scholarly journals Unconventional Secretion of Adipocyte Fatty Acid Binding Protein 4 Is Mediated By Autophagic Proteins in a Sirtuin-1–Dependent Manner

Diabetes ◽  
2019 ◽  
Vol 68 (9) ◽  
pp. 1767-1777 ◽  
Author(s):  
Ajeetha Josephrajan ◽  
Ann V. Hertzel ◽  
Ellie K. Bohm ◽  
Michael W. McBurney ◽  
Shin-Ichiro Imai ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Sirtuin 1 ◽  
Dependent Manner ◽  
Fatty Acid Binding ◽  
Acid Binding Protein ◽  
Unconventional Secretion ◽  
Autophagic Proteins

Inhibition of binding to fatty acid binding protein reduces the intracellular transport of fatty acids

1996 ◽  
Vol 271 (1) ◽  
pp. G113-G120 ◽  
Author(s):  
B. A. Luxon
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Intracellular Transport ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Female Rats ◽  
Dependent Manner ◽  
Fatty Acid Binding ◽  
Acid Binding Protein ◽  
Cytoplasmic Transport

Male livers, containing lesser amounts of fatty acid binding protein (FABP), utilize fatty acids more slowly than female livers. Conventional wisdom dictates that FABP stimulates fatty acid use by increasing cytoplasmic transport rates. Previously, we showed that the cytoplasmic diffusion of a fatty acid analogue [12-N-methyl-7-nitrobenzo-2-oxa-1,3-diazol-amino stearate (NBD-stearate)] is faster in female hepatocytes, paralleling the larger amounts of FABP. Sex differences in other cytoplasmic factors could also lead to faster diffusion, independent of FABP levels. The aim of this study was to determine the effect of inhibition of fatty acid binding to FABP on the directly measured intracellular transport rate of NBD-stearate. The binding of NBD-stearate to FABP was reduced by incubating hepatocytes isolated from male and female rats with alpha-bromo-palmitate (0-1,500 microM), a modified long-chain fatty acid that binds to FABP. The inhibition by alpha-bromo-palmitate on NBD-stearate binding to FABP was measured with the use of centrifugation to separate cytosol from cytoplasmic membranes. Laser photobleaching (fluorescence recovery after photobleaching) was used to measure the cytoplasmic diffusion of NBD-stearate in hepatocytes. Alpha-Bromo-palmitate incubation reduced NBD-stearate binding to FABP in a dose-dependent manner. The measured diffusion rate was also reduced in proportion to the degree of binding inhibition. We conclude that cytoplasmic transport of NBD-stearate is modulated by binding to soluble proteins like FABP. FABP enhances diffusive transport by reducing binding to immobile cytosolic membranes.

scholarly journals Chain length of dietary fatty acids determines gastrointestinal motility and visceromotor function in mice in a fatty acid binding protein 4-dependent manner

2019 ◽  
Vol 59 (6) ◽  
pp. 2481-2496
Author(s):  
Paula Mosińska ◽  
Adrian Szczepaniak ◽  
Tatiana Wojciechowicz ◽  
Marek Skrzypski ◽  
Krzysztof Nowak ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Binding Protein ◽  
Visceral Pain ◽  
Binding Protein ◽  
Dietary Fatty Acids ◽  
Dependent Manner ◽  
Fatty Acid Binding ◽  
Acid Binding Protein ◽  
Gi Motility

Abstract Purpose We hypothesize that different types of dietary fatty acids (FAs) affect gastrointestinal (GI) motility and visceromotor function and that this effect can be regulated by the fatty acid binding protein 4 (FABP4). Methods Mice were fed for 60 days with standard diet (STD), STD with 7% (by weight) coconut oil, rich in medium-chain FAs (MCFAs) (COCO), or with 7% evening primrose oil, rich in long-chain FAs (LCFAs) (EPO). In each group, half of the mice received FABP4 inhibitor, BMS309403 (1 mg/kg; i.p.) twice a week. Body weight (BW) and food intake were measured; well-established tests were performed to characterize the changes in GI motility and visceral pain. White adipose tissue and colonic samples were collected for cell culturing and molecular studies. Results COCO significantly increased GI transit, but not colonic motility. COCO and EPO delayed the onset of diarrhea, but none affected the effect of loperamide. EPO reduced BW and increased the visceromotor response (VMR) to colorectal distension (CRD). COCO and EPO reduced differentiation of preadipocytes. Treatment with BMS309403: (1) reversed the effects induced by COCO in physiological conditions and in mouse models of diarrhea; (2) prevented the effects of EPO on BW, VMR to CRD and castor oil-induced diarrhea; (3) affected proliferation of preadipocytes; (4) changed the expression of Fabp4 in colonic and adipocyte samples from COCO and EPO. Conclusion Modifying dietary intake of MCFAs and LCFAs may be used to control GI motility or visceral pain and thus modulate the symptoms of functional GI disorders. The effect is dependent on the expression of FABP4.

scholarly journals Fatty acid-binding protein 5 regulates diet-induced obesity via GIP secretion from enteroendocrine K cells in response to fat ingestion

2015 ◽  
Vol 308 (7) ◽  
pp. E583-E591 ◽  
Author(s):  
Kimitaka Shibue ◽  
Shunsuke Yamane ◽  
Norio Harada ◽  
Akihiro Hamasaki ◽  
Kazuyo Suzuki ◽  
...  
Keyword(s):  
Oleic Acid ◽  
Fatty Acid ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Whole Body ◽  
Dependent Manner ◽  
Fatty Acid Binding ◽  
Acid Binding Protein ◽  
K Cells ◽  
Diet Induced Obesity

Gastric inhibitory polypeptide (GIP) is an incretin released from enteroendocrine K cells in response to nutrient intake, especially fat. GIP is one of the contributing factors inducing fat accumulation that results in obesity. A recent study shows that fatty acid-binding protein 5 (FABP5) is expressed in murine K cells and is involved in fat-induced GIP secretion. We investigated the mechanism of fat-induced GIP secretion and the impact of FABP5-related GIP response on diet-induced obesity (DIO). Single oral administration of glucose and fat resulted in a 40% reduction of GIP response to fat but not to glucose in whole body FABP5-knockout (FABP5−/−) mice, with no change in K cell count or GIP content in K cells. In an ex vivo experiment using isolated upper small intestine, oleic acid induced only a slight increase in GIP release, which was markedly enhanced by coadministration of bile and oleic acid together with attenuated GIP response in the FABP5−/− sample. FABP5−/− mice exhibited a 24% reduction in body weight gain and body fat mass under a high-fat diet compared with wild-type (FABP5+/+) mice; the difference was not observed between GIP-GFP homozygous knock-in (GIPgfp/gfp)-FABP5+/+ mice and GIPgfp/gfp-FABP5−/− mice, in which GIP is genetically deleted. These results demonstrate that bile efficiently amplifies fat-induced GIP secretion and that FABP5 contributes to the development of DIO in a GIP-dependent manner.

scholarly journals Unconventional Secretion of Adipocyte Fatty Acid Binding Protein (FABP4) by Adipocytes

2018 ◽  
Vol 32 (S1) ◽  
Author(s):  
Ajeetha Josephrajan ◽  
Ann V. Hertzel ◽  
Douglas Mashek ◽  
Do‐Hyung Kim ◽  
Shin‐Ichiro Imai ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Fatty Acid Binding ◽  
Acid Binding Protein ◽  
Unconventional Secretion

scholarly journals Intermedin Inhibits the Ox-LDL–Induced Inflammation in RAW264.7 Cells by Affecting Fatty Acid–Binding Protein 4 Through the PKA Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Kai Liu ◽  
Rufeng Shi ◽  
Si Wang ◽  
Qi Liu ◽  
Hengyu Zhang ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Biological Activities ◽  
Dependent Manner ◽  
Fatty Acid Binding ◽  
Acid Binding Protein ◽  
Raw264.7 Macrophages ◽  
Tnf Α ◽  
Pka Pathway

Objectives: Macrophages stimulated by oxidized low-density lipoprotein (ox-LDL) play an important role in the occurrence and progression of atherosclerosis. Fatty acid–binding protein 4 (FABP4), mainly existing in macrophages and adipocytes, can influence lipid metabolism and inflammation regulated by macrophages. Herein, we first established the connection between intermedin (IMD: a new peptide that has versatile biological activities in the cardiovascular system) and FABP4 and then investigated the influence of IMD on ox-LDL-induced changes in RAW264.7 macrophages line.Methods: The bioinformatics analysis, such as gene ontology enrichment and protein–protein interactions, was performed. For ox-LDL–stimulated assays, RAW264.7 was first pretreated with IMD and then exposed to ox-LDL. To explore the cell signaling pathways of IMD on inflammatory inhibition, main signaling molecules were tested and then cells were co-incubated with relevant inhibitors, and then exposed/not exposed to IMD. Finally, cells were treated with ox-LDL. The protein and gene expression of FABP4, IL-6, and TNF-α were quantified by WB/ELISA and RT-qPCR.Results: In the ox-LDL-stimulated assays, exposure of the RAW264.7 macrophages line to ox-LDL reduced cell viability and increased the expression of FABP4, as well as induced the release of IL-6 and TNF-α (all p < 0.05). On the other hand, IMD prevented ox-LDL–induced cell toxicity, FABP4 expression, and the inflammatory level in RAW264.7 (all p < 0.05) in a dose-dependent manner. The inhibition of FABP4 and the anti-inflammatory effect of IMD were partially suppressed by the protein kinase A (PKA) inhibitor H-89.Conclusion: IMD can prevent ox-LDL–induced macrophage inflammation by inhibiting FABP4, whose signaling might partially occur via the PKA pathway.

Calcium-dependent release of adipocyte fatty acid binding protein from human adipocytes

2014 ◽  
Vol 122 (03) ◽  
Author(s):  
I Schlottmann ◽  
M Ehrhart-Bornstein ◽  
M Wabitsch ◽  
SR Bornstein ◽  
V Lamounier-Zepter
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Human Adipocytes ◽  
Fatty Acid Binding ◽  
Calcium Dependent ◽  
Acid Binding Protein
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