What question did this study set out to answer?

This research aims to elucidate the role of FABP5 in mesenteric lymphatic dysfunction associated with creeping fat in Crohn's disease.

January 23, 2026

P0110Mesenteric lymphatic dysfunction in Creeping Fat is ameliorated via FABP5 inducing Fatty Acid metabolic Reprogramming to Alleviate Enteritis in Crohn’s disease

Key Points

This research aims to elucidate the role of FABP5 in mesenteric lymphatic dysfunction associated with creeping fat in Crohn's disease.
Visualized mesenteric lymphatic vessel morphology using light-sheet imaging.
Analyzed FABP5 expression in lymphatic endothelial cells from postoperative recurrence cohorts.
Validated the effect of FABP5 in a chronic colitis model with specific knockout mice.
Conducted co-culture studies with CrF-conditioned medium and assessed various cell functions.
Performed lipidomics to analyze fatty acid profiles in CrF-conditioned medium.
Mesenteric lymphatic vessels in creeping fat showed dilation and straightening.
Lower FABP5 levels correlated with higher CD recurrence risk.
FABP5 activation improved lymphatic endothelial cell function and fatty acid oxidation.
ALA administration alleviated colitis and restored lymphatic drainage in wild-type mice.
FABP5 knockout significantly reduced these beneficial effects.

Abstract

Abstract Background Creeping fat (CrF), a hallmark manifestation of Crohn’s disease (CD), is linked to inflammatory intestinal stricture and perhaps postoperative recurrence. Mesenteric lymphatic vessel (MLV) dysfunction is closely associated with CrF formation, however, the mechanism underlying MLV involvement remains unelucidated. Methods We firstly visualized MLV morphology in the CrF using the Adipo-Clear method with modifications for light-sheet imaging. The clinical significance of fatty acid binding protein 5 (FABP5) expression in CrF-lymphatic endothelial cells (CrF-LECs) was analyzed in postoperative recurrence cohort. The effect of FABP5 on MLVs function was validated in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced chronic colitis model on LEC-specific FABP5 knockout (Fabp5ΔLEC) mice. Small intefering FABP5-transfected LECs were co-cultured with CrF-conditioned medium (CrF-CM), followed by analyses of cell functions (proliferation, migration, tube formation, and permeability), transcriptomics, untargeted metabolomics, and biomolecular experiments. Lipidomics analyzed free fatty acids in CrF-CM. Alfar-Linolenic acid (ALA) was intragastrically administered to TNBS-induced Fabp5ΔLEC mice to evaluate its effects in vivo. Results MLVs in CrF exhibited dilation and straightening. Lower CrF-LVD and reduced LEC-FABP5 expression correlated with higher CD recurrence risk. More severe colitis and impaired lymphatic drainage were exhibited in TNBS-induced Fabp5ΔLEC mice. In CrF-LECs, highly expressed FABP5 activated PPARγ, which promoted CPT1A transcription, regulated fatty acid oxidation (FAO), and ultimately improved LEC function. CrF released multiple long-chain FAs, among which α-linolenic acid (ALA) regulated FABP5 expression and FAO rate in CrF-LECs. ALA alleviated TNBS-induced colitis and restored lymphatic drainage in wild-type mice, but these effects were significantly attenuated in Fabp5ΔLEC mice. Conclusion FABP5 reprograms fatty acid metabolism via FABP5/PPARγ/CPT1A in CrF-LEC, improving lymphatic function to relieve CD inflammation, offering a new target for CD lymphatic-targeted therapy. Conflict of interest: Mr. Yongheng, Wang: No conflict of interest Da, Zhang: No conflict of interest Weijie, Chen: No conflict of interest Xiaolei, Wang: No conflict of interest

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Cite This Study

Yongheng et al. (Thu,) studied this question.

synapsesocial.com/papers/69730ed4c8125b09b0d1ea43 https://doi.org/https://doi.org/10.1093/ecco-jcc/jjaf231.291

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