804 FATTY ACID BINDING PROTEIN 4 INHIBITOR INHIBITS PANCREATIC CANCER GROWTH IN VITRO AND IN VIVO.

AbstractThe intestinal barrier plays a crucial role in maintaining gut health, and an increased permeability has been linked to several intestinal and extra-intestinal disorders. There is an increasing demand for interventions aimed at strengthening this barrier and for in vivo challenge models to assess their efficiency. This study investigated the effect of sauna-induced dehydration on intestinal barrier function (clinicaltrials.gov: NCT03620825). Twenty healthy subjects underwent three conditions in random order: (1) Sauna dehydration (loss of 3% body weight), (2) non-steroidal anti-inflammatory drug (NSAID) intake, (3) negative control. Intestinal permeability was assessed by a multi-sugar urinary recovery test, while intestinal damage, bacterial translocation and cytokines were assessed by plasma markers. The sauna dehydration protocol resulted in an increase in gastroduodenal and small intestinal permeability. Presumably, this increase occurred without substantial damage to the enterocytes as plasma intestinal fatty acid-binding protein (I-FABP) and liver fatty acid-binding protein (L-FABP) were not affected. In addition, we observed significant increases in levels of lipopolysaccharide-binding protein (LBP), IL-6 and IL-8, while sCD14, IL-10, IFN-ɣ and TNF-α were not affected. These results suggest that sauna dehydration increased intestinal permeability and could be applied as a new physiological in vivo challenge model for intestinal barrier function.

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Fatty Acid-Binding Protein 3 is Critical for α-Synuclein Uptake and MPP+-Induced Mitochondrial Dysfunction in Cultured Dopaminergic Neurons

International Journal of Molecular Sciences ◽

10.3390/ijms20215358 ◽

2019 ◽

Vol 20 (21) ◽

pp. 5358 ◽

Cited By ~ 9

Author(s):

Ichiro Kawahata ◽

Luc Bousset ◽

Ronald Melki ◽

Kohji Fukunaga

Keyword(s):

Fatty Acid ◽

Mitochondrial Dysfunction ◽

Dopaminergic Neurons ◽

Fatty Acid Binding Protein ◽

Neuronal Degeneration ◽

Binding Protein ◽

Mitochondrial Activity ◽

Fatty Acid Binding ◽

Acid Binding Protein

α-Synuclein is an abundant neuronal protein that accumulates in insoluble inclusions in Parkinson′s disease and other synucleinopathies. Fatty acids partially regulate α-Synuclein accumulation, and mesencephalic dopaminergic neurons highly express fatty acid-binding protein 3 (FABP3). We previously demonstrated that FABP3 knockout mice show decreased α-Synuclein oligomerization and neuronal degeneration of tyrosine hydroxylase (TH)-positive neurons in vivo. In this study, we newly investigated the importance of FABP3 in α-Synuclein uptake, 1-methyl-4-phenylpyridinium (MPP+)-induced axodendritic retraction, and mitochondrial dysfunction. To disclose the issues, we employed cultured mesencephalic neurons derived from wild type or FABP3−/− C57BL6 mice and performed immunocytochemical analysis. We demonstrated that TH+ neurons from FABP3+/+ mice take up α-Synuclein monomers while FABP3−/− TH+ neurons do not. The formation of filamentous α-Synuclein inclusions following treatment with MPP+ was observed only in FABP3+/+, and not in FABP3−/− neurons. Notably, detailed morphological analysis revealed that FABP−/− neurons did not exhibit MPP+-induced axodendritic retraction. Moreover, FABP3 was also critical for MPP+-induced reduction of mitochondrial activity and the production of reactive oxygen species. These data indicate that FABP3 is critical for α-Synuclein uptake in dopaminergic neurons, thereby preventing synucleinopathies, including Parkinson′s disease.

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Studies on the effect of an heterologous fatty acid-binding protein on acyl-CoA oxidase induction in Saccharomyces cerevisiae

Biochemical Journal ◽

10.1042/bj3010615 ◽

1994 ◽

Vol 301 (2) ◽

pp. 615-620 ◽

Cited By ~ 7

Author(s):

I Smaczyńska ◽

M Skoneczny ◽

A Kurlandzka

Keyword(s):

Saccharomyces Cerevisiae ◽

Oleic Acid ◽

Fatty Acid ◽

Fatty Acid Binding Protein ◽

Binding Protein ◽

Yeast Cells ◽

Fatty Acid Binding ◽

Acid Binding Protein ◽

Acyl Coa Oxidase

The participation of fatty acid-binding protein (FABP) in the induction of peroxisomal beta-oxidation of fatty acids was investigated in vivo in an heterologous system. Bovine heart FABP was expressed in Saccharomyces cerevisiae under the control of two different promoters: a constitutive one and an oleic acid-inducible one. Constructs were introduced into yeast cells on multicopy and integrating plasmids. The heterologous FABP was present in yeast cells in two isoforms having pI values of about 5 and was able to bind oleic acid. The heterologous FABP had no significant effect on acyl-CoA oxidase activity at various concentrations of the inducing agent.

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Giardiasis Alters Intestinal Fatty Acid Binding Protein (I-FABP) and Plasma Cytokines Levels in Children in Brazil

Pathogens ◽

10.3390/pathogens9010007 ◽

2019 ◽

Vol 9 (1) ◽

pp. 7

Author(s):

Tiara Cascais-Figueiredo ◽

Phelipe Austriaco-Teixeira ◽

Maria Fantinatti ◽

Maria Luciana Silva-Freitas ◽

Joanna Reis Santos-Oliveira ◽

...

Keyword(s):

Fatty Acid ◽

Low Income ◽

Fatty Acid Binding Protein ◽

Binding Protein ◽

Developed Countries ◽

Mucosal Barrier ◽

Fatty Acid Binding ◽

Epithelial Damage ◽

Acid Binding Protein

Giardiasis is an intestinal infection caused by ingestion of water or food contaminated with cysts of Giardia lamblia. Susceptibility is higher in children and overall prevalence can reach up to 90% in low-income areas, although outbreaks are also reported in developed countries. Both parasite and immune-mediated epithelial damage has been observed in vitro and in animal models. However, whether enterocytes are directly damaged during infection is not entirely known. Our goal was to identify whether plasma levels of intestinal fatty acid binding protein (I-FABP), a marker of enterocyte damage, are related to the immune response in giardiasis. Blood plasma was collected from 31 children (19 Giardia-positive) from a public day care in Rio de Janeiro, Brazil. The levels of I-FABP were increased in Giardia-infected children compared to children without detectable infection. There was no difference in I-FABP levels in giardiasis caused by different genetic assemblages of Giardia. Levels of IL-8 were decreased, while there was a trend to elevated IL-17 in the Giardia-positive children. A positive correlation was observed between I-FABP and IL-17 levels as well as TNF, suggesting that epithelial damage can be related to cytokine production during giardiasis. These results help elucidate the relationship between the disruption of the intestinal mucosal barrier and immune responses to G. lamblia in children.

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Docetaxel/cabazitaxel and fatty acid binding protein 5 inhibitors produce synergistic inhibition of prostate cancer growth

The Prostate ◽

10.1002/pros.23921 ◽

2019 ◽

Vol 80 (1) ◽

pp. 88-98 ◽

Cited By ~ 4

Author(s):

Gregory Carbonetti ◽

Cynthia Converso ◽

Timothy Clement ◽

Changwei Wang ◽

Lloyd C Trotman ◽

...

Keyword(s):

Prostate Cancer ◽

Fatty Acid ◽

Fatty Acid Binding Protein ◽

Binding Protein ◽

Cancer Growth ◽

Fatty Acid Binding ◽

Synergistic Inhibition ◽

Acid Binding Protein

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Heart-type fatty acid-binding protein reciprocally regulates glucose and fatty acid utilization during exercise

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00287.2004 ◽

2005 ◽

Vol 288 (2) ◽

pp. E292-E297 ◽

Cited By ~ 16

Author(s):

Jane Shearer ◽

Patrick T. Fueger ◽

Jeffrey N. Rottman ◽

Deanna P. Bracy ◽

Bert Binas ◽

...

Keyword(s):

Fatty Acid ◽

Fatty Acid Binding Protein ◽

Binding Protein ◽

Whole Body ◽

Metabolic Clearance ◽

Fatty Acid Binding ◽

Nonesterified Fatty Acids ◽

Acid Binding Protein

The role of heart-type cytosolic fatty acid-binding protein (H-FABP) in mediating whole body and muscle-specific long-chain fatty acid (LCFA) and glucose utilization was examined using exercise as a phenotyping tool. Catheters were chronically implanted in a carotid artery and jugular vein of wild-type (WT, n = 8), heterozygous (H-FABP+/−, n = 8), and null (H-FABP−/−, n = 7) chow-fed C57BL/6J mice, and mice were allowed to recover for 7 days. After a 5-h fast, conscious, unrestrained mice were studied during 30 min of treadmill exercise (0.6 mph). A bolus of [125I]-15-( p-iodophenyl)-3- R, S-methylpentadecanoic acid and 2-deoxy-[3H]glucose was administered to obtain rates of whole body metabolic clearance (MCR) and indexes of muscle LCFA (Rf) and glucose (Rg) utilization. Fasting, nonesterified fatty acids (mM) were elevated in H-FABP−/− mice (2.2 ± 0.9 vs. 1.3 ± 0.1 and 1.3 ± 0.2 for WT and H-FABP+/−). During exercise, blood glucose (mM) increased in WT (11.7 ± 0.8) and H-FABP+/− (12.6 ± 0.9) mice, whereas H-FABP−/− mice developed overt hypoglycemia (4.8 ± 0.8). Examination of tissue-specific and whole body glucose and LCFA utilization demonstrated a dependency on H-FABP with exercise in all tissues examined. Reductions in H-FABP led to decreasing exercise-stimulated Rf and increasing Rg with the most pronounced effects in heart and soleus muscle. Similar results were seen for MCR with decreasing LCFA and increasing glucose clearance with declining levels of H-FABP. These results show that, in vivo, H-FABP has reciprocal effects on glucose and LCFA utilization and whole body fuel homeostasis when metabolic demands are elevated by exercise.

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