Disease relevance of FABP1

• How these signaling molecules reach the nuclear receptor is not known; however, similarities in ligand specificity suggest the liver fatty acid binding protein (L-FABP) as a possible candidate [1].
• Furthermore, cobalt, a chemical agent known to mimic hypoxia, inhibits trophoblast cells differentiation and diminishes H-, L-FABP and PPARs expression [2].
• OBJECTIVE: Liver-type fatty acid-binding protein (l-FABP) is expressed in renal proximal tubules and is reported to be a useful marker for progression of chronic glomerulonephritis [3].
• Elevated plasma levels of both I-FABP and L-FABP were found in patients suffering from intestinal diseases, while only L-FABP was increased in cases of purely hepatocellular injury [4].
• Even though linoleate and CLA were incorporated into lipids of hepatoma cells to the same extent, linoleate had little or no effect on ACO, CYP4A1, or L-FABP mRNA [5].

High impact information on FABP1

• The intestine is lined by a continuously regenerating epithelium that maintains gradients in 'liver' fatty acid binding protein (L-FABP) gene expression along its horizontal and vertical axes, i.e., from duodenum to colon and from crypt to villus tip [6].
• Nucleotides -596 to +21 of the rat L-FABP gene correctly directed hGH expression to enterocytes and hepatocytes [6].
• To identify cis-acting DNA sequences responsible for these regional differences, we linked portions of the L-FABP gene's 5' nontranscribed region to the human growth hormone (hGH) gene and examined hGH expression in transgenic mice [6].
• The "liver" fatty acid binding protein (L-FABP) gene represents a useful model for analyzing the molecular basis for intestinal epithelial differentiation since it exhibits cell-specific, region-specific, as well as developmental stage specific expression [7].
• In addition, L-FABP/hGH fusion genes were used to identify subsets of enteroendocrine cells based on their ability to support hGH synthesis in several different pedigrees of transgenic mice [7].

Chemical compound and disease context of FABP1

• The aim of this study was to verify whether genetic variations in the LFABP gene may impact on plasma lipoprotein/lipid levels in the fasting state as well as on the response to a lipid-lowering therapy with fenofibrate on plasma lipids and obesity variables [8].
• The presence of cysteine and methionine groups together with an ability to bind long-chain fatty acid (LCFA) oxidation products makes liver fatty acid binding protein (L-FABP) an attractive candidate against hepatocellular oxidative stress [9].
• RESULTS: In 150 healthy subjects, urinary L-FABP averaged 3.6 +/- 0.2 microg/g creatinine, whereas the values were significantly increased in patients with hypertension (5.2 +/- 0.4, P = 0.010), diabetes mellitus (5.5 +/- 0.5, P < 0.001), and chronic hepatitis (5.8 +/- 1.0, P = 0.022) [10].
• 16 h after administration, LPS (100 microg/100 g body weight) produced a 72% decrease in L-FABP mRNA levels in liver and this effect was sustained for 24 h [11].
• The effects of non-esterified fatty acids (NEFA) and hormone dehydroepiandrosterone (DHEA) on the levels of mRNAs of protein kinase C (PKC) -delta and -epsilon isoforms and those of liver fatty acid binding protein (L-FABP) were investigated in the human hepatoma HepG2 cell line [12].

Biological context of FABP1

• Homology of synteny has been further defined between the proximal region of mouse chromosome 6 and with the 2p13-p11 region of human chromosome 2 encompassing TGFA, IGK, CD8A, and FABP1 [13].
• Final and quantitative proof for L-FABP mediation was obtained in transactivation assays upon incubation of transiently and stably transfected HepG2 cells with saturated, monounsaturated, and polyunsaturated fatty acids as well as with hypolipidemic drugs [1].
• Knowledge of the primary amino acid sequence of L-FABP and possible functional domains will be pivotal in further defining and understanding the mechanism of ligand binding and transfer by this protein [14].
• Human liver fatty acid binding protein (L-FABP) cDNA clones were identified in a liver cDNA library [14].
• This finding implies that L-FABP has a significant role in oxidative stress [15].

Anatomical context of FABP1

• In localization studies using laser-scanning microscopy, we show that L-FABP and PPARalpha colocalize in the nucleus of mouse primary hepatocytes [1].
• The preference of I-LBP (but not L-FABP) for conjugated bile acids is in accordance with a specific role in bile acid reabsorption in the ileum [16].
• The L-FABP-expressing cell line had a reduced intracellular ROS level versus control [15].
• Liver-type fatty acid binding protein (L-FABP) has been proposed to be involved in the transport of fatty acids and peroxisome proliferators from the cytosol into the nucleus for interaction with the peroxisome proliferator-activated receptors (PPARs) [17].
• L-FABP tissue contents were markedly higher, amounting to 124 and 198 mug/g ww in duodenum and jejunum, and to 58, 26 and 44 mug/g ww in ileum, proximal colon and distal colon, respectively [4].

Associations of FABP1 with chemical compounds

• In vitro binding studies revealed that the bacterially expressed recombinant I-15P showed much lower affinities for palmitate and oleate than L-FABP [18].
• In conclusion, this study showed that there is no correlation between the expression of H- and L-FABP and LA uptake by trophoblast cells and that bezafibrate and LA greatly impaired trophoblast cells differentiation [2].
• Urinary l-FABP levels in groups B-D were significantly higher than those in healthy subjects (group E, 5.8 +/- 4.0 microg/g creatinine) (group B, P < 0.05; group C, P < 0.01; group D, P < 0.01) [3].
• Moreover, treatment of hepatocytes with antisense mRNA directed against ES10 or L-FABP abolished both tamoxifen and MBoPE binding [19].
• Inhibition of P-450 4A1 markedly diminished, via a pre-translational mechanism, the CF induction of L-FABP and peroxisomal beta-oxidation [20].

Physical interactions of FABP1

• Subfamily proteins bind retinoids, subfamily II proteins bind bulky ligands, examples are intestinal bile acid binding protein (I-BABP) and liver fatty acid binding protein (L-FABP) which binds 2 ligand molecules, preferably monounsaturated and n-3 fatty acids [21].
• Finally, both cis-parinaric acid and cis-parinaroyl CoA were much less ordered in the I-FABP ligand binding site than with L-FABP [22].
• Earlier markers such as myoglobin and heart fatty acid binding protein (hFABP) may provide information earlier; however, the true role of such markers remains unclear when applied to real life patient cohorts [23].
• BACKGROUND/AIM: Urinary liver-type fatty-acid-binding protein (L-FABP) is a useful clinical marker in the monitoring of chronic kidney disease (CKD) associated with tubulointerstitial damage [24].

Regulatory relationships of FABP1

• Similarly, hydrocortisone and insulin enhanced the cellular content of I- and L-FABP whereas leptin triggered I-FABP expression only after an 8-hour incubation [25].
• Female rats differ from males, however, in showing a greater hepatic abundance of L-FABP which is expressed almost equally throughout the acinus [26].

Other interactions of FABP1

• The liver only contains liver-type FABP (L-FABP), but co-expression of H-FABP and L-FABP occurs in the kidney [27].
• Accordingly, besides I-FABP, also L-FABP is a useful plasma marker for the detection of intestinal injury, especially in patients undergoing intestinal surgery [4].
• Liver fatty acid binding protein (L-FABP) contains amino acids that are known to possess antioxidant function [15].
• Urinary 8-hydroxydeoxyguanosine and serum free fatty acids (FFAs) were also measured in group B. RESULTS: Urinary l-FABP levels in groups A-D were 6.2 +/- 4.6 microg/g creatinine, 19.6 +/- 13.5 microg/g creatinine, 26.8 +/- 20.4 microg/g creatinine, and 52.4 +/- 46.8 microg/g creatinine, respectively [3].
• Hepatocyte nuclear factor (HNF)-1alpha plays a central role in intestinal and hepatic gene regulation and is required for hepatic expression of the liver fatty acid binding protein gene (Fabpl) [28].

Analytical, diagnostic and therapeutic context of FABP1

• Western blot showed expression of 14-kd L-FABP protein in pcDNA-FABP-transfected cells, but not in vector-transfected cells [15].
• Expression of L-FABP was documented by regular reverse transcription polymerase chain reaction (RT-PCR), real-time RT-PCR, and Western blot [15].
• Urinary l-FABP levels were measured by enzyme-linked immunosorbent assay [3].
• The most pronounced induction is seen after treatment with peroxisome proliferators, which induce L-FABP coordinately with microsomal cytochrome P-450 4A1 and the enzymes of peroxisomal fatty acid beta-oxidation [20].
• DESIGN AND METHODS: I-FABP and L-FABP were measured with specific immunoassays in autopsy samples of the intestine (duodenum, jejunum, ileum and colon) of 23 subjects and in plasma samples from patients (n = 51) with intestinal and/or hepatic disease [4].

References