SinoXivLactose Stimulation of Hepatic De Novo Lipogenesis Implicates Non-Canonical Pathways of Galactose Metabolism: A Randomised Crossover Trial
Abstract
Dietary sugars differentially influence hepatic lipid metabolism, yet the metabolism of galactose—the monosaccharide unique to lactose—remains poorly defined in humans. Here, using stable isotope tracers and lipoprotein fractionation in a randomized crossover trial, we show that lactose ingestion robustly stimulates hepatic de novo lipogenesis and exaggerates postprandial lipaemia to an extent comparable with sucrose and markedly greater than a glucose polymer. Lactose-induced lipaemia arises from coordinated increases in endogenous, dietary and newly synthesized fatty acids and is associated with elevated lactate production but not fructose-associated uric acid accumulation. Strikingly, the magnitude of lactose-stimulated lipogenesis is inversely related to postprandial glycaemia, and modest galactose co-ingestion attenuates glycaemic responses to a starch meal. These findings reveal non-canonical pathways of galactose metabolism that couple lipogenesis to reduced glycaemic exposure and challenge the prevailing view that galactose-containing sugars are metabolically equivalent to glucose-based carbohydrates.
Citation Information
@article{javiergonzalez2026,
title={Lactose Stimulation of Hepatic De Novo Lipogenesis Implicates Non-Canonical Pathways of Galactose Metabolism: A Randomised Crossover Trial},
author={Javier Gonzalez and Steven Carter and Bruno Spellanzon and Elspeth Johnson and Francoise Koumanov and Kaitlyn Dennis and Coco Taylor Start and Louise Bradshaw and Alfonso Moreno-Cabañas and Lucy Merrell and Emma Vincent and Benedita Deslandes and Jennifer Maher and Matt Neville and James Betts and Dylan Thompson and Leanne Hodson},
journal={Nature Portfolio},
year={2026},
doi={https://doi.org/10.21203/rs.3.rs-9346481/v1}
}
