DHHC5 regulates lacteal function and intestinal lipid absorption by maintaining VEGFR2 localization in lipid rafts.

ABSTRACT: The intestinal lymphatic system is essential for lipid absorption, yet its regulatory mechanisms remain poorly understood. Here, we identify DHHC5, an Asp-His-His-Cys (DHHC) motif-containing palmitoyl acyltransferase, as a critical regulator of intestinal lymphatic integrity and lipid uptake. Whole-body inducible Dhhc5 knockout (Dhhc5-IKO) mice were resistant to diet-induced obesity and exhibited impaired intestinal lipid absorption due to lymphatic dysfunction. Similar defects were observed upon specific knockout of DHHC5 in lymphatic endothelial cells (LECs), underscoring its cell-autonomous role. Mechanistically, DHHC5 facilitates vascular endothelial growth factor receptor 2 (VEGFR2) signaling by promoting its lipid raft localization in LECs. We further identified

SUBMITTER: Zhao YY 

PROVIDER: S-EPMC12207882 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature