PET imaging of FATPs
Fatty acid transport proteins (FATPs), also known as solute carrier protein family 27 (SLC27) include six proteins which facilitate the transport of long-chain fatty acids (LCFAs) across plasma and intracellular membranes. Vascular endothelial growth factor B (VEGF-B) regulates the expression of FATPs in the endothelial cells. Other LCFA transporters include FABPpm, fatty acid translocase/CD36, and possibly caveolins.
The six FATPs are found in different tissues:
- FATP1 (SLC27A1, ACSVL5): brown and white adipose tissue, heart and skeletal muscle, brain, kidneys, lungs, keratinocytes in the skin, endothelial cells
- FATP2 (SLC27A2, ACSVL1, VLCS, VLACS, FACVL1): liver, kidney cortex, intestine
- FATP3 (SLC27A3, ACSVL3, VLCS-3): liver, lungs, testis, ovary, epidermal keratinocytes, adrenal gland, endothelial cells
- FATP4 (SLC27A4, ACSVL4): small intestine, liver, kidneys, brain, heart and skeletal muscle, lungs, skin, endothelial cells, white adipose tissue
- FATP5 (SLC27A5, ACSVL6, VLCS-H2, VLACSR, FACVL3, BAL, ACSB, BACS): basal membrane of hepatocytes in the liver
- FATP6 (SLC27A6, ACSVL2, VLCS-H1, FACVL2): heart and skeletal muscle, testis, adrenal glands, kidneys, bladder, uterus, skin
At least FATP1 can translocate from the cytoplasm to the plasma membrane in response to insulin. FATP1 is also found in mitochondria.
FATP2 can function also as acyl-CoA synthetase (ACS), activating long and very long chain FAs.
Fatty acid translocase/CD36 (FAT/CD36) is found in the heart and skeletal muscle, intestine, adipose tissue, spleen, platelets, monocytes and macrophages, endothelium, epidermis, kidneys, brain, and liver. It has an important role in regulation of FA oxidation and esterification, but it also has numerous other functions. In leukocytes it even works as a selective sensor of microbial diacylglycerides.
Insulin and muscle contractions can increase cellular LCFA uptake by inducing the translocation of FAT/CD36 to the plasma membrane.
The effect of FAT/CD36 deficiency on FA uptake in humans has been studied with [11C]palmitate PET (Hames et al., 2014).
Caveolae are specialized flask-shaped microdomains of the plasma membrane, which get their shape from caveolin proteins. They contain signalling and receptor proteins, and fatty acid translocase/CD36. Caveolin-1 and caveolin-2 are found in almost all tissues except in the heart and skeletal muscle, which contain caveolin-3. The role of caveolins in FA transport is yet controversial.
Anderson CM, Stahl A. SLC27 fatty acid transport proteins. Mol Aspects Med. 2013; 34(2-3): 516-528.
Eelen G, de Zeeuw P, Simons M, Carmeliet P. Endothelial cell metabolism in normal and diseased vasculature. Circ Res. 2015; 116(7): 1231-1244.
Glatz JFC, Luiken JJFP, Bonen A. Membrane fatty acid transporters as regulators of lipid metabolism: implications for metabolic disease. Physiol Rev. 2010; 90: 367-417.
Hagberg C, Mehlem A, Falkevall A, Muhl L, Eriksson U. Endothelial fatty acid transport: role of vascular endothelial growth factor B. Physiology (Bethesda) 2013; 28(2): 125-134.
Hames KC, Vella A, Kemp BJ, Jensen MD. Free fatty acid uptake in humans with CD36 deficiency. Diabetes 2014; 63(11): 3606-3614.
Kazantzis M, Stahl A. Fatty acid transport proteins, implications in physiology and disease. Biochim Biophys Acta 2012; 1821(5): 852-857.
Kivelä R, Bry M, Robciuc MR, Räsänen M, Taavitsainen M, Silvola JM, Saraste A, Hulmi JJ, Anisimov A, Mäyränpää MI, Lindeman JH, Eklund L, Hellberg S, Hlushchuk R, Zhuang ZW, Simons M, Djonov V, Knuuti J, Mervaala E, Alitalo K. VEGF-B-induced vascular growth leads to metabolic reprogramming and ischemia resistance in the heart. EMBO Mol Med. 2014; 6(3): 307-321.
Putri M, Syamsunarno MR, Iso T, Yamaguchi A, Hanaoka H, Sunaga H, Koitabashi N, Matsui H, Yamazaki C, Kameo S, Tsushima Y, Yokoyama T, Koyama H, Abumrad NA, Kurabayashi M. CD36 is indispensable for thermogenesis under conditions of fasting and cold stress. Biochem Biophys Res Commun. 2015; 457(4): 520-525.
Created at: 2015-10-13
Updated at: 2017-10-07
Written by: Vesa Oikonen