The Biological Functions and Regulatory Mechanisms of Fatty Acid Binding Protein 5 in Various Diseases

Abstract

In recent years, fatty acid binding protein 5 (FABP5), also known as fatty acid transporter, has been widely researched with the help of modern genetic technology. Emerging evidence suggests its critical role in regulating lipid transport, homeostasis, and metabolism. Its involvement in the pathogenesis of various diseases such as metabolic syndrome, skin diseases, cancer, and neurological diseases is the key to understanding the true nature of the protein. This makes FABP5 be a promising component for numerous clinical applications. This review has summarized the most recent advances in the research of FABP5 in modulating cellular processes, providing an in-depth analysis of the protein's biological properties, biological functions, and mechanisms involved in various diseases. In addition, we have discussed the possibility of using FABP5 as a new diagnostic biomarker and therapeutic target for human diseases, shedding light on challenges facing future research.

Keywords: FABP5; cell differentiation; immune response; lipid homeostasis; lipid metabolism; tumorigenesis.

FIGURE 1

Putative functions of FABP5 in the cell. As lipid chaperones, FABP5 may actively facilitate lipid transportion to specific intracellular compartments and thereby realize different biological functions, such as the lipid droplet storage, signaling transduction, trafficking and membrane synthesis in endoplasmic reticulum, oxidation in mitochondria or peroxisome, lipid-mediated transcriptional regulation in the nucleus, or even signaling in an autocrine or paracrine manner outside the cell.

FIGURE 2

Amino acid sequences and tertiary structure of the human FABP family members. (A) Amino acid sequences of the human FABPs. Amino acid sequences were obtained from the National Center for Biology Information (NCBI) website (www.ncbi.nlm.nih.gov/). (B) The tertiary structure of the human FABP family members 1–9. The structures were adjusted to a similar angle. The structures were obtained from RCSB PDB (Research Collaboration for Structural Bioinformatics, Protein Data Bank) (https://www.rcsb.org/structure/). FABP1 (PDB code: 1LFO), FABP2 (PDB code: 3IFB), FABP3 (PDB code: 4TKB), FABP4 (PDB code: 3P6D), FABP5 (PDB code: 4AZQ), FABP6 (PDB code: 5L8I), FABP7 (PDB code: 1FDQ), FABP8 (PDB code: 1PMP), FABP9 (PDB code: 4A60).

FIGURE 3

Expression, function and diseases of FABPs. FABPs function pleiotropically in human body to maintain tissue homeostasis in health and to participate in disease pathogenesis.

FIGURE 4

Tertiary structure of human FABP5. (A) The tertiary structure of FABP5 consists of 2 α-helices and 10 anti-parallel β-strands. (B) The disulphide bridge between cysteines 120 and 127 in FABP5 promotes protein stability.

FIGURE 5

The role and mechanism of FABP5 in lipid metabolism, homeostasis, cell proliferation and differentiation. The roles and corresponding signal pathways of FABP5 in metabolic syndrome, adipogenesis, lipid homeostasis, proliferation, differentiation, metastasis, airway remodeling and inflammation, apoptosis and autophagic responses. FAs, fatty acids; VEGF, vascular endothelial growth factor.

FIGURE 6

The role and mechanism of FABP5 in immune response and inflammatory process. The bio-function and corresponding mechanisms of FABP5 in antigen-presenting, recruitment of tumoricidal effector cells, cytoplasmic immune response, Th17-cell differentiation, and mitochondrial integrity in Tregs. PUFA, polyunsaturated fatty acids.

FIGURE 7

The role and mechanism of FABP5 in tumorigenesis and cancer development. FABP5 plays critical roles in cancer initiation and progression through the AKT pathway, NF-κB pathway, IL pathway, EGFR pathway, p53 pathway, and so on. AA: arachidonic acid; AEA: endocannabinoid anandamide; CRABP: cytosolic retinoic acid-binding protein; DPPC: dipalmitoyl phosphatidyl choline; EGFR: epidermal growth factor receptors; ERK: extracellular regulated protein kinases. FAAH: fatty acid amide hydrolase; FAS: fatty acids; FFA: free fatty acids; FABP5: fatty acid binding protein 5; GIP: glucose-dependent insulinotropic polypeptide; IFN: interferon; IL: interleukin; LCFAS: long-chain fatty acids; MMP: matrix metalloproteinase; NF-κB: nuclear factor-kappa B; NGF: nerve growth factor; PI3K: phophatidylinositol-3-kinase; PPAR: peroxisome proliferator-activated receptor; PPRE: proliferator-activated response element; RAR: retinoic acid receptor; ROS: reactive oxygen species; STAT: signal transducer and activator of transcription; Tc: cytotoxic T cell, CD8⁺ T cell; Th: helper T cell, CD4⁺ T cell; Treg: regulatory T cell; Tm: memory T cell.