Interleukin-4 (IL4) is activated as an immune response during infection or tissue injury. Epigenetic programming of maternal high-fat (HF) diet has long-term effects in the offspring. In the present study, we investigated the epigenetic regulation of IL4 in a maternal HF diet model in the liver of adult offspring. Timed-pregnant Sprague-Dawley rats were fed either control or HF diet throughout gestation and lactation. Offspring were placed on a control diet after weaning, generating C/C and HF/C groups. The liver was collected at 12 weeks of age and followed by histological and molecular analysis to investigate the maternal programming effects of IL4 by HF diet. Maternal HF diet significantly induced mRNA expression and protein level of IL4 while promoted hypomethylation of Il4 comparing to the control group. Methylation-selective PCR (MSP) confirmed maternal HF diet increased RNA polymerase II, acetylation of histone H4, and dimethylation of Histone 3 lysine 4 at the +6kb region of Il4. Moreover, rat eosinophil marker, Siglec-F was increased and co-localized with IL4 in the liver. In conclusion, our study indicated that IL4 was increased in liver cells in response to maternal HF diet. This coincides with DNA hypomethylation in combination with chromatin remodeling at the +6 kb of the 3' downstream region, as well as an induced immune cell infiltration, especially eosinophil infiltration, in the liver of offspring.

中文翻译：

---

母体高脂饮食激活大鼠嗜酸性粒细胞浸润增加的雄性后代中的肝白介素4

白细胞介素4（IL4）在感染或组织损伤期间被激活为免疫应答。母亲高脂饮食的表观遗传学编程对后代具有长期影响。在本研究中，我们调查了成年后代肝脏中母体HF饮食模型中IL4的表观遗传调控。定时妊娠的Sprague-Dawley大鼠在整个妊娠和哺乳期都喂饲对照饮食或HF饮食。断奶后，将后代置于对照饮食中，产生C / C和HF / C组。在12周龄时收集肝脏，然后进行组织学和分子分析，以研究HF饮食对IL4的母体编程作用。与对照组相比，母体HF饮食显着诱导IL4的mRNA表达和蛋白质水平，同时促进IL4的低甲基化。甲基化选择性PCR（MSP）证实母亲HF饮食增加了RNA聚合酶II，组蛋白H4的乙酰化和组蛋白3赖氨酸4在Il4的+ 6kb区域的二甲基化。此外，大鼠嗜酸性粒细胞标志物Siglec-F增加并与IL4共同定位在肝脏中。总而言之，我们的研究表明，对孕妇HF饮食的反应，肝细胞中IL4水平升高。这与DNA低甲基化结合后代3'下游区域+6 kb处的染色质重塑以及后代肝脏中诱导的免疫细胞浸润，尤其是嗜酸性粒细胞浸润相吻合。总而言之，我们的研究表明，对孕妇HF饮食的反应，肝细胞中IL4水平升高。这与DNA低甲基化结合后代3'下游区域+6 kb处的染色质重塑以及后代肝脏中诱导的免疫细胞浸润，尤其是嗜酸性粒细胞浸润相吻合。总而言之，我们的研究表明，对孕妇HF饮食的反应，肝细胞中IL4水平升高。这与DNA低甲基化结合后代3'下游区域+6 kb处的染色质重塑以及后代肝脏中诱导的免疫细胞浸润，尤其是嗜酸性粒细胞浸润相吻合。