Maternal high-fat diet activates hepatic interleukin-4 in rat male offspring accompanied by increased eosinophil infiltration

Huan Wang, Guanying Bianca Xu, Hong Chen, Yuan Xiang Pan

Research output: Contribution to journalArticlepeer-review


Interleukin-4 (IL-4) 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 IL-4 in a maternal HF diet model in the liver of adult offspring. Timed-pregnant Sprague-Dawley rats were fed either control (C) 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 wk of age, followed by histological and molecular analysis to investigate the maternal programming effects on IL-4 by HF diet. Maternal HF diet significantly induced mRNA expression and protein level of IL-4 and promoted hypomethylation of Il4 compared with the control group. Methylation-selective PCR (MSP) confirmed that maternal HF diet increased RNA polymerase II, acetylation of histone H4, and dimethylation of histone 3 lysine 4 at the 6 kb region of Il4. Moreover, the rat eosinophil marker Siglec-F was increased and colocalized with IL-4 in the liver. In conclusion, our study indicated that IL-4 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 region of the 30 downstream region as well as an induced immune cell infiltration, especially eosinophil infiltration, in the liver of offspring.

Original languageEnglish (US)
Pages (from-to)G81-G92
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Issue number1
Early online dateOct 28 2020
StatePublished - Jan 2021


  • DNA methylation
  • Hepatocytes
  • Histone modification
  • Immune cell infiltration
  • Maternal diet

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology (medical)
  • Physiology
  • Hepatology


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