Showing papers on "Fatty acid-binding protein published in 2011"
TL;DR: FABPs demonstrate strong evolutionary conservation and are present in a spectrum of species including Drosophila melanogaster, Caenorhabditis elegans, mouse and human, and the most recently identified family member, FABP12, has been less studied.
Abstract: Fatty acid-binding proteins (FABPs) are members of the intracellular lipid-binding protein (iLBP) family and are involved in reversibly binding intracellular hydrophobic ligands and trafficking them throughout cellular compartments, including the peroxisomes, mitochondria, endoplasmic reticulum and nucleus. FABPs are small, structurally conserved cytosolic proteins consisting of a water-filled, interior-binding pocket surrounded by ten anti-parallel beta sheets, forming a beta barrel. At the superior surface, two alpha-helices cap the pocket and are thought to regulate binding. FABPs have broad specificity, including the ability to bind long-chain (C16-C20) fatty acids, eicosanoids, bile salts and peroxisome proliferators. FABPs demonstrate strong evolutionary conservation and are present in a spectrum of species including Drosophila melanogaster, Caenorhabditis elegans, mouse and human. The human genome consists of nine putatively functional protein-coding FABP genes. The most recently identified family member, FABP12, has been less studied.
342 citations
01 Jan 2011
TL;DR: Fatty acid-binding proteins (FABP) as discussed by the authors are members of the intracellular lipid-binding protein (iLBP) family and are involved in reversibly binding intra-cell hydrophobic ligands and trafficking them throughout cellular compartments, including peroxisomes, mitochondria, endoplasmic reticulum and nucleus.
Abstract: Fatty acid-binding proteins (FABPs) are members of the intracellular lipid-binding protein (iLBP) family and are involved in reversibly binding intracellular hydrophobic ligands and trafficking them throughout cellular compartments, including the peroxisomes, mitochondria, endoplasmic reticulum and nucleus. FABPs are small, structurally conserved cytosolic proteins consisting of a water-filled, interior-binding pocket surrounded by ten anti-parallel beta sheets, forming a beta barrel. At the superior surface, two alpha-helices cap the pocket and are thought to regulate binding. FABPs have broad specificity, including the ability to bind long-chain (C16‐C20) fatty acids, eicosanoids, bile salts and peroxisome proliferators. FABPs demonstrate strong evolutionary conservation and are present in a spectrum of species including Drosophila melanogaster, Caenorhabditis elegans, mouse and human. The human genome consists of nine putatively functional protein-coding FABP genes. The most recently identified family member, FABP12, has been less studied.
239 citations
TL;DR: In this paper, Fatty acid transport proteins (FATPs) were identified in the brain microvessel endothelial cells and characterized their involvement in fatty acid transport across an in vitro BBB model.
Abstract: The blood-brain barrier (BBB), formed by the brain capillary endothelial cells, provides a protective barrier between the systemic blood and the extracellular environment of the CNS. Passage of fatty acids from the blood to the brain may occur either by diffusion or by proteins that facilitate their transport. Currently several protein families have been implicated in fatty acid transport. The focus of the present study was to identify the fatty acid transport proteins (FATPs) expressed in the brain microvessel endothelial cells and characterize their involvement in fatty acid transport across an in vitro BBB model. The major fatty acid transport proteins expressed in human brain microvessel endothelial cells (HBMEC), mouse capillaries and human grey matter were FATP-1, -4 and fatty acid binding protein 5 and fatty acid translocase/CD36. The passage of various radiolabeled fatty acids across confluent HBMEC monolayers was examined over a 30-min period in the presence of fatty acid free albumin in a 1 : 1 molar ratio. The apical to basolateral permeability of radiolabeled fatty acids was dependent upon both saturation and chain length of the fatty acid. Knockdown of various fatty acid transport proteins using siRNA significantly decreased radiolabeled fatty acid transport across the HBMEC monolayer. Our findings indicate that FATP-1 and FATP-4 are the predominant fatty acid transport proteins expressed in the BBB based on human and mouse expression studies. While transport studies in HBMEC monolayers support their involvement in fatty acid permeability, fatty acid translocase/CD36 also appears to play a prominent role in transport of fatty acids across HBMEC.
236 citations
TL;DR: The putative or identified proteins participating in the intestinal uptake, intracellular transport and basolateral secretion of these fat-soluble vitamins and carotenoids are focused on, and the uncertainties that need to be explored in the future are outlined.
188 citations
TL;DR: The hypothesis that hyperlipidemia and hyperinsulinemia regulate lipid content and expression of lipid-trafficking proteins in human placental trophoblasts is tested and suggests that FABP4 is essential for trophoblast lipid accumulation.
Abstract: Context: Maternal obesity, gestational diabetes (GDM), or type 2 diabetes (T2DM) is associated with altered lipid metabolism and fetal overgrowth. Objective: The objective of the study was to test the hypothesis that hyperlipidemia and hyperinsulinemia regulate lipid content and expression of lipid-trafficking proteins in human placental trophoblasts. Study Design: Pregnant women were prospectively enrolled for clinical specimens collection, and cultured human trophoblasts were used for experiments. Setting: This was a translational study conducted at an academic biomedical research center. Patients or Other Participants: Normal weight, obese, or obese with gestational diabetes or type 2 diabetes pregnant women (n = 10 in each group) undergoing scheduled cesarean delivery at term were enrolled. Interventions: Cultured primary human trophoblasts, exposed to insulin (10 nm) and/or fatty acids mix (1200 μm) in the absence or presence of an fatty acid binding protein 4 (FABP4) inhibitor or after small interfe...
110 citations
TL;DR: It is demonstrated that the heart-type fatty acid-binding protein, FABP3, is essential for cold tolerance and efficient fatty acid oxidation in mouse brown adipose tissue, despite the abundant expression of adipose-type fat-bindingprotein, F ABP4 (also known as aP2).
83 citations
TL;DR: Hesperidin may improve hypercholesterolemia and fatty liver by inhibiting both the synthesis and absorption of cholesterol and regulating the expression of mRNA for RBP, C-FABP, and H-F ABP.
82 citations
76 citations
TL;DR: This work shows that the novel small-molecule activators of AMPK (RSVA314 and RSVA405) are potent inhibitors of adipogenesis and thus may have therapeutic potential against obesity.
Abstract: AMP-activated protein kinase (AMPK) is a sensor and regulator of cellular energy metabolism potentially Implicated In a broad range of conditions, including obesity and Alzheimer’s disease. Its role in the control of key metabolic enzymes makes this kinase a central player in glucose and lipid homeostasis. Recently, by screening a library of synthetic small molecules selected for their structural similarity with the natural polyphenol resveratrol, we identified RSVA314 and RSVA405 as potent indirect activators of AMPK (half-maximal effective concentration (EC50) = 1 µmol/L in cell-based assays). Here we show that RSVA314 and RSVA405 can significantly activate AMPK and inhibit acetyl-CoA carboxylase (ACC), one target of AMPK and a key regulator of fatty acid biogenesis, in nondifferentiated and proliferating 3T3-L1 adipocytes. We found that RSVA314 and RSVA405 treatments inhibited 3T3-L1 adipocyte differentiation by interfering with mitotic clonal expansion during preadipocyte proliferation (halfmaximal inhibitory concentration (IC50) = 0.5 µmol/L). RSVA314 and RSVA405 prevented the adipogenesis-dependent transcriptional changes of multiple gene products involved in the adipogenic process, including peroxisome proliferator-activated receptor (PPAR)-γ, CCAAT/enhancer-binding protein α (C/EBPα), fatty acid synthase, fatty acid binding protein 4 (aP2), RANTES or resistin. Furthermore, orally administered RSVA405 at 20 and 100 mg/kg/d significantly reduced the body weight gain of mice fed a high-fat diet. This work shows that the novel small-molecule activators of AMPK (RSVA314 and RSVA405) are potent inhibitors of adipogenesis and thus may have therapeutic potential against obesity.
74 citations
TL;DR: In this paper, a review examines cholesterol asymmetry in SPM, potential mechanisms of regulation and impact on membrane structure and function, and several potential candidates have been proposed as mechanisms involved in regulation of SPM cholesterol imbalance: apoE, low-density lipoprotein receptor, sterol carrier protein-2, fatty acid binding proteins, polyunsaturated fatty acids, P-glycoprotein and caveolin-1.
Abstract: Lipids are essential for the structural and functional integrity of membranes. Membrane lipids are not randomly distributed but are localized in different domains. A common characteristic of these membrane domains is their association with cholesterol. Lipid rafts and caveolae are examples of cholesterol enriched domains, which have attracted keen interest. However, two other important cholesterol domains are the exofacial and cytofacial leaflets of the plasma membrane. The two leaflets that make up the bilayer differ in their fluidity, electrical charge, lipid distribution, and active sites of certain proteins. The synaptic plasma membrane (SPM) cytofacial leaflet contains over 85% of the total SPM cholesterol as compared with the exofacial leaflet. This asymmetric distribution of cholesterol is not fixed or immobile but can be modified by different conditions in vivo: (i) chronic ethanol consumption; (ii) statins; (iii) aging; and (iv) apoE isoform. Several potential candidates have been proposed as mechanisms involved in regulation of SPM cholesterol asymmetry: apoE, low-density lipoprotein receptor, sterol carrier protein-2, fatty acid binding proteins, polyunsaturated fatty acids, P-glycoprotein and caveolin-1. This review examines cholesterol asymmetry in SPM, potential mechanisms of regulation and impact on membrane structure and function.
66 citations
TL;DR: The metabolic changes observed in both null models appear to occur by nontranscriptional mechanisms, supporting the hypothesis that the enterocyte FABPs are specifically trafficking their ligands to their respective metabolic fates.
Abstract: It has long been known that mammalian enterocytes coexpress two members of the fatty acid-binding protein (FABP) family, the intestinal FABP (IFABP) and the liver FABP (LFABP). Both bind long-chain fatty acids and have similar though not identical distributions in the intestinal tract. While a number of in vitro properties suggest the potential for different functions, the underlying reasons for expression of both proteins in the same cells are not known. Utilizing mice genetically lacking either IFABP or LFABP, we directly demonstrate that each of the enterocyte FABPs participates in specific pathways of intestinal lipid metabolism. In particular, LFABP appears to target fatty acids toward oxidative pathways and dietary monoacylglycerols toward anabolic pathways, while IFABP targets dietary fatty acids toward triacylglycerol synthesis. The two FABP-null models also displayed differences in whole body response to fasting, with LFABP-null animals losing less fat-free mass and IFABP-null animals losing more fat mass relative to wild-type mice. The metabolic changes observed in both null models appear to occur by nontranscriptional mechanisms, supporting the hypothesis that the enterocyte FABPs are specifically trafficking their ligands to their respective metabolic fates.
TL;DR: These findings will bring new insight into the fat-related carcass traits of beef cattle and will thus contribute to the beef industry.
Abstract: The fatty acid composition of adipose tissue in beef has been recognized as an important trait because of its relationship with beef quality, including favorable beef flavor and tenderness. Over the last decade, we have tried to identify the genes responsible for the fatty acid composition in cattle, and have found the following. (i) Genetic polymorphism of stearoyl-CoA desaturase (SCD) is one of the responsible genes associated with fatty acid composition. The average effects of gene substitution of the SCD type A gene on the monounsaturated fatty acid (MUFA) percentage and the melting point of intramuscular fat were approximately +1.0% and -1.0°C, respectively. (ii) Intron polymorphism of sterol regulatory element binding protein-1 (SREBP-1) also affected MUFA. (iii) No effect of SCD or SREBP-1 genotypes on any representative carcass traits of Japanese Black in the field population was observed. (iv) Additional genetic markers adipocytes fatty acid binding protein 4 (FABP4) and liver X receptor α also affected the fatty acid composition. (v) SCD and FABP4 significantly affected fatty acid composition in Holstein steers. These findings will bring new insight into the fat-related carcass traits of beef cattle and will thus contribute to the beef industry.
TL;DR: The expression of FABP 3, 5, and 7 in the SGZ supports a role of astrocyte‐ and/or neural progenitor‐derived FABPs as components of the molecular machine regulating the progenitors cell niche in the adult primate brain.
Abstract: Intracellular fatty acid (FA) chaperones known as FA-binding proteins (FABPs) are a group of molecules known to participate in cellular metabolic processes such as lipid storage, membrane synthesis, and β-oxidation or to coordinate transcriptional programs. However, their role in adult neurogenesis still remains obscure. The FABPs expressed in the central nervous system (CNS) are heart-type (FABP3), epidermal-type (FABP5), and brain-type (FABP7). These three FABPs possess a differential affinity for polyunsaturated fatty acids (PUFAs). Recently, we reported that GPR40, a receptor for free FAs and particularly for PUFAs, is expressed in the CNS of adult monkeys and upregulated after transient global brain ischemia in the hippocampal subgranular zone (SGZ), a neurogenic niche in adulthood. The SGZ showed a peak proliferation of progenitor cells and maximal expression of GPR40 during the second week after ischemia. As both FABPs and GPR40 might be closely related to the adult neurogenesis, here, we studied the expression of FABP 3, 5, and 7 in the SGZ, comparing normal and postischemic adult monkeys. Immunoblotting revealed that FABP5 and FABP7, but not FABP3, were significantly increased on day 15 after ischemia when compared with the nonischemic control. Immunohistochemistry showed that FABP5 was almost undetectable in the control SGZ but was abundant on day 15 after ischemia. FABP 3, 5, and 7 were expressed in S-100β-positive astrocytes and nestin-positive neural progenitors. However, only FABP 5 and 7 were found in bromodeoxyuridine (BrdU)-positive newly generated cells. FABPs were most frequently coexpressed with the S-100β-positive astrocytes, whereas βIII-tubulin-or polysialylated neural cell-adhesion molecule (PSA-NCAM)-positive newborn neurons in the vicinity of the astrocytes expressed none of the three FABPs. These results support a role of astrocyte- and/or neural progenitor-derived FABPs as components of the molecular machine regulating the progenitor cell niche in the adult primate brain.
TL;DR: This work crystallized human liver fatty acid-binding protein in apo, holo, and intermediate states of palmitic acid engagement to support a heads-in mechanism for ligand entry within LFABP, which undergoes structural remodeling.
TL;DR: The results suggest that genotypes of SCD and FABP4 may in part affect meat quality in Holstein and that SCD genotype possibly had effect on composition of C18:1 and monounsaturated fatty acid.
Abstract: Fatty acid composition of adipose tissue has been recognized as an important carcass trait because of its relationship with eating quality such as favorable beef flavor and tenderness. Therefore, we investigated the effects of genetic polymorphisms of liver X receptor, alpha (LXR), stearoyl-CoA desaturase (SCD), Fatty acid synthase (FASN), and Fatty acid binding protein 4 (FABP4) on fatty acid composition in intramuscular fat tissue of Holstein steers. The major allele frequencies were 0.705 in SCD, 0.518 in FABP4, 0.888 in FASN, and 0.984 in LXR. Genotyping of SCD showed significant effect on C14:0, C14:1, C18:0 and saturated fatty acid (P < 0.05). In addition, the result suggested that SCD genotype possibly had effect on composition of C18:1 and monounsaturated fatty acid. Genotype of FABP4 had significant effect on composition of C16:0. Effect of LXR genotypes could not be analyze because of extremely biased genotype frequencies. Our results suggest that genotypes of SCD and FABP4 may in part affect meat quality in Holstein.
TL;DR: In conclusion, coordinated downregulation of sequential steps involved in fatty acid and oxidative metabolism occur in the human heart, accompanied by upregulation of the glucose transporters.
Abstract: In the hypertrophied human heart, fatty acid metabolism is decreased and glucose utilisation is increased. We hypothesized that the sarcolemmal and mitochondrial proteins involved in these key metabolic pathways would mirror these changes, providing a mechanism to account for the modified metabolic flux measured in the human heart. Echocardiography was performed to assess in vivo hypertrophy and aortic valve impairment in patients with aortic stenosis (n = 18). Cardiac biopsies were obtained during valve replacement surgery, and used for western blotting to measure metabolic protein levels. Protein levels of the predominant fatty acid transporter, fatty acid translocase (FAT/CD36) correlated negatively with levels of the glucose transporters, GLUT1 and GLUT4. The decrease in FAT/CD36 was accompanied by decreases in the fatty acid binding proteins, FABPpm and H-FABP, the β-oxidation protein medium chain acyl-coenzyme A dehydrogenase, the Krebs cycle protein α-ketoglutarate dehydrogenase and the oxidative phosphorylation protein ATP synthase. FAT/CD36 and complex I of the electron transport chain were downregulated, whereas the glucose transporter GLUT4 was upregulated with increasing left ventricular mass index, a measure of cardiac hypertrophy. In conclusion, coordinated downregulation of sequential steps involved in fatty acid and oxidative metabolism occur in the human heart, accompanied by upregulation of the glucose transporters. The profile of the substrate transporters and metabolic proteins mirror the metabolic shift from fatty acid to glucose utilisation that occurs in vivo in the human heart.
TL;DR: Increased plasma A-FABP in non-elderly men had a significant association with the presence of CAD, independent of established CAD risk factors.
Abstract: Background
Adipocyte fatty acid-binding protein (A-FABP) has been reported to play critical roles in the development of atherosclerosis. We investigated whether an increased in plasma A-FABP level can be independently associated with the presence of coronary artery disease (CAD).
TL;DR: FFA influx in cardiac myocytes is mediated by a membrane pump whose transport rate constants may be modulated by FAT/CD36, and it is concluded that rates of FFA transport and etomoxir-sensitive metabolism are regulated independently.
TL;DR: Three flavonoids concentration-dependently enhanced the accumulation of triglyceride, a marker of adipogenesis, and tetramethylkaempferol and pentamethylquercetin significantly increased the amount of adiponectin released into the medium and the uptake of 2-deoxyglucose into the cells.
TL;DR: Evidence is provided that in obese animals more fat accumulates within the heart as a result of their increased transport across the membranes of heart cells, not due to reductions in mitochondrial number or function.
Abstract: We aimed to determine whether an increased rate of long-chain fatty acid (LCFA) transport and/or a reduction in mitochondrial oxidation contributes to lipid deposition in hearts, as lipid accumulation within cardiac muscle has been associated with heart failure. In hearts of lean and obese Zucker rats we examined: (a) triacylglycerol (TAG) and mitochondrial content and distribution using transmission electron microscopy (TEM), (b) LCFA oxidation in cardiac myocytes, and in isolated subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria, and (c) rates of LCFA transport into cardiac vesicles. Compared to lean rats, in obese Zucker rats, lipid droplet size was similar but there were more (P 0.05). In contrast, sarcolemmal plasma membrane fatty acid binding protein (FABPpm) and fatty acid translocase (FAT/CD36) protein and palmitate transport rates into cardiac vesicles were increased (P < 0.05; +50%) in obese animals. Collectively these data indicate that mitochondrial dysfunction in LCFA oxidation is not responsible for lipid accumulation in obese Zucker rat hearts. Rather, increased sarcolemmal LCFA transport proteins and rates of LCFA transport result in a greater number of lipid droplets within cardiac muscle.
TL;DR: This review article summarizes the findings on the pathophysiological roles and dynamics of renal human L‐FABP in the recent experimental studies performed using this Tg mouse model.
Abstract: :
Kidney disease develops to renal failure over a period of days, months or years, hence, clinical markers that indicate the real-time renal pathophysiological conditions is important. Liver type fatty acid binding protein (L-FABP) is a 14 kDa molecule predominantly expressed in human proximal tubules. Clinical studies demonstrate that urinary excretion of L-FABP derived from the proximal tubules is an excellent biomarker for predicting and monitoring deterioration of renal function or for early detection of kidney disease. However, in order to clarify the pathophysiological roles or dynamics of renal L-FABP in diseased settings, in vivo experimental studies of kidney diseases are indispensable. Since L-FABP is not endogenously expressed in murine kidneys, a transgenic (Tg) mouse model with expression of the human L-FABP gene was established. This review article summarizes the findings on the pathophysiological roles and dynamics of renal human L-FABP in the recent experimental studies performed using this Tg mouse model.
TL;DR: The aim of this work was to present current data on the clinical significance of fatty acid binding proteins.
Abstract: Excessive levels of free fatty acids are toxic to cells. The human body has evolved a defense mechanism in the form of small cytoplasmic proteins called fatty acid binding proteins (FABPs) that bind long-chain fatty acids (LCFA), and then refer them to appropriate intracellular disposal sites (oxidation in mitochondria and peroxisomes or storage in the endoplasmic reticulum). So far, nine types of these proteins have been described, and their name refers to the place in which they were first identified or where they can be found in the greatest concentration. The most important FABPs were isolated from the liver (L-FABP), heart (H-FABP), intestine (I-FABP), brain (B-FABP), epidermis (E-FABP) and adipocytes (A-FABP). Determination of H-FABP is used in the diagnosis of myocardial infarction, and L-FABP in kidney lesions of different etiologies. It is postulated that FABPs play an important role in the pathogenesis of metabolic diseases. Elevated levels of A-FABP have been found in the pericardial fat tissue and were associated with cardiac dysfunction in obese people. A rise in A-FABP has been observed in patients with type II diabetes. I-FABP is known as a marker of cell damage in the small intestine. Increased concentration of B-FABP has been associated with human brain tumors such as glioblastoma and astrocytoma, as well as with neurodegenerative diseases (Alzheimer's, Parkinson's) and other disorders of cognitive function. The aim of this work was to present current data on the clinical significance of fatty acid binding proteins.
TL;DR: The authors would like to introduce a PUFA-GPR40 signaling pathway that is specific for the primate brain, considering the role of GPR40 and FABP in the hippocampal neurogenic niche.
TL;DR: It is demonstrated here that, besides their apparently opposite ligand transfer mechanisms, both LFABP and IFABP are able to interact with phospholipid membranes, but the factors that modulate such interactions are different for each protein, further implying different roles for IFABp and LFABp in the intracellular context.
TL;DR: The identification of a potential biomarker for acute in vivo FABP4 inhibition that is applicable for further investigations and can be implemented in simple and fast-flow injection mass spectrometry assays is reported.
Abstract: The fatty acid binding protein 4 (FABP4) belongs to the family of lipid chaperones that control intracellular fluxes and compartmentalization of their respective ligands (e.g., fatty acids). FABP4, which is almost exclusively expressed in adipocytes and macrophages, contributes to the development of insulin resistance and atherosclerosis in mice. Lack of FABP4 protects against the development of insulin resistance associated with genetic or diet-induced obesity in mice. Furthermore, total or macrophage-specific FABP4 deficiency is protective against atherosclerosis in apolipoprotein E-deficient mice. The FABP4 small-molecule inhibitor BMS309403 has demonstrated efficacy in mouse models for type 2 diabetes mellitus and atherosclerosis, resembling phenotypes of mice with FABP4 deficiency. However, despite the therapeutically attractive long-term effects of FABP4 inhibition, an acute biomarker for drug action is lacking. The authors applied mass spectrometry lipidomics analysis to in vitro and in vivo (plasma and adipose tissue) samples upon inhibitor treatment. They report the identification of a potential biomarker for acute in vivo FABP4 inhibition that is applicable for further investigations and can be implemented in simple and fast-flow injection mass spectrometry assays. In addition, this approach can be considered a proof-of-principle study that can be applied to other lipid-pathway targeting mechanisms.
TL;DR: Overall, Atlantic salmon FA transporters are regulated by fasting and insulin on in vivo and in vitro models.
Abstract: We have examined the nutritional and insulin regulation of the mRNA expression of transmembrane fatty acid (FA) transporters [FA transport protein-1 (FATP1) and CD36] together with the lipoprotein lipase (LPL), the cytosolic FA carrier FA binding protein (FABP3), and mitochondrial FA-CoA and -carnitine palmitoyl transferase carriers (CPT)1 and -2 in Atlantic salmon tissues and myocyte cell culture. Two weeks of fasting diminished FATP1, CD36, and LPL in adipose tissue, suggesting a reduction in FA uptake, while FABP3 increased in liver, probably enhancing the transport of FA to the mitochondria. Insulin injection decreased FATP1 and CD36 in white and red muscles, while both transporters were upregulated in the adipose tissue in agreement with the role of insulin-inhibiting muscle FA oxidation and stimulating adipose fat stores. Serum deprivation of 48 h in Atlantic salmon myotubes increased FATP1, FABP3, and CPT-2, while CPT-1 was diminished. In myotubes, insulin induced FATP1 expression but decreased CD36, FABP3, and LPL, suggesting that FATP1 could be more involved in the insulin-stimulated FA uptake. Insulin increased the FA uptake in myotubes mediated, at least in part, through the relocation of FATP1 protein to the plasma membrane. Overall, Atlantic salmon FA transporters are regulated by fasting and insulin on in vivo and in vitro models.
TL;DR: This study is the first to report on two potential target proteins of rosiglitazone, such as adenomatosis polyposis coli 2 (APC2), and eukaryotic translation initiation factor 5A-1 (eIF5A) related to apoptosis and cell division related to cell division.
Abstract: Rosiglitazone, one of the thiazolidinedione (TZD), is an oral antidiabetic drug that activates a gamma isoform of peroxisome proliferator-activated receptor (PPARγ). To identify target proteins induced by rosiglitazone in adipocytes, we first performed simultaneous in-depth proteomic profiling of cytosolic proteins and secreted proteins (secretome) from 3T3-L1 adipocytes using a label-free quantification method with nano-UPLC MS/MS. In total, we identified 646 proteins from 3T3-L1 adipocytes, of which 172 and 162 proteins were upregulated and downregulated >1.5-fold, respectively, in rosiglitazone-treated cells, as compared to controls. Some differentially expressed proteins in particular, including fatty acid translocase (FAT)/CD36, fatty acid binding protein, lipoprotein lipase, acetyl CoA acyltransferase, carnitine O-palmitoyltransferase 2, sterol carrier protein, adiponectin, and phosphoenolpyruvate carboxykinase could explain the current action mechanism of TZDs. Furthermore, this study is the first to report on two potential target proteins of rosiglitazone, such as adenomatosis polyposis coli 2 (APC2), and eukaryotic translation initiation factor 5A-1 (eIF5A) related to apoptosis and cell division. Our data clearly suggest that in-depth proteomic approaches using cytosolic and secreted proteins are important and necessary for identification of drug targets at the protein level.
TL;DR: The present experimental model suggests that tubular enhancement of L-FABP may protect mice with anti-GBM GN from progression of both tubulointerstitial and glomerular injury.
Abstract: Background. In glomerulonephritis (GN), an overload of free fatty acids (FFA) bound to albumin in urinary protein may induce oxidative stress in the proximal tubules. Human liver-type fatty acid-binding protein (hL-FABP) expressed in human proximal tubules, but not rodents, participates in intracellular FFA metabolism and exerts anti-oxidative effects on the progression of tubulointerstitial damage. We examined whether tubular enhancement of this anti-oxidative action modulates the progression of glomerular damage in immune-mediated GN in hL-FABP chromosomal gene transgenic (Tg) mice.
Methods. Anti-glomerular basement membrane antibody-induced glomerulonephritis (anti-GBM GN) was induced in Tg and wild-type mice (WT). Proteinuria, histopathology, polymorphonuclear (PMN) influx, expression of tubulointerstitial markers for oxidative stress 4-hydroxy-2-Nonenal (HNE) and fibrosis (α-smooth muscle actin), proximal tubular damage (Kim-1), Peroxisome Proliferator-Activated Receptor γ (PPAR γ) and inflammatory cytokines [Monocyte Chemotactic Protein-1, tumor necrosis factor-alpha (TNF-α) and Transforming growth factor beta (TGF-β)] were analyzed. The mice were also treated with an angiotensin type II receptor blocker (ARB).
Results. The urinary protein level in Tg mice decreased significantly during the acute phase (∼Day 5). Tg mice survived for a significantly longer time than WT mice, with an attenuation of tubulointerstitial damage score and expression of each tubulointerstitial damage marker observed at Day 7. Expression of inflammatory cytokines on Day 7 was higher in WT mice than Tg mice and correlated strongly with PPARγ expression in WT mice, but not in Tg mice. Interestingly, Tg mice showed insufficient PMN influx at 3 and 6 h, with simultaneous elevation of urinary L-FABP and reduction in HNE expression. The two strains of mice showed different types of glomerular damage, with mild mesangial proliferation in Tg mice and severe endothelial swelling with vascular thrombosis in WT mice. The glomerular damage in Tg mice was improved by administration of an ARB.
Conclusions. The present experimental model suggests that tubular enhancement of L-FABP may protect mice with anti-GBM GN from progression of both tubulointerstitial and glomerular injury.
TL;DR: Aberrant protein levels from several pathways in fetal DS are challenging as well as fertilizing the area of research and providing the basis for additional neurochemical and functional studies.
TL;DR: The results indicate that patients with pre-diabetic patients are at increased risk for cardiovascular disease and serum H-FABP levels could represent a useful marker for myocardial performance in patients with IFG and IGT.
Abstract: Background
Heart type fatty acid binding protein (H-FABP) has been closely associated with acute coronary syndrome, cardiac abnormalities, stroke, and obstructive sleep disorder in previous studies. The aim of this study was to evaluate and compare the serum H-FABP levels and carotid artery intima-media thickness (CIMT) between patients with prediabetes and control subjects.