Effects of obesogenic diet and estradiol on dorsal raphe gene expression in old female macaques

Cynthia Bethea, Kevin Mueller, Arubala Reddy, Steven Kohama, Henryk Urbanski

    Research output: Contribution to journalArticle

    1 Citation (Scopus)

    Abstract

    The beneficial effects of bioidentical ovarian steroid hormone therapy (HT) during the perimenopause are gaining recognition. However, the positive effects of estrogen (E) plus or minus progesterone (P) administration to ovariectomized (Ovx) lab animals were recognized in multiple systems for years before clinical trials could adequately duplicate the results. Moreover, very large numbers of women are often needed to find statistically significant results in clinical trials of HT; and there are still opposing results being published, especially in neural and cardiovascular systems. One of the obvious differences between human and animal studies is diet. Laboratory animals are fed a diet that is low in fat and refined sugar, but high in micronutrients. In the US, a large portion of the population eats what is known as a “western style diet” or WSD that provides calories from 36% fat, 44% carbohydrates (includes 18.5% sugars) and 18% protein. Unfortunately, obesity and diabetes have reached epidemic proportions and the percentage of obese women in clinical trials may be overlooked. We questioned whether WSD and obesity could decrease the positive neural effects of estradiol (E) in the serotonin system of old macaques that were surgically menopausal. Old ovo-hysterectomized female monkeys were fed WSD for 2.5 years, and treated with placebo, Immediate E (ImE) or Delayed E (DE). Compared to old Ovx macaques on primate chow and treated with placebo or E, the WSD-fed monkeys exhibited greater individual variance and blunted responses to E-treatment in the expression of genes related to serotonin neurotransmission, CRH components in the midbrain, synapse assembly, DNA repair, protein folding, ubiquitylation, transport and neurodegeneration. For many of the genes examined, transcript abundance was lower in WSD-fed than chow-fed monkeys. In summary, an obesogenic diet for 2.5 years in old surgically menopausal macaques blunted or increased variability in E-induced gene expression in the dorsal raphe. These results suggest that with regard to function and viability in the dorsal raphe, HT may not be as beneficial for obese women as normal weight women.

    Original languageEnglish (US)
    Article numbere0178788
    JournalPLoS One
    Volume12
    Issue number6
    DOIs
    StatePublished - Jun 1 2017

    Fingerprint

    Macaca
    Nutrition
    Gene expression
    estradiol
    Estradiol
    Diet
    Haplorhini
    Gene Expression
    gene expression
    Animals
    Clinical Trials
    monkeys
    Hormones
    clinical trials
    menopause
    Sugars
    Serotonin
    serotonin
    Obesity
    Genes

    ASJC Scopus subject areas

    • Medicine(all)
    • Biochemistry, Genetics and Molecular Biology(all)
    • Agricultural and Biological Sciences(all)

    Cite this

    Effects of obesogenic diet and estradiol on dorsal raphe gene expression in old female macaques. / Bethea, Cynthia; Mueller, Kevin; Reddy, Arubala; Kohama, Steven; Urbanski, Henryk.

    In: PLoS One, Vol. 12, No. 6, e0178788, 01.06.2017.

    Research output: Contribution to journalArticle

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    AU - Urbanski, Henryk

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