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

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.

Prenatal Dexamethasone Exposure Increases the Susceptibility to Autoimmunity in Offspring Rats by Epigenetic Programing of Glucocorticoid Receptor

“…This intergenerational transmission of the GC effects is mainly mediated by epigenetic mechanisms [2, 4, 5]. In animals, the effects of prenatal GC treatment on the development of the immune system have been evaluated in small series, which indicated that prenatal GC treatment may result in the alteration of inflammatory factors [6, 7], and thus contribute to the disturbance of immune system. However, reports about the mechanism linked prenatal GC exposure and autoimmunity are few.…”

Targeting viperin improves diet-induced glucose intolerance but not adipose tissue inflammation

“…These findings suggest that adipose type I IFN signaling protects against diet-induced metabolic dysfunction, though it mediates inflammatory responses. Another study reported that high-fat diet decreased IFN-γ production in rats [ 49 ]. As a target of IFNs family, viperin expression depends on the relative activity of IFN-β and IFN-γ.…”

Resveratrol intake during pregnancy and lactation re-programs adiposity and ameliorates leptin resistance in male progeny induced by maternal high-fat/high sucrose plus postnatal high-fat/high sucrose diets via fat metabolism regulation

“…Female rats received either a regular rat diet (Fwusow Taiwan Co., Ltd., Taichung, Taiwan; 52 g% carbohydrates, 23.5 g% protein, 4.5 g% fat, 10 g% ash, and 8 g% fiber) or an HFHS diet (D12331, Research Diets, Inc., New Brunswick, NJ, USA; 35.8 g% fat plus high sucrose [35.5 g% carbohydrate], and protein 23.0 g%) ad libitum for 8 weeks before mating and during gestation and lactation. Male SD rats were kept with female rats until mating was confirmed [36,40]. The size of the litter was normalized after delivery immediately to conform the amount of milk and maternal care equalized.…”

“…Progeny body weight (BW) was determined every month since birth to four-month-old. At four-month-old, the rat progeny was sacrificed under anesthesia of Zoletil (Zoletil® 50; Virbac corporation, Carros, France) and xylazine (Rompun®, Bayer, Leverkusen, Germany), and blood samples were obtained by cardiac puncture as previously reported [39][40][41]. Retroperitoneal, mesenteric, epididymal, and subcutaneous fats were collected to measure adipose tissue weight [41].…”

“…The threshold cycles (Ct) were determined with Light Cycler software (ver. 1.5.0) and the relative quantification of mRNA expression was evaluated by compared Ct [39][40][41]. The primer sequences used were provided in Supplementary Table 1.…”