Low-dose galactose rebalances HBP-mTORC1-SREBP-1c signaling to suppress hepatic lipogenesis and protect against early-stage alcohol-related liver disease

American Journal of Physiology-Gastrointestinal and Liver Physiology 2026 Open access

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Authors: Yanhui Li, Rui Guo, Yanyu Qian, Izabela Hawro, José Córdoba‐Chacón, Yuwei Jiang, Zhenyuan Song
DOI: 10.1152/ajpgi.00379.2025
Cited by: 0
References: 42

Abstract

This study demonstrates that low-dose galactose, a dairy-derived monosaccharide, regulates hepatic de novo lipogenesis (DNL) by selectively inhibiting glucose-induced DNL activation. Mechanistically, low-dose galactose suppresses hexosamine biosynthetic pathway (HBP) flux, protein O-GlcNAcylation, and mTORC1 signaling, thereby inhibiting SREBP-1c activation in a Leloir pathway-dependent manner. Notably, galactose supplementation prevented early-stage alcohol-related liver disease by attenuating hepatic HBP-O-GlcNAcylation-SREBP-1c signaling.

Fields of Study & Subjects

Diet Metabolism and Disease Lipid metabolism and biosynthesis Alcohol Consumption and Health Effects

Publication details

Journal / source
American Journal of Physiology-Gastrointestinal and Liver Physiology
Volume
330
Issue
2
Pages
G170–G188
Publication date
13 January 2026
Language
EN