CD36-Mediated Lipid Metabolism and Inflammation

CD36 is a multifunctional class B scavenger receptor expressed on the surface of endothelial cells, adipocytes, myocytes and immune cells. It facilitates the uptake of long-chain fatty acids and various modified lipoproteins, while also acting as a pattern recognition receptor that binds danger- or pathogen-associated molecular patterns. By integrating lipid transport with intracellular signalling, CD36 modulates ceramide formation, vesicular trafficking and inflammatory cascades. Its roles in endothelial fatty acid transfer, macrophage foam-cell formation and insulin signalling underscore a central position at the interface of metabolic homeostasis and innate immunity. Dysregulation of CD36 activity has been implicated in atherosclerosis, insulin resistance, coronary artery disease and infectious inflammation, making it a compelling target for therapeutic intervention in cardiometabolic and immune-mediated disorders.

Research from Nature Portfolio

Endothelial CD36 has been shown to orchestrate a novel pathway of fatty acid trafficking via ceramide-rich caveolae. Binding of fatty acids to apical CD36 triggers Src-dependent phosphorylation of caveolin-1, local ceramide synthesis and budding of small (80–100 nm) exosome-like vesicles containing fatty acids, CD36 and ceramide. These vesicles are secreted basolaterally and deliver fatty acids to underlying muscle cells, as visualised in transwell assays and intravital imaging of skeletal muscle. Genetic or pharmacological ablation of CD36 or key components of this pathway reduces vesicle formation, impairs muscle fatty acid uptake, elevates circulating lipids and alters systemic glucose levels. This work elucidates how endothelial CD36-mediated ceramide dynamics and vesicular transport underpin intercellular lipid exchange and maintain metabolic balance.

CD36-Mediated Lipid Metabolism and Inflammation publication trend

The graph below shows the total number of articles in cd36-mediated lipid metabolism and inflammation across all publications each year (not limited to Nature Index journals).

Technical terms

CD36: A class B scavenger receptor that binds long-chain fatty acids, modified lipoproteins and danger or pathogen patterns, integrating lipid uptake with signalling.

Exosome-like extracellular vesicles (sEVs): Small (50–150 nm) membrane-bound vesicles released by cells, involved in intercellular transfer of lipids, proteins and nucleic acids.

Ceramide: A sphingolipid metabolite generated in the plasma membrane that participates in membrane curvature, vesicle formation and inflammatory signalling.

Hyperinsulinaemic–euglycaemic clamp: A gold-standard procedure to assess insulin sensitivity, in which insulin is infused and blood glucose is maintained at a target level by glucose infusion.

Microvascular perfusion: The flow of blood through the smallest vessels (capillaries and arterioles) critical for tissue oxygenation and nutrient delivery.

MicroRNA (miRNA): Short non-coding RNA molecules that regulate gene expression post-transcriptionally by binding to target mRNAs.

References

1. Endothelial cell CD36 regulates membrane ceramide formation, exosome fatty acid transfer and circulating fatty acid levels. Nature Communications (2023).
2. Microvascular insulin resistance with enhanced muscle glucose disposal in CD36 deficiency. Diabetologia (2024).
3. Small Extracellular Vesicles in the Pericardium Modulate Macrophage Immunophenotype in Coronary Artery Disease. JACC Basic to Translational Science (2024).
4. The function of CD36 in Mycobacterium tuberculosis infection. Frontiers in Immunology (2024).
5. Class B Scavenger Receptor CD36 as a Potential Therapeutic Target in Inflammation Induced by Danger-Associated Molecular Patterns. Cells (2024).