Intestinal Atp8b1 Dysfunction Causes Hepatic Choline Deficiency and Steatohepatitis

Overview

Journal Nat Commun

Specialty Biology

Date 2023 Nov 22

PMID 37990006

Authors

Ryutaro Tamura

Yusuke Sabu

Tadahaya Mizuno

Seiya Mizuno

Satoshi Nakano

Mitsuyoshi Suzuki

Daiki Abukawa

Shunsaku Kaji

Yoshihiro Azuma

Ayano Inui

Tatsuya Okamoto

Seiichi Shimizu

Akinari Fukuda

Seisuke Sakamoto

Mureo Kasahara

Satoru Takahashi

Hiroyuki Kusuhara

Yoh Zen

Tomohiro Ando

Hisamitsu Hayashi

Affiliations

Soon will be listed here.

Abstract

Choline is an essential nutrient, and its deficiency causes steatohepatitis. Dietary phosphatidylcholine (PC) is digested into lysoPC (LPC), glycerophosphocholine, and choline in the intestinal lumen and is the primary source of systemic choline. However, the major PC metabolites absorbed in the intestinal tract remain unidentified. ATP8B1 is a P4-ATPase phospholipid flippase expressed in the apical membrane of the epithelium. Here, we use intestinal epithelial cell (IEC)-specific Atp8b1-knockout (Atp8b1) mice. These mice progress to steatohepatitis by 4 weeks. Metabolomic analysis and cell-based assays show that loss of Atp8b1 in IEC causes LPC malabsorption and thereby hepatic choline deficiency. Feeding choline-supplemented diets to lactating mice achieves complete recovery from steatohepatitis in Atp8b1 mice. Analysis of samples from pediatric patients with ATP8B1 deficiency suggests its translational potential. This study indicates that Atp8b1 regulates hepatic choline levels through intestinal LPC absorption, encouraging the evaluation of choline supplementation therapy for steatohepatitis caused by ATP8B1 dysfunction.

Citing Articles

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Shin H, Takatsu H Commun Biol. 2025; 8(1):135.

PMID: 39875509 PMC: 11775268. DOI: 10.1038/s42003-025-07549-3.

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