World J Gastroenterol. Jan 14, 2027; 33(2): 125044 Published online Jan 14, 2027. doi: 10.3748/wjg.125044
Lauric acid attenuates 14-day DDC-induced cholangiopathy in association with reduced NF-κB-CCL2 signaling and restored LRH-1-regulated gene expression
Swati Ghosh, Michael W Devereaux, Colin C Anderson, David J Orlicky, Ronald J Sokol
Swati Ghosh, Michael W Devereaux, Ronald J Sokol, Section of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Colorado Anschutz School of Medicine, Aurora, CO 80045, United States
Colin C Anderson, Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz School of Medicine, Aurora, CO 80045, United States
David J Orlicky, Department of Pathology, University of Colorado Anschutz School of Medicine, Aurora, CO 80045, United States
Ronald J Sokol, Pediatric Liver Center, Digestive Health Institute, Children’s Hospital Colorado, Aurora, CO 80045, United States
Author contributions: Ghosh S conceived and designed the study, performed most experiments, analyzed and managed the data, wrote the manuscript and obtained funding; Devereaux MW performed mouse care and experiments; Anderson CC performed liquid chromatography-mass spectrometry analyses; Orlicky DJ analyzed histology; Ghosh S and Sokol RJ critically revised the manuscript; all authors read and approved the final manuscript.
AI contribution statement: No AI tool was used except generation of Figure 4I. Figure 4I was created using BioRender.
Supported by the Childhood Liver Disease Research Network (NIDDK, NIH), No. U01DK062453.
Institutional animal care and use committee statement: All animal experiments were reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) at the University of Colorado Anschutz Medical Campus.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: Data will be made available on reasonable request.
Corresponding author: Swati Ghosh, PhD, Principal Investigator, Section of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Colorado Anschutz School of Medicine, 12700 East 19th Avenue, Aurora, CO 80045, United States. swati.ghosh@cuanschutz.edu
Received: June 30, 2026 Revised: July 30, 2026 Accepted: September 29, 2026 Published online: January 14, 2027 Processing time: 131 Days and 14.4 Hours
Core Tip
Core Tip: Lauric acid (LA), a dietary medium-chain fatty acid, was studied in a 14-day 3,5-diethoxycarbonyl-1,4-dihydrocollidine-induced mouse model. Concurrent 5% LA supplementation attenuated biochemical cholestasis, hepatocellular injury, ductular reaction, collagen deposition, oxidative stress, senescence, and cell-death markers. These effects were associated with reduced nuclear factor-kappa B - C-C motif chemokine ligand 2 signaling, restored liver receptor homolog-1-regulated gene expression, and increased hepatic dilauroylphosphatidylcholine abundance. This study demonstrates a decrease in the development of liver injury but was not designed to demonstrate reversal of established liver injury. Further investigation will be needed to determine if liver receptor homolog-1 or dilauroylphosphatidylcholine is required for LA protection in this model.