FABPs and PET

Fatty acid binding proteins (FABPs) are small (14-15 kDa) cytosolic proteins that bind unesterified long-chain fatty acids (LCFAs), eicosanoids, endocannabinoids, and some other hydrophobic ligands, even with nanomolar affinity. FABPs facilitate fatty acid (FA) transport, metabolism, and storage, interact with membrane proteins and intracellular proteins, and regulate tissue- and cell-specific lipid responses. FABPs play a role in inflammatory responses.

Humans have at least 9 FABP isoforms:

Liver contains FABP1, which transports LCFAs to mitochondria for β-oxidation, and interacts with PPARα nuclear receptors.

Intestine contains FABP1 and FABP2, and the distal small intestine contains also FABP6. FABP1 participates in transport of LCFAs into β-oxidation, incorporation of monoglycerides into phospholipids, and production of chylomicrons. FABP2 directs LCFAs into triglyceride synthesis. FABP6 transports bile acids.

Cardiac and skeletal muscle contains FABP3, which transports LCFAs to β-oxidation and phospholipid and triglyceride synthesis, and interacts with nuclear receptors. Endothelial cells in these tissues contain FABP4 and FABP5, of which at least FABP4 is regulated by VEGF. In addition to FABPs, myoglobin binds fatty acids, which may have role in regulation of FA and oxygen metabolism in cardiomyocytes and type 1 myocytes.

Adipose tissue has very high levels of FABP4, and very low levels of FABP5. FABPs play a role in triglyceride (TG) storage, regulation of FA concentrations, production of inflammatory cytokines, and interact with PPAR nuclear receptors.

Macrophages contain FABP4 and FABP5, functioning in cytokine production, and interacting with PPARγ nuclear receptors and JAK2 signalling pathway.

Central nervous system contains FABP3, FABP5, and FABP7. FABP3 supplies arachidonic acid for production of phospholipids, and maintains balance between certain polyunsaturated FAs. FABP5 supplies LCFAs for production of membranes, participates in retinoic acid utilization, and interacts with nuclear receptors. FABP7 provides neurons with docosahexaenoic acid for membrane synthesis and signalling. In peripheral nervous system, FABP8 (not found in the brain) participates in production of lipids for the myelin membranes.

In addition to its intracellular functions, FABP4 is also an adipokine, secreted from adipocytes and macrophages. FABP4 is therefore assumed to mediate the inflammatory responses linked to lipid metabolism, and have a role in metabolic syndrome and atherosclerosis. Vascular inflammation, measured using [18F]FDG PET, is independently associated with FABP4 concentration in plasma (Yoo et al., 2011).

Effects of FABPs on FA uptake have been studied with labelled fatty acid ligands, such as [125I]BMIPP, in mice strains which do not express certain FABP subtypes.

FABP3 is expressed in gliomas in grade-dependent manner. FABP3-binding peptide, CooP, has been developed and labelled for SPECT imaging (Hyvönen et al., 2014), and derivative peptides with higher affinity have been developed (Ayo et al., 2020).

A PET radioligand for FABP4, [18F]FTAP1 has been developed and validated in mouse tumour model (Temma et al., 2015).

FABPpm

Plasma membrane fatty acid binding protein (FABPpm) is a protein located at plasma membrane in several tissues, at least in the liver, heart and skeletal muscle, adipose tissue, and intestine. It is also located in the mitochondria where it has the name mitochondrial aspartate aminotransferase (mAspAt). It transports long-chain fatty acids across the plasma membrane, together with fatty acid transport proteins and fatty acid translocase/CD36.


See also:


Literature

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Updated at: 2023-01-30
Created at: 2015-10-13
Written by: Vesa Oikonen