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Metabolomics Reveals Aryl Hydrocarbon Receptor Activation Induces Liver and Mammary Gland Metabolic Dysfunction in Lactating Mice

文献类型：期刊论文

作者Belton, Kerry R.2; Tian, Yuan1,2; Zhang, Limin1,2; Anitha, Mallappa2; Smith, Philip B.3; Perdew, Gary H.2; Patterson, Andrew D.2
刊名JOURNAL OF PROTEOME RESEARCH
出版日期2018-04-01
卷号17期号:4页码:1375-1382
关键词Aryl Hydrocarbon Receptor Metabolomics Lactation
ISSN号1535-3893
DOI10.1021/acs.jproteome.7b00709
文献子类Article
英文摘要The liver and the mammary gland have complementary metabolic roles during lactation. Substrates synthesized by the liver are released into the circulation and are taken up by the mammary gland for milk production. The aryl hydrocarbon receptor (AHR) has been identified as a lactation regulator in mice, and its activation has been associated with myriad morphological, molecular, and functional defects such as stunted gland development, decreased milk production, and changes in gene expression. In this study, we identified adverse metabolic changes in the lactation network (mammary, liver, and serum) associated with AHR activation using H-1 nuclear magnetic resonance (NMR)-based metabolomics. Pregnant mice expressing Ahr(d) (low affinity) or Ahr(b) (high affinity) were fed diets containing beta naphthoflavone (BNF), a potent AHR agonist. Mammary, serum, and liver metabolomics analysis identified significant changes in lipid and TCA cycle intermediates in the Ahr(b) mice. We observed decreased amino acid and glucose levels in the mammary gland extracts of Ahrb mice fed BNF. The serum of BNF fed Ahr(b) mice had significant changes in LDL/VLDL (increased) and HDL, PC, and GPC (decreased). Quantitative PCR analysis revealed, similar to 50% reduction in the expression of key lactogenesis mammary genes induding whey acid protein, alpha-lactalbumin, and beta-casein. We also observed morphologic and developmental disruptions in the mammary gland that are consistent with previous reports. Our observations support that AHR activity contributes to metabolism regulation in the lactation network.
WOS关键词GLUCOSE TRANSPORTERS ; GENE-EXPRESSION ; CELL-LINE ; IN-VITRO ; DIFFERENTIATION ; EXPOSURE ; DIOXIN ; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN ; IDENTIFICATION ; AFFINITY
WOS研究方向Biochemistry & Molecular Biology
语种英语
WOS记录号WOS:000429886600005
出版者AMER CHEMICAL SOC
资助机构Training in Animal Models of Inflammation National Institute of Allergy and Infectious Disease award(T32AI074551) ; Training in Animal Models of Inflammation National Institute of Allergy and Infectious Disease award(T32AI074551) ; Huck dissertation research award ; Huck dissertation research award ; Bill and Melinda Gates Foundation ; Bill and Melinda Gates Foundation ; National Institute of General Medical Sciences NIGMS(2R25GM078675-09A1) ; National Institute of General Medical Sciences NIGMS(2R25GM078675-09A1) ; National Institute of Environmental Health Sciences(ES004869 ; National Institute of Environmental Health Sciences(ES004869 ; ES022186 ; ES022186 ; ES026684 ; ES026684 ; ES028244) ; ES028244) ; Training in Animal Models of Inflammation National Institute of Allergy and Infectious Disease award(T32AI074551) ; Training in Animal Models of Inflammation National Institute of Allergy and Infectious Disease award(T32AI074551) ; Huck dissertation research award ; Huck dissertation research award ; Bill and Melinda Gates Foundation ; Bill and Melinda Gates Foundation ; National Institute of General Medical Sciences NIGMS(2R25GM078675-09A1) ; National Institute of General Medical Sciences NIGMS(2R25GM078675-09A1) ; National Institute of Environmental Health Sciences(ES004869 ; National Institute of Environmental Health Sciences(ES004869 ; ES022186 ; ES022186 ; ES026684 ; ES026684 ; ES028244) ; ES028244) ; Training in Animal Models of Inflammation National Institute of Allergy and Infectious Disease award(T32AI074551) ; Training in Animal Models of Inflammation National Institute of Allergy and Infectious Disease award(T32AI074551) ; Huck dissertation research award ; Huck dissertation research award ; Bill and Melinda Gates Foundation ; Bill and Melinda Gates Foundation ; National Institute of General Medical Sciences NIGMS(2R25GM078675-09A1) ; National Institute of General Medical Sciences NIGMS(2R25GM078675-09A1) ; National Institute of Environmental Health Sciences(ES004869 ; National Institute of Environmental Health Sciences(ES004869 ; ES022186 ; ES022186 ; ES026684 ; ES026684 ; ES028244) ; ES028244) ; Training in Animal Models of Inflammation National Institute of Allergy and Infectious Disease award(T32AI074551) ; Training in Animal Models of Inflammation National Institute of Allergy and Infectious Disease award(T32AI074551) ; Huck dissertation research award ; Huck dissertation research award ; Bill and Melinda Gates Foundation ; Bill and Melinda Gates Foundation ; National Institute of General Medical Sciences NIGMS(2R25GM078675-09A1) ; National Institute of General Medical Sciences NIGMS(2R25GM078675-09A1) ; National Institute of Environmental Health Sciences(ES004869 ; National Institute of Environmental Health Sciences(ES004869 ; ES022186 ; ES022186 ; ES026684 ; ES026684 ; ES028244) ; ES028244)
源URL[http://ir.wipm.ac.cn/handle/112942/12970]  
专题中国科学院武汉物理与数学研究所
通讯作者Patterson, Andrew D.
作者单位1.Univ Chinese Acad Sci, CAS Key Lab Magnet Resonance Biol Syst, State Key Lab Magnet Resonance & Atom & Mol Phys, Natl Ctr Magnet Resonance Wuhan,Wuhan Inst Phys &, Wuhan 430071, Hubei, Peoples R China
2.Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, Dept Vet & Biomed Sci, University Pk, PA 16802 USA
3.Penn State Univ, Metabol Facil, University Pk, PA 16802 USA
推荐引用方式
GB/T 7714		 Belton, Kerry R.,Tian, Yuan,Zhang, Limin,et al. Metabolomics Reveals Aryl Hydrocarbon Receptor Activation Induces Liver and Mammary Gland Metabolic Dysfunction in Lactating Mice[J]. JOURNAL OF PROTEOME RESEARCH,2018,17(4):1375-1382.
APA Belton, Kerry R..,Tian, Yuan.,Zhang, Limin.,Anitha, Mallappa.,Smith, Philip B..,...&Patterson, Andrew D..(2018).Metabolomics Reveals Aryl Hydrocarbon Receptor Activation Induces Liver and Mammary Gland Metabolic Dysfunction in Lactating Mice.JOURNAL OF PROTEOME RESEARCH,17(4),1375-1382.
MLA Belton, Kerry R.,et al."Metabolomics Reveals Aryl Hydrocarbon Receptor Activation Induces Liver and Mammary Gland Metabolic Dysfunction in Lactating Mice".JOURNAL OF PROTEOME RESEARCH 17.4(2018):1375-1382.

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来源：武汉物理与数学研究所

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