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From Proteopedia

Fatty Acid Binding Protein

Intracellular lipid chaperones known as fatty acid-binding proteins (FABPs) are a group of molecules that coordinate lipid responses in cells and are also strongly linked to metabolic and inflammatory pathways. FABPs are abundantly expressed 14–15 kDa proteins that reversibly bind hydrophobic ligands, such as saturated and unsaturated long-chain fatty acids, eicosanoids and other lipids, with high affinity.

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Function

Fatty Acids Binding Proteins maintain intracellular lipid homeostasis and also affect systemic lipid metabolism. They have very unique features that allow them to transport and metabolize long chain fatty acids. Studies have suggested that subtle three dimensional changes that occur upon ligand binding may promote specific FABP-protein or FABP-membrane interactions that ultimately determine the particular function of the FABP.

FABPs play a role in the transport of lipids to specific compartments in the cell:

- to lipid droplets for storage;

- to the endoplasmic reticulum for signalling, trafficking and membrane synthesis;

- to the mitochondria or peroxisome for oxidation;

- to cytosolic or other enzymes to regulate their activity;

- to the nucleus for the control of lipid-mediated transcriptional programs via nuclear hormone receptors (NHRs) or other transcription factors that respond to lipids;

- or even outside the cell to signal in an autocrine or paracrine manner.

Disease

- Abundant amount of FABP4 is linked to cardiovascular disease.

- FABP is elevated in patients with celiac disease.

- FABP7 is known to be correlated with cell renal carcinoma. The fatty acid binding protein is upregulated in brain tissue. Overexpression of FABP7 in RCC cells increases cell growth and promotes extracellular signal regulated kinases and activator of transcription 3 signaling.

- Epidermal Fatty Acid binding protein is associated with Sjögren syndrome, a chronic inflammatory autoimmune disease of the salivary glands.

- The urinary level of liver-type fatty acid binding protein (L-FABP)is associated with chronic kidney disease (CKD) and acute kidney injury.

- There is a correlation between fatty acid-binding proteins and atherosclerosis. Increased levels of serum fatty acid-binding protein 4 (FABP4) promote type 2 diabetes (T2DM) and acute ischemic stroke. Fatty acid-binding proteins (FABPs) are cytosolic fatty acid chaperones. Adipocyte fatty acid-binding protein are part of the lipid chaperone fatty acid-binding protein family, is produced in adipocytes and macrophages; gene expression is higher in adipocytes. Circulating AFABP levels are associated with the metabolic syndrome and obesity, type 2 diabetes, insulin resistance, atherogenic dyslipidemia, and fatty liver disease. Increased levels of FABP4 promotes endoplasmic reticulum stress in macrophages and upregulates pro-inflammatory cytokine production.

Relevance

FABPs control metabolic signaling pathways and participate in multiple enzymatic activities. 

- Structure: 14-15 kDa protein molecules, bind strongly and reversibly to hydrophobic ligands.

- Have conformational switches which create folding and promote function thereby deciding the functional conformation.

- Expressed IFABP prevents mitochondria from being morphologically impaired and apoptosis created by Fatty acid ligands.

Structural highlights

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Reference

Ringom, Rune; Axen, Eva; Uppenberg, Jonas; Lundbäck, Thomas; Rondahl, Lena; Barf, Tjeerd. (2004), Substituted benzylamino-6-(trifluoromethyl)pyrimidin-4(1H)-ones: a novel class of selective human A-FABP inhibitors. Elsevier BV., 14:4449-4452. https://doi.org/10.1016/j.bmcl.2004.06.058

Storch, Judith, and Lindsay McDermott. “Structural and functional analysis of fatty acid-binding proteins.” Journal of lipid research vol. 50 Suppl,Suppl (2009): S126-31. doi:10.1194/jlr.R800084-JLR200

Elie AGIM, Bloksgaard M, Sun WY, et al. Local enrichment of fatty acid-binding protein 4 in the pericardial cavity of cardiovascular disease patients. Plos One. 2018;13(11):e0206802. doi:10.1371/journal.pone.0206802.

Oldenburger IB, Wolters VM, Kardol-Hoefnagel T, Houwen RHJ, Otten HG. Serum intestinal fatty acid-binding protein in the noninvasive diagnosis of celiac disease. APMIS: Acta Pathologica, Microbiologica, Et Immunologica Scandinavica. 2018;126(3):186-190. doi:10.1111/apm.12800.

Nagao K, Shinohara N, Smit F, et al. Fatty acid binding protein 7 may be a marker and therapeutic targets in clear cell renal cell carcinoma. BMC Cancer. 2018;18(1):1114. doi:10.1186/s12885-018-5060-8.

Shinzawa M, Dogru M, Den S, et al. Epidermal Fatty Acid-Binding Protein: A Novel Marker in the Diagnosis of Dry Eye Disease in Sjögren Syndrome. International Journal Of Molecular Sciences. 2018;19(11). doi:10.3390/ijms19113463.

Watanabe S, Ichikawa D, Sugaya T, et al. Urinary Level of Liver-Type Fatty Acid Binding Protein Reflects the Degree of Tubulointerstitial Damage in Polycystic Kidney Disease. Kidney & Blood Pressure Research. 2018;43(6):1716-1729. doi:10.1159/000495389.

Li S, Bi P, Zhao W, et al. Prognostic Utility of Fatty Acid-Binding Protein 4 in Patients with Type 2 Diabetes and Acute Ischemic Stroke. Neurotoxicity Research. 2018;(2):309. doi:10.1007/s12640-017-9792-z.

Sarkar-Banerjee S, Chowdhury S, Sanyal D, Mitra T, Roy SS, Chattopadhyay K. The Role of Intestinal Fatty Acid Binding Proteins in Protecting Cells from Fatty Acid Induced Impairment of Mitochondrial Dynamics and Apoptosis. Cellular Physiology And Biochemistry: International Journal Of Experimental Cellular Physiology, Biochemistry, And Pharmacology. 2018;51(4):1658-1678. doi:10.1159/000495672.