Omeprazole, an inhibitor of proton pump, suppresses De novo lipogenesis in gastric epithelial cells - 27/10/20

Doi : 10.1016/j.biopha.2020.110472

Peiyu Chen ^a,^b,^{^{1
These authors contributed equally to this work.}}, Linkai Li ^c,^{^{1
These authors contributed equally to this work.}}, Hongli Wang ^b,^{^{1
These authors contributed equally to this work.}}, Junhong Zhao ^b, Yang Cheng ^b, Jing Xie ^b, Meiwan Cao ^b, Ling Huang ^b, Fangying Yang ^b, Huan Chen ^b, Jiayu Chen ^d, Mingmin Su ^e, Yuxin Xu ^f, Fengfeng Zheng ^g, Lanlan Geng ^b,^h,^{^{2
These authors are co-responding authors.}}, Wanfu Xu ^b,^h,⁎, ^{^{2
These authors are co-responding authors.}} , Sitang Gong ^a,^b,^h,⁎, ^{^{2
These authors are co-responding authors.}}
^a The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
^b Department of Gastroenterology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China
^c Department of Pharmacy, Zhuhai Center for Maternal and Child Health Care, Zhuhai, China
^d Department of Neonatal Intensive Care Unit, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China
^e Department of Cancer Biology and Therapeutics, School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Wales, CF103AT, UK
^f Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou, China
^g Department of Infectious Diseases, The Affiliated Hospital of Putian University, Putian, China
^h Guangzhou Women and Children’s Medical Center, Guangzhou Institute of Pediatrics, Guangzhou Medical University, Guangzhou, China

^⁎Corresponding authors at: Department of Gastroenterology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, 510623, China.Department of GastroenterologyGuangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangzhou510623China

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Highlights

•	Omeprazole suppressed FASN and ACLY expression, leading to attenuate lipid content.
•	Neither clarithromycin nor amoxicillin has no effect on FASN and ACLY expression.
•	FASN and ACLY expression were increased in H. pylori infectious gastric tissue.

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Abstract

Background

De novo lipogenesis (DNL) has been reported to involve in a serial types of disease. A standard triple therapy, including a PPI, omeprazole, and antibiotics (clarithromycin and amoxicillin), is widely used as the first-line regimen for helicobacter pylori (H. pylori)-infectious treatment. The objective of this study is to explore the function of a standard triple therapy on DNL.

Methods and results

We collected the clinical sample from the patients diagnosed with or without H. pylori infection. Oil red staining, real-time PCR, western blotting (WB) and adipored experiment were performed to detect the effect of a standard triple therapy on DNL. The expression of relative key enzymes was assessed in gastric mucosa of clinical sample by IHC. Both 54 cases with H. pylori-negative and 37 cases with H. pylori-positive were enrolled in this study, and IHC assay showed that both fatty acid synthase (FASN) and ATP-citrate lyase (ACLY) expression, the critical enzymes involved in DNL, were increased in gastric mucosa of patients with H. pylori-positive compared with that with H. pylori-negative. Real-time PCR and WB analysis showed that neither clarithromycin nor amoxicillin inhibited FASN and ACLY expression, while treatment of BGC823 cells with omeprazole with 200 μM or 300 μM significantly abolished FASN and ACLY expression, leading to reduce lipid content.

Conclusion

These findings suggested that omeprazole suppressed DNL in gastric cells, implying that targeting DNL is an alternative strategy in improving the treatment of patients with H. pylori infection.

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Abbreviations : ACLY, ACC, AMPK, DNL, FASN, HDAC3, IDH, MALT, PPARγ, PPI, SREBP-1, SPOT14, TCA

Keywords : Helicobacter pylori, Omeprazole, De novo lipogenesis, Lipid content

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Omeprazole, an inhibitor of proton pump, suppresses De novo lipogenesis in gastric epithelial cells - 27/10/20

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