Lasting Effects on Body Weight

Lasting Effects on Body Weight

11 Pages · 2013 · 618 KB · English

C.B. was supported on a fellowship from NIH grant R25 CA044789, National Cancer Institute (http://www.cancer.gov) Additional support is acknowledged from . metabolism. Examples are oxidative phosphorylation, citrate cycle, fatty acid metabolism, oxidoreductase activity, and electron carrier activit

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Lasting Effects on Body Weight and Mammary Gland Gene Expression in Female Mice upon Early Life Exposure to n 3 but Not n 6 HighFat Diets Mirjam Luijten 1, Amar V Singh 2, Caleb A Bastian 2, Anja Westerman 1, M Michele Pisano 2, Jeroen L A Pennings 1, Aart Verhoef 1, Maia L Green 2, Aldert H Piersma 1, Annemieke de Vries 1, Thomas B Knudsen 2,3 * 1Laboratory for Health Protection Research, National Institute for Public Health and the Environment, Bilthoven, The Netherlands,2Department of Molecular, Cellular and Craniofacial Biology, University of Louisville Birth Defects Center, Louisville, Kentucky, United States of America,3National Center for Computational Toxicology, US Environmental Protection Agency, Research Triangle Park, North Carolina, United States of America Abstract Exposure to an imbalance of nutrients prior to conception and during critical developmental periods can have lasting consequences on physiological processes resulting in chronic diseases later in life Developmental programming has been shown to involve structural and functional changes in important tissues The aim of the present study was to investigate whether early life diet has a programming effect on the mammary gland Wildtype mice were exposed from 2 weeks prior to conception to 6 weeks of age to a regular lowfat diet, or to highfat diets based on either corn oil or flaxseed oil At 6 weeks of age, all mice were shifted to the regular lowfat diet until termination at 10 weeks of age Early life exposure to a highfat diet, either high inn6 (corn oil) or inn3 (flaxseed oil) polyunsaturated fatty acids, did not affect birth weight, but resulted in an increased body weight at 10 weeks of age Transcriptome analyses of the fourth abdominal mammary gland revealed differentially expressed genes between the different treatment groups Exposure to highfat diet based on flaxseed oil, but not on corn oil, resulted in regulation of pathways involved in energy metabolism, immune response and inflammation Our findings suggest that diet during early life indeed has a lasting effect on the mammary gland and significantly influences postnatal body weight gain, metabolic status, and signaling networks in the mammary gland of female offspring Citation:Luijten M, Singh AV, Bastian CA, Westerman A, Pisano MM, et al (2013) Lasting Effects on Body Weight and Mammary Gland Gene Expression in Female Mice upon Early Life Exposure ton3 but Notn6 HighFat Diets PLoS ONE 8(2): e55603 doi:101371/journalpone0055603 Editor:Aamir Ahmad, Wayne State University School of Medicine, United States of America ReceivedAugust 31, 2011;AcceptedJanuary 3, 2013;PublishedFebruary 7, 2013 This is an openaccess article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose The work is made available under the Creative Commons CC0 public domain dedication Funding:This research was supported by NIH grant R21 ES013821, National Institute of Environmental Health Sciences (http://wwwniehsnihgov) CB was supported on a fellowship from NIH grant R25 CA044789, National Cancer Institute (http://wwwcancergov) Additional support is acknowledged from Bioinformatics and Biostatistics Core, University of Louisville Center for Integrative Biology and Environmental Genomics, funded by NIH grant P30 ES014443, National Institute of Environmental Health Sciences (http://wwwniehsnihgov) The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript Competing Interests:The authors have declared that no competing interests exist * Email: [email protected] These authors contributed equally to this work Introduction Over the past decade, numerous epidemiological studies have shown strong inverse associations between birth weight and risk of cardiovascular disease, hypertension, type 2 diabetes, and other diseases in adult life [1–4] These findings have been largely supported by the results of studies in experimental animals [5,6] Barker and colleagues originally put forward the hypothesis that poor fetal growth results in an increased risk for coronary heart disease [7,8] The fetal origins of adult disease hypothesis or ‘Barker hypothesis’ states that adverse environ mental factors during fetal life, particularly nutrition, ‘program’ the individual for an increased risk of major chronic diseases [9–13] Studies on the Barker hypothesis have mainly focused on the impact

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