Palmitoylation-dependent modulation of CD36 trafficking and signaling integrates lipid uptake with metabolic disease pathogenesis

Mingxun Li; Haoran Jia; Lei Zhang; Peng Chen; Shimeng Wang; Yongjiang Mao; Zhangping Yang

doi:10.1016/j.phrs.2025.107935

Pharmacological Research (Oct 2025)

Palmitoylation-dependent modulation of CD36 trafficking and signaling integrates lipid uptake with metabolic disease pathogenesis

Mingxun Li,
Haoran Jia,
Lei Zhang,
Peng Chen,
Shimeng Wang,
Yongjiang Mao,
Zhangping Yang

Affiliations

Mingxun Li: Correspondence to: College of Animal Science and Technology, Yangzhou University, 88 University South Avenue, Yangzhou, Jiangsu 225009, China.; Key Laboratory of Animal Genetics & Breeding and Molecular Design of Jiangsu province, College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu 225009, China
Haoran Jia: Key Laboratory of Animal Genetics & Breeding and Molecular Design of Jiangsu province, College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu 225009, China
Lei Zhang: Key Laboratory of Animal Genetics & Breeding and Molecular Design of Jiangsu province, College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu 225009, China
Peng Chen: Key Laboratory of Animal Genetics & Breeding and Molecular Design of Jiangsu province, College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu 225009, China
Shimeng Wang: Key Laboratory of Animal Genetics & Breeding and Molecular Design of Jiangsu province, College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu 225009, China
Yongjiang Mao: Key Laboratory of Animal Genetics & Breeding and Molecular Design of Jiangsu province, College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu 225009, China
Zhangping Yang: Correspondence to: College of Animal Science and Technology, Yangzhou University, 88 University South Avenue, Yangzhou, Jiangsu 225009, China.; Key Laboratory of Animal Genetics & Breeding and Molecular Design of Jiangsu province, College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu 225009, China

DOI: https://doi.org/10.1016/j.phrs.2025.107935
Journal volume & issue: Vol. 220
p. 107935

Abstract

Read online

CD36 is a multifunctional lipid transporter that facilitates long-chain fatty acid uptake and orchestrates metabolic signaling in energy-demanding tissues. Recent studies have uncovered site-specific palmitoylation as a crucial post-translational modification that governs CD36 subcellular trafficking, stabilizing its localization within lipid rafts and regulating its endocytic recycling between the plasma membrane, endosomes, and lipid droplets. This dynamic palmitoylation–depalmitoylation cycle enables CD36 to spatially and temporally couple lipid transport with signal transduction in response to nutritional and hormonal cues. Disruption of this regulatory axis leads to aberrant fatty acid uptake, inflammatory activation, and metabolic dysfunction, contributing to the pathogenesis of non-alcoholic fatty liver disease (NAFLD), type 2 diabetes mellitus (T2DM), and atherosclerosis. Here, we delineate the mechanistic basis of CD36 palmitoylation-dependent trafficking and its integration with lipid handling, signal transduction, and disease pathogenesis. Targeting this regulatory interface offers a promising avenue for therapeutic intervention in metabolic disorders.

Published in Pharmacological Research

ISSN: 1096-1186 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.sciencedirect.com/journal/pharmacological-research

About the journal

Abstract

Keywords