Maternal High Fat Diet Activates Hepatic Interleukin 4 in Rat Male Offspring Accompanied by Increased Eosinophil Infiltration.

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.