Faculty, Staff and Student Publications
Publication Date
7-1-2022
Journal
Immunometabolism
Abstract
Dysregulation of lipid deposition into and mobilization from white adipose tissue (WAT) underlies various diseases. Long-chain fatty acids (LCFA) and cholesterol trafficking in and out of adipocytes is a process relying on transporters shuttling lipids from the plasma membrane (PM) to lipid droplets (LD). CD36 is the fatty acid translocase (FAT) that transports LCFA and cholesterol across the PM. Interactions of CD36 with proteins PHB1, ANX2, and CAV1 mediate intercellular lipid transport between adipocytes, hematopoietic, epithelial, and endothelial cells. Intracellularly, the FAT complex has been found to regulate LCFA trafficking between the PM and LD. This process is regulated by CD36 glycosylation and S-acylation, as well as by post-translational modifications of PHB1 and ANX2, which determine both protein-protein interactions and the cellular localization of the complex. Changes in extracellular and intracellular LCFA levels have been found to induce the post-translational modifications and the function of the FAT complex in lipid uptake and mobilization. The role of the CD36/PHB1/ANX2 complex may span beyond lipid trafficking. The requirement of PHB1 for mitochondrial oxidative metabolism in brown adipocytes has been revealed. Cancer cells which take advantage of lipids mobilized by adipocytes and oxidized in leukocytes are indirectly affected by the function of FAT complex in other tissues. The direct importance of CD36 interaction with PHB1/and ANX2 in cancer cells remains to be established. This review highlights the multifaceted roles of the FAT complex in systemic lipid trafficking and discuss it as a potential target in metabolic disease and cancer.
Keywords
fatty acid translocase, lipid metabolism
DOI
10.1097/IN9.0000000000000001
PMID
35991116
PMCID
PMC9380421
PubMedCentral® Posted Date
8-15-2022
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Included in
Biochemical Phenomena, Metabolism, and Nutrition Commons, Biomedical Informatics Commons