High-fat diet enhances cell proliferation and compromises intestinal permeability in a translational canine intestinal organoid model.

Publisher: BioMed Central Country of Publication: England NLM ID: 101741148 Publication Model: Electronic Cited Medium: Internet ISSN: 2661-8850 (Electronic) Linking ISSN: 26618850 NLM ISO Abbreviation: BMC Mol Cell Biol Subsets: MEDLINE

Original Publication: [London] : BioMed Central, [2019]-

Cell Proliferation* ; Diet, High-Fat*/adverse effects ; Intestinal Mucosa*/metabolism ; Intestinal Mucosa*/cytology ; Organoids*/metabolism ; Organoids*/cytology ; Palmitic Acid*/metabolism ; Palmitic Acid*/pharmacology; Animals ; Dogs ; Intestinal Barrier Function ; Intestines/cytology ; Intestines/physiology

Background: Emerging evidence underscores the responsiveness of the mammalian intestine to dietary cues, notably through the involvement of LGR5 + intestinal stem cells in orchestrating responses to diet-driven signals. However, the effects of high-fat diet (HFD) on these cellular dynamics and their impact on gut integrity remain insufficiently understood. Our study aims to assess the multifaceted interactions between palmitic acid (PA), cell proliferation, and the intestinal epithelial barrier using a canine colonoid model. Canine models, due to their relevance in simulating human intestinal diseases, offer a unique platform to explore the molecular mechanisms underlying HFD derived intestinal dysfunction.
Results: Canine colonoids were subjected to PA exposure, a surrogate for the effects of HFD. This intervention revealed a remarkable augmentation of cell proliferative activity. Furthermore, we observed a parallel reduction in transepithelial electrical resistance (TEER), indicating altered epithelium barrier integrity. While E-cadherin exhibited consistency, ZO-1 displayed a noteworthy reduction in fluorescence intensity within the PA-exposed group.
Conclusions: By employing canine intestinal organoid systems, we provide compelling insights into the impact of PA on intestinal physiology. These findings underscore the importance of considering both cell proliferative activity and epithelial integrity in comprehending the repercussions of HFDs on intestinal health. Our study contributes to a deeper understanding of the consequences of HFD on intestinal homeostasis, utilizing valuable translational in vitro models derived from dogs.
(© 2024. The Author(s).)

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K01 OD030515 United States OD NIH HHS; R21 OD031903 United States OD NIH HHS; K01OD030515 United States NH NIH HHS

Keywords: Canine; High-fat diet; Intestinal organoids; Palmitic acid

2V16EO95H1 (Palmitic Acid)

Date Created: 20240430 Date Completed: 20240430 Latest Revision: 20240718

20240719

PMC11059635

10.1186/s12860-024-00512-w

38689222