ArticleCellular and molecular gastroenterology and hepatology2026
High-Fat Diet Remodels Plasma Membrane Rigidity to Potentiate Colonocyte Stemness in Mice.
Article in Cellular and molecular gastroenterology and hepatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
BACKGROUND &
aimsObesity and consumption of a high-fat diet are established risk factors for colorectal cancer. However, the cellular mechanisms linking dietary lipid exposure to intestinal stem cell dysregulation remain incompletely defined. We therefore investigated whether a high-fat diet perturbs plasma membrane homeostasis to potentiate colonocyte stemness in mice.
methodsMice were placed on a chronic 12-week high-fat diet or control (low-fat diet) feeding regimen, or a short-term 1-week high-fat diet exposure. In addition, genetically obese leptin receptor-deficient (db/db) vs (db/+) wild-type mice were examined. Membrane free cholesterol and rigidity were quantified in colonic crypts and leucine-rich repeat-containing G-protein coupled receptor 5
resultsChronic high-fat diet feeding in mice increased membrane free cholesterol content and rigidity in colonic stem cells and enhanced epidermal growth factor receptor and low-density lipoprotein receptor-related protein 6 receptor nanoclustering. This alteration in plasma membrane homeostasis resulted in the overactivation of β-catenin and expansion of the intestinal stem cell niche (eg, stem cell proliferation and organoid-forming efficiency). Notably, genetically induced obesity in db/db mice did not recapitulate the high-fat diet membrane phenotype, highlighting a diet-specific effect.
conclusionsCollectively, these findings identify plasma membrane remodeling as a previously unrecognized mechanism linking dietary lipids to aberrant intestinal stem cell homeostasis and colorectal cancer risk.
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