Work

2-Hydroxyoleic Acid Preserves Lipid Homeostasis and Epithelial Barrier Function in Experimental Colitis

Year: 2026

Type: article

Abstract: Disrupted membrane lipid homeostasis is implicated in epithelial barrier dysfunction and inflammatory signaling in ulcerative colitis. Associated lipid alterations include a reduced phosphatidylcholine-to-phosphatidylethanolamine (PC/PE) ratio and accumulation of lysophosphatidylcholine (LPC) and ceramide. Although oleic acid (OA) has shown protective effects in experimental colitis, its therapeutic utility is limited by rapid metabolic turnover. We therefore tested whether 2-hydroxyoleic acid (2-OHOA), a synthetic hydroxylated OA derivative with enhanced metabolic stability, protects against intestinal inflammatory injury. In IFN-γ/TNF-α-stimulated Caco-2 monolayers, 2-OHOA pretreatment preserved epithelial barrier function, attenuated the increase in membrane fluidity, and reduced STAT3 and NF-κB activation, whereas OA at the same concentration provided little protection. In a dextran sulfate sodium (DSS)-induced murine colitis model, 2-OHOA pretreatment attenuated weight loss, disease activity index, colon shortening, and reduced the spleen index and histological injury scores, whereas OA at the same dose had minimal effects. 2-OHOA also attenuated colonic induction of Il-1β, Il-6, and Tnf-α expression and partially preserved occludin protein levels. Lipidomic analysis showed attenuation of DSS-induced PC depletion, shifts in the PC/PE and LPC/PC ratios, and ceramide and hexosylceramide accumulation. In cytokine-challenged Caco-2 cells, knockdown of the PC biosynthetic enzyme CCTα limited PC preservation by 2-OHOA, while PC(34:1) supplementation attenuated barrier dysfunction, supporting a functional contribution for PC homeostasis to epithelial protection. Together, these findings support preventive effects of 2-OHOA in experimental colitis, accompanied by preservation of lipid homeostasis and epithelial barrier function and reduced inflammatory signaling.

Source: Journal of Lipid Research

DOI: 10.1016/j.jlr.2026.101180

Authors: Lin Lin, Jianyu Zhu, Yibin Ren, Xiong Su

Institutions: Soochow University, The Fourth Affiliated Hospital of Soochow University (Suzhou Dushu Lake Hospital)

Language: English

Topic: Fatty Acid Research and Health

Subfield: Nutrition and Dietetics

Field: Nursing

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,430