Fatty acid-binding protein

About: Fatty acid-binding protein is a research topic. Over the lifetime, 1721 publications have been published within this topic receiving 81530 citations. The topic is also known as: FABP.

Lipid Metabolism and Peroxisome Proliferator-Activated Receptor Signaling Pathways Participate in Late-Phase Liver Regeneration

Abstract: Liver regeneration (LR) is of great clinical significance in various liver-associated diseases. LR proceeds along a sequence of three distinct phases: priming/initiation, proliferation, and termination. Compared with the recognition of the first two phases, little is known about LR termination and structure/function reorganization. A combination of "omics" techniques, along with bioinformatics, may provide new insights into the molecular mechanism of the late-phase LR. Gene, protein, and metabolite profiles of the rat liver were determined by cDNA microarray, two-dimensional electrophoresis, and HPLC-MS analysis. Pathway enrichment analysis was performed to identify the pathways: 427 differentially expressed genes extracted from the microarray experiment revealed two expression patterns representing the early and late phase of LR. Functionally, the genes expressing at a higher level at the early phase than at the late phase were mainly involved in the response to stress, proliferation, and resistance to apoptosis, while those expressing at a lower level at the early phase than at the late phase were mainly engaged in lipid metabolism. Compared with the sham-operation control (SH) group, 5 proteins in the 70% partial hepatectomy (70%PHx) group were upregulated at the protein level, and 3 proteins were downregulated at 168 h after the 70%PHx. E-FABP, an upregulated fatty acid binding protein, was found to be involved in the peroxisome proliferator-activated receptor (PPAR) signaling pathway. The metabolomic data confirmed the enhancement of lipid metabolism by the detection of the intermediate and final metabolites. We've concluded that increased lipid metabolism and activated PPAR signaling pathways play important roles in late-phase LR.

Solution structure of human intestinal fatty acid binding protein with a naturally-occurring single amino acid substitution (A54T) that is associated with altered lipid metabolism.

Abstract: The human intestinal fatty acid binding protein (I-FABP) belongs to a family of intracellular lipid binding proteins. This 15 kDa protein binds dietary long-chain fatty acids in the cytosol of enterocytes. A naturally-occurring nucleotide polymorphism at codon 54, which produces either an alanine-containing (A54) or a threonine-containing (T54) protein, has been identified. These two I-FABP forms display differential binding and transport of fatty acids across cells, and their alleles are associated with in vivo insulin resistance and/or altered lipid metabolism in several human populations. The three-dimensional solution structure of the more common A54 form was previously determined in our lab. A direct comparison between human A54 and T54 I-FABP has now been performed to help elucidate the structural origins of their physiological distinctions. The solution structure of T54 I-FABP is highly homologous to that of A54 I-FABP, with the same overall three-dimensional fold that includes an antiparallel beta-clam motif. Chemical shift differences between the two proteins suggest only minor local structural changes within the "portal region" and no significant alterations elsewhere. Hence, the slightly stronger binding of fatty acids to T54 I-FABP does not originate from residues in direct contact with the bound fatty acid. Instead, it appears that the larger Thr(54) side chain affects the passage of the ligand through the entry portal. Structural details of this portal region will be discussed in view of the influence residue 54 exerts on the functional properties of human I-FABP.

Partitioning of adipose lipid metabolism by altered expression and function of PPAR isoforms after bariatric surgery.

Abstract: Bariatric surgery remains the most effective treatment for reducing adiposity and eliminating type 2 diabetes; however, the mechanism(s) responsible have remained elusive. Peroxisome proliferator-activated receptors (PPAR) encompass a family of nuclear hormone receptors that upon activation exert control of lipid metabolism, glucose regulation and inflammation. Their role in adipose tissue following bariatric surgery remains undefined. Subcutaneous adipose tissue biopsies and serum were obtained and evaluated from time of surgery and on postoperative day 7 in patients randomized to Roux-en-Y gastric bypass (n=13) or matched caloric restriction (n=14), as well as patients undergoing vertical sleeve gastrectomy (n=33). Fat samples were evaluated for changes in gene expression, protein levels, β-oxidation, lipolysis and cysteine oxidation. Within 7 days, bariatric surgery acutely drives a change in the activity and expression of PPARγ and PPARδ in subcutaneous adipose tissue thereby attenuating lipid storage, increasing lipolysis and potentiating lipid oxidation. This unique metabolic alteration leads to changes in downstream PPARγ/δ targets including decreased expression of fatty acid binding protein (FABP) 4 and stearoyl-CoA desaturase-1 (SCD1) with increased expression of carnitine palmitoyl transferase 1 (CPT1) and uncoupling protein 2 (UCP2). Increased expression of UCP2 not only facilitated fatty acid oxidation (increased 15-fold following surgery) but also regulated the subcutaneous adipose tissue redoxome by attenuating protein cysteine oxidation and reducing oxidative stress. The expression of UCP1, a mitochondrial protein responsible for the regulation of fatty acid oxidation and thermogenesis in beige and brown fat, was unaltered following surgery. These results suggest that bariatric surgery initiates a novel metabolic shift in subcutaneous adipose tissue to oxidize fatty acids independently from the beiging process through regulation of PPAR isoforms. Further studies are required to understand the contribution of this shift in expression of PPAR isoforms to weight loss following bariatric surgery.

The main fatty acid-binding protein in the liver of the shark (Halaetunus bivius) belongs to the liver basic type. Isolation, amino acid sequence determination and characterization.

Abstract: Three fatty acid-binding proteins (FABPs) from the liver of the shark Halaetunus bivius were isolated and characterized: one of them belongs to the liver-type FABP family and the other two to the heart-type FABP family. The complete primary structure of the first FABP, and partial primary structures of the two others, were determined. The liver-type FABP constitutes 69% of the total FABPs, and its amino acid sequence presents the highest identity with chicken, catfish, iguana and elephant fish liver basic FABPs. The L-FABP protein has low affinity for palmitic and oleic acids and high affinity for linoleic and arachidonic acids and other hydrophobic ligands, all of them important for the metabolic functions of the liver. In contrast, both heart-type FABPs have the highest affinity for palmitic acid, the principal fatty acid mobilized from fat deposits for beta-oxidation.