Intracellular Fatty Acid Binding Proteins Research Articles

Fatty acid binding protein 4 has prognostic value in peripheral artery disease

ObjectivePeripheral artery disease (PAD) remains undertreated, despite its association with major amputation and mortality. This is partly due to a lack of available disease biomarkers. The intracellular protein fatty acid binding protein 4 (FABP4) is implicated in diabetes, obesity, and metabolic syndrome. Given that these risk factors are strong contributors to vascular disease, we assessed the prognostic ability of FABP4 in predicting PAD-related adverse limb events. MethodsThis was a prospective case-control study with 3 years of follow-up. Baseline serum FABP4 concentrations were measured in patients with PAD (n = 569) and without PAD (n = 279). The primary outcome was major adverse limb event (MALE; defined as a composite of vascular intervention or major amputation). The secondary outcome was worsening PAD status (drop in ankle-brachial index ≥0.15). Kaplan-Meier and Cox proportional hazards analyses adjusted for baseline characteristics were conducted to assess the ability of FABP4 to predict MALE and worsening PAD status. ResultsPatients with PAD were older and more likely to have cardiovascular risk factors compared with those without PAD. Over the study period, MALE and worsening PAD status occurred in 162 (19%) and 92 (11%) patients, respectively. Higher FABP4 levels were significantly associated with 3-year MALE (unadjusted hazard ratio [HR], 1.19; 95% confidence interval [CI], 1.04-1.27; adjusted HR, 1.18; 95% CI, 1.03-1.27; P = .022) and worsening PAD status (unadjusted HR, 1.18; 95% CI, 1.13-1.31; adjusted HR, 1.17; 95% CI, 1.12-1.28; P < .001). Three-year Kaplan-Meier survival analysis demonstrated that patients with high FABP4 levels had a decreased freedom from MALE (75% vs 88%; log rank = 22.6; P < .001), vascular intervention (77% vs 89%; log rank = 20.8; P < .001), and worsening PAD status (87% vs 91%; log rank = 6.16; P = .013). ConclusionsIndividuals with higher serum concentrations of FABP4 are more likely to develop PAD-related adverse limb events. FABP4 has prognostic value in risk-stratifying patients for further vascular evaluation and management.

Structural Insights into Mouse H-FABP.

Intracellular fatty acid-binding proteins are evolutionarily highly conserved proteins. The major functions and responsibilities of this family are the regulation of FA uptake and intracellular transport. The structure of the H-FABP ortholog from mouse (Mus musculus) had not been revealed at the time this study was completed. Thus, further exploration of the structural properties of mouse H-FABP is expected to extend our knowledge of the model animal’s molecular mechanism of H-FABP function. Here, we report the high-resolution crystal structure and the NMR characterization of mouse H-FABP. Our work discloses the unique structural features of mouse H-FABP, offering a structural basis for the further development of small-molecule inhibitors for H-FABP.

Expression and single-nucleotide polymorphisms of the H-FABP gene in pigs

Heart fatty acid-binding protein (H-FABP) belongs to a family of intracellular fatty acid-binding proteins that are involved in the transport of long-chain fatty acids. Previous studies have indicated that H-FABP is significantly associated with intramuscular fat (IMF) content in pig. In this study, we compared the mRNA and protein expression of H-FABP between Tibetan pig (with high IMF) and Large White pig (with low IMF). The expression of H-FABP at both mRNA and protein levels in the tissues of backfat, longissimus dorsi muscle and liver was found to be significantly higher in TP than in LW. Single-nucleotide polymorphisms (SNPs) in a 2 kb region upstream of the start codon of the gene were screened using Sanger sequencing. We accordingly identified three SNPs (C-1375G, C-314T and T-158G) between the TP and LW populations and genotyped these based on PCR-restriction fragment length polymorphisms (PCF-RFLPs) analysis. The results showed that the C-1375G site might regulate H-FABP gene expression and thus be associated with fat deposition in pigs. Our study provides important data for further investigating the regulatory mechanism of H-FABP for fat deposition in pigs.

FABP5 is a critical regulator of methionine- and estrogen-induced SREBP-1c gene expression in bovine mammary epithelial cells.

The intracellular fatty acid-binding proteins (FABPs) are a well-conserved family that function as lipid chaperones. Ongoing studies are focused on identification of the mechanistic complexity and vast biological diversity of different isoforms of FABPs. However, the molecular mechanism of FABP5 in the regulation of milk fat synthesis in the mammary gland of dairy cows is still largely unknown. Here, we report that FABP5 acts as a critical regulator of terol response element-binding protein-1c (SREBP-1c) gene expression induced by methionine (Met) and estrogen (E2) in bovine mammary epithelial cells (BMECs). We observed that the expression of FABP5 was markedly higher in dairy cow mammary tissue during the lactating period than the puberty period and the dry period. FABP5 is located in the cytoplasm, and Met and E2 significantly increase the protein levels of FABP5 in BMECs. Using gene function study approaches, we revealed that FABP5 positively regulates SREBP-1c gene expression and promotes milk fat synthesis. We confirmed that FABP5 is required for Met- and E2-induced SREBP-1c gene expression and milk fat synthesis. We further uncovered that fatty acids are needed for FABP5-mediated SREBP-1c gene expression. Thus, our study demonstrates that FABP5 is a critical regulator of Met- and E2-induced SREBP-1c gene expression leading to milk fat synthesis.

A proteomic analyses to assess the effects of chronic exposure of bisphenol a to adult zebrafish (Danio rerio)

Bisphenol A (BPA) is an endocrine-disrupting compound found in the environment as well as in the plastic food containers for human use. Most impact of this compound to animals is acute toxicity to the liver of young individuals, but little is known about chronic toxicity to the adult liver. Here we report that, when adult zebrafish were exposed to various concentration of bisphenol A for 60 days, we have the number of liver protein spots in 2D-PAGE gels was reduced to 15-25%. Protein identification by HPLC-ESI (electron spray ionization) revealed that sixteen 2D-PAGE spots were remarkably altered and majority of them are related to metabolic energy system; e.g., liver basic L-lactate dehydrogenase B-B chain, ATP synthase subunit beta, and intracellular fatty acid-binding proteins. Besides, heat shock protein 60kDa 1 (HSPD1), which is known to associate with inflammation, was over-expressed in fish liver after exposure to 100 µg/l BPA, but not at lower concentrations of BPA. Thus, chronic exposure to environmental BPA may cause liver dysfunctions. Sixteen hepatic proteins identified in this study would be potential biomarkers for chronic BPA toxicity. Citation: Ngo Thi Mai, Do Hong Lan Chi, Le Phi Nga, 2017. A proteomic analyses to assess the effects of chronic exposure of bisphenol a to adult zebrafish (Danio rerio). Tap chi Sinh hoc, 39(3): 333-341. DOI: 10.15625/0866-7160/v39n3.98995. *Corresponding author: lephinga1@hotmail.com, lephinga@hcmut.edu.vn Received 12 December 2016, accepted 20 August 2017

Abstract P347: Retinol-binding Protein 7 (RBP7) is Required for PPARG-mediated Endothelial Protection via Adiponectin

PPARγ protects against endothelial dysfunction by regulation of unknown target genes. One such target, RBP7, an intracellular fatty acid-binding protein, exhibits endothelium-specific expression, but its effect on vascular function remain unknown. We hypothesize that RBP7 is endothelial protective. We examined vascular responses in basilar artery (pressurized myograph) of RBP7-knockout (KO) and wild type (WT) mice fed normal chow (ND) or high fat diet (HFD) for 8 wks. Endothelium-dependent acetylcholine (ACh)-induced relaxation was significantly impaired in HFD-fed KO mice (ACh, 100μM: 33±7% KO vs 83±10% WT, p&lt;0.05), but not in ND-fed groups. This response was ameliorated by pre-incubation with superoxide scavenger tempol (1mM) or PEG-superoxide dismutase (100 U/ml). Mean arterial pressure (measured by radiotelemetry), body weight, hepatic steatosis, fasting glucose, glucose tolerance, and insulin sensitivity were similar in HFD-fed KO and WT mice. To identify targets downstream of RBP7, RNA-Sequencing was performed on carotid arteries from 8-week HFD-fed WT and KO mice as well as ND-fed age-matched littermates. Adiponectin (AdipoQ), a PPARγ target, was increased ~6-fold in HFD-fed WT mice, a response that was markedly blunted in KO mice. RNA sequencing was confirmed by qPCR. There was no difference in plasma AdipoQ. AdipoQ protein is expressed in endothelial cells of carotid arteries and its level of expression was increased in HFD-fed WT but not KO mice (AdipoQ/CD31: 1.14±0.1 WT-HFD vs 0.82±0.1 WT-ND, p&lt;0.05; 0.79±0.1 KO-HFD vs 0.81±0.04 KO-ND). This led us to hypothesize that AdipoQ is involved in RBP7-mediated endothelial protection. Incubation of basilar artery with mouse full-length AdipoQ protein (5 μg/mL, 4 hours) significantly ameliorated endothelial dysfunction (ACh, 100 μM: 56±6% AdipoQ+KO vs 26±3% KO, p&lt;0.05) and blunted carotid artery superoxide production in HFD-fed KO mice. AdipoQ also protects against endothelial dysfunction caused by subpressor Ang-II in KO mice. We conclude that RBP7 protects the endothelium from oxidative stress-induced dysfunction through an AdipoQ-dependent mechanism. Our evidence suggests RBP7 is an essential cofactor for activation of some PPARγ target genes in the endothelium.

Fatty Acid-Binding Protein 5 Facilitates the Blood–Brain Barrier Transport of Docosahexaenoic Acid

The brain has a limited ability to synthesize the essential polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) from its omega-3 fatty acid precursors. Therefore, to maintain brain concentrations of this PUFA at physiological levels, plasma-derived DHA must be transported across the blood-brain barrier (BBB). While DHA is able to partition into the luminal membrane of brain endothelial cells, its low aqueous solubility likely limits its cytosolic transfer to the abluminal membrane, necessitating the requirement of an intracellular carrier protein to facilitate trafficking of this PUFA across the BBB. As the intracellular carrier protein fatty acid-binding protein 5 (FABP5) is expressed at the human BBB, the current study assessed the putative role of FABP5 in the brain endothelial cell uptake and BBB transport of DHA in vitro and in vivo, respectively. hFAPB5 was recombinantly expressed and purified from Escherichia coli C41(DE3) cells and the binding affinity of DHA to hFABP5 assessed using isothermal titration calorimetry. The impact of FABP5 siRNA on uptake of (14)C-DHA into immortalized human brain microvascular endothelial (hCMEC/D3) cells was assessed. An in situ transcardiac perfusion method was optimized in C57BL/6 mice and subsequently used to compare the BBB influx rate (Kin) of (14)C-DHA between FABP5-deficient (FABP5(-/-)) and wild-type (FABP5(+/+)) C57BL/6 mice. DHA bound to hFABP5 with an equilibrium dissociation constant of 155 ± 8 nM (mean ± SEM). FABP5 siRNA transfection decreased hCMEC/D3 mRNA and protein expression of FABP5 by 53.2 ± 5.5% and 44.8 ± 13.7%, respectively, which was associated with a 14.1 ± 2.7% reduction in (14)C-DHA cellular uptake. By using optimized conditions for the in situ transcardiac perfusion (a 1 min preperfusion (10 mL/min) followed by perfusion of (14)C-DHA (1 min)), the Kin of (14)C-DHA was 0.04 ± 0.01 mL/g/s. Relative to FABP5(+/+) mice, the Kin of (14)C-DHA decreased 36.7 ± 12.4% in FABP5(-/-) mice. This study demonstrates that FABP5 binds to DHA and is involved in the brain endothelial cell uptake and subsequent BBB transport of DHA, confirming the importance of this cytoplasmic carrier protein in the CNS exposure of this PUFA essential for neuronal function.

Fatty acid binding protein FABP3 from Chinese mitten crab Eriocheir sinensis participates in antimicrobial responses

Intracellular fatty acid-binding proteins (FABPs) are members of the lipid-binding protein superfamily. Aside from the main functions of FABPs in the uptake and transport of fatty acids, they are also critical in innate immunology. In this work, the full-length cDNA for a Chinese mitten crab Eriocheir sinensis FABP (Es-FABP3) was cloned with an open reading frame of 402 bp encoding a 133 amino acid polypeptide. Analysis using quantitative real-time PCR (qPCR) revealed that Es-FABP3 transcripts were widely distributed in gills, muscle, intestine, hepatopancreas, eyestalk, heart, stomach, brain, thoracic ganglia and hemocytes. After challenge with pathogen associated molecular pattern molecules (PAMPs), the relative mRNA expression levels of Es-FABP3 increased in hepatopancreas, gills and hemocytes. Moreover, the mature recombinant Es-FABP3 protein exhibited different binding activities to bacteria and fungus and inhibited the growth of different microbes. These collective results demonstrated the role of Es-FABP3 in the immunoreactions of E. sinensis to PAMPs.

High salinity induced expression profiling of differentially expressed genes in shrimp (Penaeus monodon).

Four suppression subtractive hybridization (SSH) cDNA libraries were constructed to identify differentially expressed salinity stress responsive genes of black tiger shrimp, Penaeus monodon exposed to high (55 ppt) salinity conditions. One each of the forward and reverse SSH cDNA libraries were developed from the gill and gut tissues of shrimp and clones having inserts larger than 300 bp were unidirectionally sequenced. Based on the sequence homology search, the identified genes were categorized for their putative functions related to a wide range of biological roles, such as nucleic acid regulation and replication, immune response, energy and metabolism, signal transduction, cellular process, structural and membrane proteins, stress and osmoregulation. Gene expression levels in response to high salinity conditions at 2 weeks post salinity stress for some of the differentially expressed genes (Na(+)/K(+)-ATPase α-subunit, glutathione peroxidase, intracellular fatty acid binding protein, elongation factor 2, 14-3-3 like protein, penaeidin, translationally controlled tumor protein, transglutaminase and serine proteinase inhibitor B3) identified from SSH cDNA libraries were analysed by real-time RT-PCR. The highest gene expression levels was observed for Na(+)/K(+)-ATPase α-subunit in gill tissues (15.23-folds) and antennal glands (12.01-folds) and intracellular fatty acid binding protein in gut tissues (14.05-folds) respectively. The differential and significant levels of gene expression indicate the functional role of these genes in shrimp salinity stress adaptive mechanisms.

Identification and expression analysis of differentially expressed genes from shrimp (Penaeus monodon) in response to low salinity stress

Four suppression subtractive hybridization (SSH) cDNA libraries were constructed to identify differentially expressed salinity stress responsive genes of black tiger shrimp, Penaeus monodon exposed to low (3 ppt) salinity conditions. Forward and reverse SSH cDNA libraries were developed from the gill and gut tissues of shrimp and clones having inserts larger than 300 bp were unidirectionally sequenced. Based on the sequence homology search, the identified genes were categorized for their putative functions related to a wide range of biological roles, such as nucleic acid regulation and replication, immune response, energy and metabolism, cell signaling, cellular process, cytoskeleton and membrane structure, stress and osmoregulation. Gene expression levels in response to low salinity conditions at 2 weeks post salinity stress of thirteen selected differentially expressed genes identified from SSH cDNA libraries (14-3-3 like protein, crustin, lysozyme, arginine kinase, Na+/K+-ATPase α-subunit, intracellular fatty acid binding protein, cathepsin B, anti-lipopolysaccharide factor, ferritin, ubiquitin conjugating enzyme E2, calreticulin, innexin 2 and heat shock protein 21) were analyzed by RT-PCR. The highest gene expression levels were observed for Na+/K+-ATPase α-subunit (34.28-folds) in gill tissues, intracellular fatty acid binding protein (13.30-folds) in gut tissues and innexin 2 (14.43-folds) in muscle tissues respectively. The differential and significant levels of gene expression indicate the functional role of these genes in shrimp salinity stress adaptive mechanisms.

CD36 Enhances Fatty Acid Uptake by Increasing the Rate of Intracellular Esterification but Not Transport across the Plasma Membrane

CD36 is a multifunctional protein that enhances cellular fatty acid (FA) uptake, a key step in energy metabolism, and its dysregulation in multiple tissue sites is central to obesity-linked diabetes, a risk factor for atherosclerosis. Although CD36 has been implicated in FA uptake in a correlative way, the molecular mechanisms are not known. Their elucidation in cells is confounded by receptor-mediated uptake of low-density lipoprotein by CD36 and the competitive and/or contributive effects of other proteins involved in FA transport and metabolism, which include caveolin(s), fatty acid transport protein (FATP), intracellular fatty acid binding protein, and enzymes involved in the conversion of FAs to esters. Here we utilized a simpler cellular system (HEK cells), which lack caveolin-1, CD36, and FATP and metabolize FAs slowly compared to the time frame of transmembrane FA movement. Our previous studies of HEK cells showed that caveolin-1 affects FA binding and translocation across the plasma membrane and but not FA esterification [Simard, J. R., et al. (2010) J. Lipid Res. 51 (5), 914-922]. Our key new finding is that CD36 accelerates FA uptake and extensive incorporation into triglycerides, a process that is slower (minutes) than transmembrane movement (seconds). Real-time fluorescence measurements showed that the rates of binding and transport of oleic acid into cells with and without CD36 were not different. Thus, CD36 enhances intracellular metabolism, i.e., esterification, and thereby increases the rate of FA uptake without catalyzing the translocation of FA across the plasma membrane, suggesting that CD36 is central to FA uptake via its effects on intracellular metabolism.

Molecular cloning and functional analysis of the fatty acid-binding protein (Sp-FABP) gene in the mud crab (Scylla paramamosain)

Intracellular fatty acid-binding proteins (FABPs) are multifunctional cytosolic lipid-binding proteins found in vertebrates and invertebrates. In this work, we used RACE to obtain a full-length cDNA of Sp-FABP from the mud crab Scylla paramamosain. The open reading frame of the full length cDNA (886 bp) encoded a 136 amino acid polypeptide that showed high homology with related genes from other species. Real-time quantitative PCR identified variable levels of Sp-FABP transcripts in epidermis, eyestalk, gill, heart, hemocytes, hepatopancreas, muscle, ovary, stomach and thoracic ganglia. In ovaries, Sp-FABP expression increased gradually from stage I to stage IV of development and decreased in stage V. Sp-FABP transcripts in the hepatopancreas and hemocytes were up-regulated after a bacterial challenge with Vibrio alginnolyficus. These results suggest that Sp-FABP may be involved in the growth, reproduction and immunity of the mud crab.

Distribution of adipocyte-related cells in skeletal muscle of rainbow trout Oncorhynchus mykiss

Adiponectin is one of the adipokines secreted mainly from adipocytes in mammals. In rainbow trout, however, adiponectin is highly expressed in skeletal muscle. Although it has been suggested that fish skeletal muscle contains adipocytes, their endocrine function and distribution are poorly understood. Recently, an EST analysis of rainbow trout found that heart-type fatty acid binding protein (H-FABP), a member of the intracellular fatty acid binding protein family, encodes an adipose-specific gene. In this study, we produced anti-adiponectin and H-FABP antibodies and investigated the distribution of adipocytes and related cells in skeletal muscle of rainbow trout. The adiponectin signal was detected at around 75 kDa in muscle in Western blotting. Since the molecular mass of rainbow trout adiponectin is around 25 kDa, this 75 kDa band would be a trimer. For H-FABP, the signal band was detected at around 15 kDa. Immunohistochemistry of skeletal muscle sections indicated that adiponectin and H-FABP signals were present outside of muscle cells and throughout the muscle tissues, suggesting the existence of adipocyte-related cells in these regions. These results will contribute to our understanding of energy metabolism in fish skeletal muscle.

A Photocytes-Associated Fatty Acid-Binding Protein from the Light Organ of Adult Taiwanese Firefly, Luciola cerata

BackgroundIntracellular fatty acid-binding proteins (FABPs) are considered to be an important energy source supplier in lipid metabolism; however, they have never been reported in any bioluminescent tissue before. In this study, we determined the structural and functional characteristics of a novel FABP (lcFABP) from the light organ of adult Taiwanese firefly, Luciola cerata, and showed anatomical association of lcFABP with photocytes.Principal FindingsOur results demonstrated the primary structure of lcFABP deduced from the cDNA clone of light organ shares structural homologies with other insect and human FABPs. In vitro binding assay indicated the recombinant lcFABP binds saturated long chain fatty acids (C14-C18) more strongly than other fatty acids and firefly luciferin. In addition, tissue distribution screening assay using a rabbit antiserum specifically against the N-terminal sequence of lcFABP confirmed the light organ-specific expression of lcFABP. In the light organ, the lcFABP constituted about 15% of total soluble proteins, and was detected in both cytosol and nucleus of photocytes.ConclusionsThe specific localization of abundant lcFABP in the light organ suggests that sustained bioluminescent flashes in the light organ might be a high energy demanding process. In photocytes, lcFABP might play a key role in providing long chain fatty acids to peroxisomes for the luciferase-catalyzed long chain acyl-CoA synthetic reaction.

Tissue-specific Functions in the Fatty Acid-binding Protein Family

The intracellular fatty acid-binding proteins (FABPs) are abundantly expressed in almost all tissues. They exhibit high affinity binding of a single long-chain fatty acid, with the exception of liver FABP, which binds two fatty acids or other hydrophobic molecules. FABPs have highly similar tertiary structures consisting of a 10-stranded antiparallel β-barrel and an N-terminal helix-turn-helix motif. Research emerging in the last decade has suggested that FABPs have tissue-specific functions that reflect tissue-specific aspects of lipid and fatty acid metabolism. Proposed roles for FABPs include assimilation of dietary lipids in the intestine, targeting of liver lipids to catabolic and anabolic pathways, regulation of lipid storage and lipid-mediated gene expression in adipose tissue and macrophages, fatty acid targeting to β-oxidation pathways in muscle, and maintenance of phospholipid membranes in neural tissues. The regulation of these diverse processes is accompanied by the expression of different and sometimes multiple FABPs in these tissues and may be driven by protein-protein and protein-membrane interactions.

Localization of fatty acid binding proteins (FABPs) in the cochlea of mice

Various fatty acids (FAs) are involved in many different functions in the organism as a source of energy, as essential ingredients of membranous lipids as well as intracellular signaling molecules. Intracellular fatty acid binding proteins (FABPs) comprise a family of soluble lipid binding proteins with low molecular masses and which can make long chain FAs soluble to allow intracellular translocation in the aqueous cytosol. To clarify the possible involvement of FAs and FABPs in hearing function, the present study investigated the localization of FABPs in the cochlea of adult mice using immunohistochemical procedures. Among various FABP species, H (heart-type)-FABP was localized in inner and outer pillar cells and outer phalangeal cells, while B (brain-type)-FABP was localized in border cells and cells of Hensen, and fibrocytes in the spiral limbus and spiral prominence. In the spiral ganglion, moderate to low H-FABP immunoreactivity was observed in almost all neurons, while B-FABP immunoreactivity was found in satellite cells. The discrete localization of the two FABPs in different non-receptor cells in the Organ of Corti suggests that the FABP species and/or their ligands, FAs, play important roles in the regulation of the hearing function.

Abstract 56: Differential expression of fatty-acid-binding proteins 3 and 5 among African American and Caucasian women with breast cancer

Abstract Breast cancer is a major cause of mortality among middle-aged and elderly women. It is well documented that African-American (AA) patients tend to present with more advanced states of breast cancer and have lower survival rates than Caucasian-Americans (CA). Additionally, the age specific breast cancer incidence rate for AA women under age 35 is greater than twice the rate for CA of similar age, and the mortality rate is more than three times greater. Some of this disparity is due to socioeconomic factors; however, biological factors may also be involved. Altered expression of intracellular fatty-acid binding proteins (FABPs) has been implicated in the progression of breast cancer. FABP3 (heart/muscle type), also known as mammary-derived growth inhibitor (MDGI), is associated with differentiation of breast tissue, and is downregulated in breast cancer tissues. FABP5 (epidermal type) is upregulated in breast cancer tissues as a possible compensation for FABP3's decrease. Therefore, we hypothesized that AA malignant breast tissue samples would contain lower levels of FABP3, and higher levels of compensatory FABP5. We determined levels of the aforementioned proteins and the corresponding mRNA in paired breast tissue samples from AA and CA women by Western blot analysis and RT-PCR. Data was divided into three groups- ages 17-45, ages 45-65, and ages 66 and up. In ages 17-45, FABP3 protein levels were higher in AA malignant tissues relative to CA malignant, and FABP5 protein levels were similar between racial groups. Also, FABP3 levels were decreased in AA malignant tissues compared to AA normal. In ages 46-65, levels of FABP3 protein, and of FABP5 protein and mRNA, were higher in AA malignant tissues relative to CA malignant. Furthermore, FABP3 protein levels were increased in AA malignant tissues relative to AA normal tissues. In ages 66 and up, levels of both FABPs were similar between AA malignant and CA malignant tissues. However, mRNA levels of both FABPs were significantly increased in the CA malignant tissues compared to AA malignant. In addition, levels of FABP3 and FABP5 were increased in the AA malignant tissues relative to the AA normal tissues. Thus, it appears that the conventional knowledge regarding FABP3 downregulation in breast cancer may only apply to AA cancer patients below age 45. Furthermore, in ages above 66, AA breast cancer patients are at a significant disadvantage compared to their CA counterparts, as it relates to expression of FABPs 3 and 5. Further study is needed to elucidate the mechanisms involved in this differential FABP expression pattern between the racial groups, and its implication on the survival disparity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 56.

Liver Fatty Acid Binding Protein (L-FABP) as a Target for the Prevention of High Fat Diet Induced Obesity and Hepatic Steatosis

An epidemic of obesity, fueled in large part by increased consumption of diets enriched in saturated fat, has heightened interest in the pathways and mechanisms that modulate the uptake and utilization of individual dietary lipid components. Emerging evidence has implicated members of the intracellular fatty acid binding protein (FABP) multigene family as important metabolic sensors that may regulate substrate trafficking and metabolic compartmentalization. Among these, liver fatty acid binding protein (L-FABP, Fabp1) is an abundant cytosolic protein expressed in both mammalian small intestinal enterocytes and hepatocytes. L-Fabp -/- mice were protected against hepatic steatosis following a prolonged fast, suggesting a role in modulating hepatic FA trafficking in response to augmented lipid mobilization from adipose stores. In addition, L-Fabp -/- mice are protected against obesity and hepatic steatosis when fed a high saturated fat diet or a high saturated fat diet containing cholesterol (ie Western diet), but not when fed a high fat diet containing polyunsaturated fat. These findings imply substrate specificity in the lipid sensing functions of L-FABP. Together the data suggest that L-FABP regulates elements of both intestinal and hepatic FA trafficking as well as cholesterol metabolism and in turn exerts an important role in the pathogenesis of diet- induced obesity and hepatic steatosis through specific diet- gene interactions.

Identification of differentially expressed genes in haemocytes of the crayfish ( Procambarus clarkii) infected with white spot syndrome virus by suppression subtractive hybridization and cDNA microarrays

By using suppression subtractive hybridization (SSH) and cDNA microarrays, we studied the differentially expressed genes in haemocytes of the crayfish ( Procambarus clarkii) infected with white spot syndrome virus (WSSV). Thirty three differentially expressed genes were detected in which 31 were up-regulated and 2 were down-regulated. The up-regulated genes include serine protease inhibitors, chaperonin, synaptasome-associated protein of 25 kD(SNAP25), tubulin, zinc-finger protein, intracellular fatty acid binding protein, extracellular superoxide dismutase precursor, arginine kinase, 70 kD heat shock like protein and Bax inhibitor-1. A lot of genes including the 2 down-regulated genes are still unknown. All these immuno-related genes responding to the virus infection provide a new insight for further study in the shrimp innate immunity.

Gene expression of fatty acid-binding proteins, fatty acid transport proteins (cd36 and FATP) and β-oxidation-related genes in Atlantic salmon (Salmo salarL.) fed fish oil or vegetable oil

Relative gene expression pattern of fatty acid transport proteins (FATP and cd36), intracellular fatty acid-binding proteins (FABP3, FABP10 and FABP11), β-oxidation-related genes [carnitine palmitoyl transferase II (CPTII), peroxisome proliferator-activated receptor β (PPARβ), acyl-CoA oxidase (AOX), long-chain fatty acyl-CoA synthetase (FACS), acyl-CoA dehydrogenase (dehydrogenase)] and uncoupling protein 2 (UCP2) was assessed by RT-qPCR in Atlantic salmon muscle (red and white), liver, heart, myosepta and visceral fat. FABP11, a FABP isoform not previously described in Atlantic salmon, was highly expressed in visceral fat and myosepta and at the lower level in red muscle, white muscle, myosepta and heart. Furthermore, Atlantic salmon were fed either a diet containing fish oil (FO) or a complete replacement of FO with a vegetable oil blend (55% rapeseed oil, 30% palm oil and 15% linseed oil; VO) for the production cycle (27 months from start of feeding and until ∼4.5 kg mean weight). The expression of genes related to β-oxidation, fatty acid uptake and transport in the white muscle indicate (n = 3) significant down-regulation in VO fed Atlantic salmon and correlated with previously reported white muscle triacylglycerol stores and β-oxidation. FABP11 in visceral fat and myosepta was also down-regulated in VO fed fish.