stimulation. Cell surface expression of F261S MC4R was compared with that of wild-type MC4R. Clinical examinations were performed in subjects carrying F261S mutation and in non-mutated controls. Results The a-MSH-stimulated reporter gene activity was significantly reduced in cells expressing F261S MC4R, with a maximal response equal to 57% of wild-type MC4R. The F261S mutation also led to a significant change in the EC50 value compared with the wild-type receptor (P〈0.01). Immunofluorescent assay revealed a marked reduction in plasma membrane localization of the MC4R in cells expressing the F261S mutant receptor. The resting metabolic rate and fat composition of the mutant carriers were not significantly different from those of the non-mutated obese controls. Conclusions The decreased response to α-MSH due to the intracellular retention of MC4R may cause early-onset obesity in the F261S pedigree of Chinese.
