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Int. J. Mol. Sci. 2016, 17(10), 1610; doi:10.3390/ijms17101610

Prenatal Dexamethasone and Postnatal High-Fat Diet Decrease Interferon Gamma Production through an Age-Dependent Histone Modification in Male Sprague-Dawley Rats

Department of Pediatrics, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Graduate Institute of Clinical Medical Science, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
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Academic Editor: Charles J. Malemud
Received: 1 July 2016 / Revised: 11 September 2016 / Accepted: 14 September 2016 / Published: 22 September 2016
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

Overexposure to prenatal glucocorticoid (GC) disturbs hypothalamic-pituitary-adrenocortical axis-associated neuroendocrine metabolism and susceptibility to metabolic syndrome. A high-fat (HF) diet is a major environmental factor that can cause metabolic syndrome. We aimed to investigate whether prenatal GC plus a postnatal HF diet could alter immune programming in rat offspring. Pregnant Sprague-Dawley rats were given intraperitoneal injections of dexamethasone or saline at 14–21 days of gestation. Male offspring were then divided into four groups: vehicle, prenatal dexamethasone exposure, postnatal HF diet (VHF), and prenatal dexamethasone exposure plus a postnatal HF diet (DHF). The rats were sacrificed and adaptive immune function was evaluated. Compared to the vehicle, the DHF group had lower interferon gamma (IFN-γ) production by splenocytes at postnatal day 120. Decreases in H3K9 acetylation and H3K36me3 levels at the IFN-γ promoter correlated with decreased IFN-γ production. The impaired IFN-γ production and aberrant site-specific histone modification at the IFN-γ promoter by prenatal dexamethasone treatment plus a postnatal HF diet resulted in resilience at postnatal day 180. Prenatal dexamethasone and a postnatal HF diet decreased IFN-γ production through a site-specific and an age-dependent histone modification. These findings suggest a mechanism by which prenatal exposure to GC and a postnatal environment exert effects on fetal immunity programming. View Full-Text
Keywords: prenatal glucocorticoid; high-fat diet; IFN-γ; histone modification; age-dependent prenatal glucocorticoid; high-fat diet; IFN-γ; histone modification; age-dependent
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Yu, H.-R.; Tain, Y.-L.; Sheen, J.-M.; Tiao, M.-M.; Chen, C.-C.; Kuo, H.-C.; Hung, P.-L.; Hsieh, K.-S.; Huang, L.-T. Prenatal Dexamethasone and Postnatal High-Fat Diet Decrease Interferon Gamma Production through an Age-Dependent Histone Modification in Male Sprague-Dawley Rats. Int. J. Mol. Sci. 2016, 17, 1610.

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