期刊
JOURNAL OF PROTEOME RESEARCH
卷 17, 期 4, 页码 1375-1382出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jproteome.7b00709
关键词
aryl hydrocarbon receptor; metabolomics; lactation
资金
- Training in Animal Models of Inflammation National Institute of Allergy and Infectious Disease award [T32AI074551]
- Huck dissertation research award
- Bill and Melinda Gates Foundation
- National Institute of General Medical Sciences NIGMS [2R25GM078675-09A1]
- National Institute of Environmental Health Sciences [ES004869, ES022186, ES026684, ES028244]
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [R01ES022186, R35ES028244, R56ES026684, R01ES004869] Funding Source: NIH RePORTER
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.
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