Maternal high-fat diet modulates the fetal thyroid axis and thyroid gene expression in a nonhuman primate model

Melissa A. Suter, Haleh Sangi-Haghpeykar, Lori Showalter, Cynthia Shope, Min Hu, Kathleen Brown, Sarah Williams, R. Alan Harris, Kevin Grove, Robert H. Lane, Kjersti M. Aagaard

    Research output: Contribution to journalArticle

    30 Citations (Scopus)

    Abstract

    Thyroid hormone (TH) is an essential regulator of both fetal development and energy homeostasis. Although the association between subclinical hypothyroidism and obesity has been well studied, a causal relationship has yet to be established. Using our well-characterized nonhuman primate model of excess nutrition, we sought to investigate whether maternal high-fat diet (HFD)-induced changes in TH homeostasis may underlie later in life development of metabolic disorders and obesity. Here, we show that in utero exposure to a maternal HFD is associated with alterations of the fetal thyroid axis. At the beginning of the third trimester, fetal free T4 levels are significantly decreased with HFD exposure compared with those of control diet-exposed offspring. Furthermore, transcription of the deiodinase, iodothyronine (DIO) genes, which help maintain thyroid homeostasis, are significantly (P = 0.05) disrupted in the fetal liver, thyroid, and hypothalamus. Genes involved in TH production are decreased (TRH, TSHR, TG, TPO, and SLC5A5) in hypothalamus and thyroid gland. In experiments designed to investigate the molecular underpinnings of these observations, we observe that the TH nuclear receptors and their downstream regulators are disrupted with maternal HFD exposure. In fetal liver, the expression of TH receptor β (THRB) is increased 1.9-fold (P = 0.012). Thorough analysis of the THRB promoter reveals a maternal diet-induced alteration in the fetal THRB histone code, alongside differential promoter occupancy of corepressors and coactivators. We speculate that maternal HFD exposure in utero may set the stage for later in life obesity through epigenomic modifications to the histone code, which modulates the fetal thyroid axis.

    Original languageEnglish (US)
    Pages (from-to)2071-2080
    Number of pages10
    JournalMolecular Endocrinology
    Volume26
    Issue number12
    DOIs
    StatePublished - Dec 1 2012

    Fingerprint

    High Fat Diet
    Primates
    Thyroid Gland
    Mothers
    Gene Expression
    Histone Code
    Thyroid Hormones
    Thyroid Hormone Receptors
    Homeostasis
    Obesity
    Hypothalamus
    Diet
    Co-Repressor Proteins
    Iodide Peroxidase
    Liver
    Third Pregnancy Trimester
    Cytoplasmic and Nuclear Receptors
    Fetal Development
    Hypothyroidism
    Epigenomics

    ASJC Scopus subject areas

    • Molecular Biology
    • Endocrinology

    Cite this

    Suter, M. A., Sangi-Haghpeykar, H., Showalter, L., Shope, C., Hu, M., Brown, K., ... Aagaard, K. M. (2012). Maternal high-fat diet modulates the fetal thyroid axis and thyroid gene expression in a nonhuman primate model. Molecular Endocrinology, 26(12), 2071-2080. https://doi.org/10.1210/me.2012-1214

    Maternal high-fat diet modulates the fetal thyroid axis and thyroid gene expression in a nonhuman primate model. / Suter, Melissa A.; Sangi-Haghpeykar, Haleh; Showalter, Lori; Shope, Cynthia; Hu, Min; Brown, Kathleen; Williams, Sarah; Alan Harris, R.; Grove, Kevin; Lane, Robert H.; Aagaard, Kjersti M.

    In: Molecular Endocrinology, Vol. 26, No. 12, 01.12.2012, p. 2071-2080.

    Research output: Contribution to journalArticle

    Suter, MA, Sangi-Haghpeykar, H, Showalter, L, Shope, C, Hu, M, Brown, K, Williams, S, Alan Harris, R, Grove, K, Lane, RH & Aagaard, KM 2012, 'Maternal high-fat diet modulates the fetal thyroid axis and thyroid gene expression in a nonhuman primate model', Molecular Endocrinology, vol. 26, no. 12, pp. 2071-2080. https://doi.org/10.1210/me.2012-1214
    Suter, Melissa A. ; Sangi-Haghpeykar, Haleh ; Showalter, Lori ; Shope, Cynthia ; Hu, Min ; Brown, Kathleen ; Williams, Sarah ; Alan Harris, R. ; Grove, Kevin ; Lane, Robert H. ; Aagaard, Kjersti M. / Maternal high-fat diet modulates the fetal thyroid axis and thyroid gene expression in a nonhuman primate model. In: Molecular Endocrinology. 2012 ; Vol. 26, No. 12. pp. 2071-2080.
    @article{85e25d860a9e4eee96e24fbffa728fce,
    title = "Maternal high-fat diet modulates the fetal thyroid axis and thyroid gene expression in a nonhuman primate model",
    abstract = "Thyroid hormone (TH) is an essential regulator of both fetal development and energy homeostasis. Although the association between subclinical hypothyroidism and obesity has been well studied, a causal relationship has yet to be established. Using our well-characterized nonhuman primate model of excess nutrition, we sought to investigate whether maternal high-fat diet (HFD)-induced changes in TH homeostasis may underlie later in life development of metabolic disorders and obesity. Here, we show that in utero exposure to a maternal HFD is associated with alterations of the fetal thyroid axis. At the beginning of the third trimester, fetal free T4 levels are significantly decreased with HFD exposure compared with those of control diet-exposed offspring. Furthermore, transcription of the deiodinase, iodothyronine (DIO) genes, which help maintain thyroid homeostasis, are significantly (P = 0.05) disrupted in the fetal liver, thyroid, and hypothalamus. Genes involved in TH production are decreased (TRH, TSHR, TG, TPO, and SLC5A5) in hypothalamus and thyroid gland. In experiments designed to investigate the molecular underpinnings of these observations, we observe that the TH nuclear receptors and their downstream regulators are disrupted with maternal HFD exposure. In fetal liver, the expression of TH receptor β (THRB) is increased 1.9-fold (P = 0.012). Thorough analysis of the THRB promoter reveals a maternal diet-induced alteration in the fetal THRB histone code, alongside differential promoter occupancy of corepressors and coactivators. We speculate that maternal HFD exposure in utero may set the stage for later in life obesity through epigenomic modifications to the histone code, which modulates the fetal thyroid axis.",
    author = "Suter, {Melissa A.} and Haleh Sangi-Haghpeykar and Lori Showalter and Cynthia Shope and Min Hu and Kathleen Brown and Sarah Williams and {Alan Harris}, R. and Kevin Grove and Lane, {Robert H.} and Aagaard, {Kjersti M.}",
    year = "2012",
    month = "12",
    day = "1",
    doi = "10.1210/me.2012-1214",
    language = "English (US)",
    volume = "26",
    pages = "2071--2080",
    journal = "Molecular Endocrinology",
    issn = "0888-8809",
    publisher = "The Endocrine Society",
    number = "12",

    }

    TY - JOUR

    T1 - Maternal high-fat diet modulates the fetal thyroid axis and thyroid gene expression in a nonhuman primate model

    AU - Suter, Melissa A.

    AU - Sangi-Haghpeykar, Haleh

    AU - Showalter, Lori

    AU - Shope, Cynthia

    AU - Hu, Min

    AU - Brown, Kathleen

    AU - Williams, Sarah

    AU - Alan Harris, R.

    AU - Grove, Kevin

    AU - Lane, Robert H.

    AU - Aagaard, Kjersti M.

    PY - 2012/12/1

    Y1 - 2012/12/1

    N2 - Thyroid hormone (TH) is an essential regulator of both fetal development and energy homeostasis. Although the association between subclinical hypothyroidism and obesity has been well studied, a causal relationship has yet to be established. Using our well-characterized nonhuman primate model of excess nutrition, we sought to investigate whether maternal high-fat diet (HFD)-induced changes in TH homeostasis may underlie later in life development of metabolic disorders and obesity. Here, we show that in utero exposure to a maternal HFD is associated with alterations of the fetal thyroid axis. At the beginning of the third trimester, fetal free T4 levels are significantly decreased with HFD exposure compared with those of control diet-exposed offspring. Furthermore, transcription of the deiodinase, iodothyronine (DIO) genes, which help maintain thyroid homeostasis, are significantly (P = 0.05) disrupted in the fetal liver, thyroid, and hypothalamus. Genes involved in TH production are decreased (TRH, TSHR, TG, TPO, and SLC5A5) in hypothalamus and thyroid gland. In experiments designed to investigate the molecular underpinnings of these observations, we observe that the TH nuclear receptors and their downstream regulators are disrupted with maternal HFD exposure. In fetal liver, the expression of TH receptor β (THRB) is increased 1.9-fold (P = 0.012). Thorough analysis of the THRB promoter reveals a maternal diet-induced alteration in the fetal THRB histone code, alongside differential promoter occupancy of corepressors and coactivators. We speculate that maternal HFD exposure in utero may set the stage for later in life obesity through epigenomic modifications to the histone code, which modulates the fetal thyroid axis.

    AB - Thyroid hormone (TH) is an essential regulator of both fetal development and energy homeostasis. Although the association between subclinical hypothyroidism and obesity has been well studied, a causal relationship has yet to be established. Using our well-characterized nonhuman primate model of excess nutrition, we sought to investigate whether maternal high-fat diet (HFD)-induced changes in TH homeostasis may underlie later in life development of metabolic disorders and obesity. Here, we show that in utero exposure to a maternal HFD is associated with alterations of the fetal thyroid axis. At the beginning of the third trimester, fetal free T4 levels are significantly decreased with HFD exposure compared with those of control diet-exposed offspring. Furthermore, transcription of the deiodinase, iodothyronine (DIO) genes, which help maintain thyroid homeostasis, are significantly (P = 0.05) disrupted in the fetal liver, thyroid, and hypothalamus. Genes involved in TH production are decreased (TRH, TSHR, TG, TPO, and SLC5A5) in hypothalamus and thyroid gland. In experiments designed to investigate the molecular underpinnings of these observations, we observe that the TH nuclear receptors and their downstream regulators are disrupted with maternal HFD exposure. In fetal liver, the expression of TH receptor β (THRB) is increased 1.9-fold (P = 0.012). Thorough analysis of the THRB promoter reveals a maternal diet-induced alteration in the fetal THRB histone code, alongside differential promoter occupancy of corepressors and coactivators. We speculate that maternal HFD exposure in utero may set the stage for later in life obesity through epigenomic modifications to the histone code, which modulates the fetal thyroid axis.

    UR - http://www.scopus.com/inward/record.url?scp=84870387080&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=84870387080&partnerID=8YFLogxK

    U2 - 10.1210/me.2012-1214

    DO - 10.1210/me.2012-1214

    M3 - Article

    C2 - 23015752

    AN - SCOPUS:84870387080

    VL - 26

    SP - 2071

    EP - 2080

    JO - Molecular Endocrinology

    JF - Molecular Endocrinology

    SN - 0888-8809

    IS - 12

    ER -