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DNA Methylation Suppresses Liver Hamp Expression in Response to Iron Deficiency After Bariatric Surgery

26 Pages Posted: 27 Jun 2019

See all articles by Yeping Huang

Yeping Huang

Shanghai Jiao Tong University (SJTU) - Shanghai Diabetes Institute

Hong Zhang

Shanghai Jiao Tong University (SJTU) - Shanghai Diabetes Institute

Haijun Liu

Shanghai Jiao Tong University (SJTU) - Shanghai Fengxian Central Hospital

Xiao Wang

Shanghai Jiao Tong University (SJTU) - Shanghai Diabetes Institute

Chen Wang

Shanghai Jiao Tong University (SJTU) - Sixth People's Hospital

Jianzhong Di

Shanghai Jiao Tong University (SJTU) - Sixth People's Hospital

Yuqian Bao

Shanghai Jiao Tong University (SJTU) - Department of Endocrinology and Metabolism

Rong Zhang

Shanghai Jiao Tong University (SJTU) - Shanghai Key Laboratory of Diabetes Mellitus

Weiping Jia

Shanghai Jiao Tong University (SJTU) - Shanghai Key Laboratory of Diabetes Mellitus

Xueli Zhang

Shanghai Jiao Tong University (SJTU) - Shanghai Fengxian Central Hospital

Jian Zhou

Shanghai Jiao Tong University (SJTU) - Shanghai Diabetes Institute

Yao Li

Shanghai Jiao Tong University (SJTU) - School of Medicine

Cheng Hu

Shanghai Jiao Tong University (SJTU) - Shanghai Diabetes Institute; Shanghai Jiao Tong University (SJTU) - Shanghai Fengxian Central Hospital

More...

Abstract

Background: Iron deficiency is extremely common after bariatric surgery. HEPCIDIN, encoded by Hamp, is a hormone that negatively regulates iron homeostasis. We therefore aimed to investigate the alteration of Hamp expression and its related regulatory factors to explore the probable role of DNA methylation in regulating Hamp expression in the context of iron deficiency after bariatric surgery.

Methods: RNA-seq was performed using rat liver tissue after either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) surgery to identify differentially expressed genes (DEGs) between the bariatric surgery and sham group. Hamp expression were measured by quantitative PCR and ELISA, respectively. The DNA methylation level was determined using MassARRAY EpiTYPER. Iron status, erythrocyte parameters and inflammation factors were also assessed.

Results: RNA-seq data showed that Hamp expression in liver changed most dramatically in RYGB-operated rats. Both the mRNA expression of Hamp and the abundance of its protein product HEPCIDIN-25 were markedly decreased after bariatric surgery compared with sham, while SG-operated rats showed marginally higher Hamp expression than RYGB-operated rats. The DNA methylation level of the Hamp promoter region was significant higher in RYGB-operated rats than sham, while SG rats increased slightly in DNA methylation. Consistent with the change of HEPCIDIN-25, serum iron was significantly lower for both bariatric groups than sham and particularly low in RYGB.

Conclusions: Our data demonstrate that elevated DNA methylation of the Hamp promoter region suppresses its expression, and this epigenetic modification likely occurs in reaction to iron deficiency after bariatric surgery, helping to maintain system iron homeostasis.

Funding Statement: The current study was supported by grants from National Key R&D Program of China (2016YFC1304801), the Outstanding Academic Leaders of Shanghai Health System program (2017BR008), the Yangtze River Scholar program, the National Natural Science Foundation of China (81800708), and the Shanghai Sixth People’s Hospital (YNLC201725).

Declaration of Interests: The authors declare no competing financial interests.

Ethics Approval Statement: All animals were maintained and used in accordance with the guidelines of the Animal Care and Use Committee of Shanghai Sixth People’s Hospital.

Keywords: DNA methylation, Hamp, iron deficiency, Roux-en-Y gastric bypass, sleeve gastrectomy

Suggested Citation

Huang, Yeping and Zhang, Hong and Liu, Haijun and Wang, Xiao and Wang, Chen and Di, Jianzhong and Bao, Yuqian and Zhang, Rong and Jia, Weiping and Zhang, Xueli and Zhou, Jian and Li, Yao and Hu, Cheng, DNA Methylation Suppresses Liver Hamp Expression in Response to Iron Deficiency After Bariatric Surgery (June 24, 2019). Available at SSRN: https://ssrn.com/abstract=3409295 or http://dx.doi.org/10.2139/ssrn.3409295

Yeping Huang

Shanghai Jiao Tong University (SJTU) - Shanghai Diabetes Institute

China

Hong Zhang

Shanghai Jiao Tong University (SJTU) - Shanghai Diabetes Institute

China

Haijun Liu

Shanghai Jiao Tong University (SJTU) - Shanghai Fengxian Central Hospital

China

Xiao Wang

Shanghai Jiao Tong University (SJTU) - Shanghai Diabetes Institute

China

Chen Wang

Shanghai Jiao Tong University (SJTU) - Sixth People's Hospital

China

Jianzhong Di

Shanghai Jiao Tong University (SJTU) - Sixth People's Hospital

China

Yuqian Bao

Shanghai Jiao Tong University (SJTU) - Department of Endocrinology and Metabolism

China

Rong Zhang

Shanghai Jiao Tong University (SJTU) - Shanghai Key Laboratory of Diabetes Mellitus

China

Weiping Jia

Shanghai Jiao Tong University (SJTU) - Shanghai Key Laboratory of Diabetes Mellitus

China

Xueli Zhang

Shanghai Jiao Tong University (SJTU) - Shanghai Fengxian Central Hospital

China

Jian Zhou

Shanghai Jiao Tong University (SJTU) - Shanghai Diabetes Institute

China

Yao Li

Shanghai Jiao Tong University (SJTU) - School of Medicine

Shanghai
China

Cheng Hu (Contact Author)

Shanghai Jiao Tong University (SJTU) - Shanghai Diabetes Institute ( email )

China

Shanghai Jiao Tong University (SJTU) - Shanghai Fengxian Central Hospital ( email )

China

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