Adipocyte Fatty Acid-binding Protein Research Articles

Novel anti-adipogenic activity of anti-malarial amodiaquine through suppression of PPARγ activity.

Amodiaquine (AQ) was developed as a selective drug against Plasmodium falciparum malaria infection and has received increasing attention as a therapeutic agent for the treatment of rheumatoid arthritis, Parkinson's disease, and cancer due to its anti-inflammatory, anti-proliferative, and autophagic-lysosomal blockade properties. As autophagy activation is involved in promoting adipogenic differentiation, we examined whether anti-autophagic AQ affected adipocyte differentiation of 3T3-L1 pre-adipocytes. AQ dose-dependently and significantly suppressed adipocyte differentiation in conjunction with decreases in lipid droplet formation and expression of adipogenic markers including adiponectin, adipocyte fatty acid-binding protein 2 (aP2), resistin, and leptin. Although peroxisome proliferator-activated receptor γ (PPARγ) decreases by inhibition of autophagy, AQ treatment did not induce PPARγ degradation despite the suppression of autophagolysosomal degradation. Instead, AQ suppressed the PPARγ activity to transcriptionally activate the aP2 gene transcription through the selective prevention of nuclear localization of PPARγ. These results demonstrated the novel anti-adipogenic activity of AQ and identified its underlying mechanism that AQ suppressed adipogenic gene expression and lipid formation by inhibiting nuclear localization of PPARγ in an autophagy-independent manner. AQ is recommended as a safe and effective anti-obesity drug for controlling overweight and obesity.

Circulating adipocyte fatty acid-binding protein is a predictor of cardiovascular events in patients with stable angina undergoing percutaneous coronary intervention

BackgroundAdipocyte fatty acid-binding protein (A-FABP) is expressed in both adipocytes and macrophages. Recent studies have shown that A-FABP is secreted by adipocytes and that the A-FABP concentration is associated with obesity, insulin resistance, and atherosclerosis. We have reported that the coronary atherosclerotic burden is associated with the serum A-FABP concentration. In the present study, we investigated whether the serum A-FABP concentration is associated with prognosis in patients with stable angina pectoris who have undergone percutaneous coronary intervention (PCI).MethodsThis was a prospective single-center trial. In total, 130 patients with stable angina pectoris undergoing their first PCI were enrolled from August 2008 to July 2010 at Kagawa Prefectural Central Hospital. The primary endpoints were cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, revascularization, and hospitalization for heart failure.ResultsDuring the follow-up (median, 50 months; interquartile range, 23–66 months), 49 cardiovascular events occurred. Kaplan–Meier analysis showed that the cumulative incidence of the primary endpoints in the high A-FABP group (median A-FABP concentration of ≥ 18.6 ng/ml) was greater than that in the low A-FABP group. Cox analysis showed that the A-FABP concentration was an independent predictor of cardiovascular events adjusted for age and the presence of multi-vessel disease (hazard ratio, 1.03; 95% confidence interval, 1.01–1.04; p = 0.01).ConclusionThe serum A-FABP concentration is associated with prognosis in patients with stable angina undergoing PCI, suggesting that the serum A-FABP concentration could be useful for risk assessment of secondary prevention.Trial registrationUMIN Clinical Trials Registry UMIN000029283 (registration date: September 25, 2017), retrospectively registered.

Suppression of adipocyte differentiation and lipid accumulation by stearidonic acid (SDA) in 3T3-L1 cells

BackgroundIncreased consumption of omega-3 (ω-3) fatty acids found in cold-water fish and fish oil has been reported to protect against obesity. A potential mechanism may be through reduction in adipocyte differentiation. Stearidonic acid (SDA), a plant-based ω-3 fatty acid, has been targeted as a potential surrogate for fish-based fatty acids; however, its role in adipocyte differentiation is unknown. This study was designed to evaluate the effects of SDA on adipocyte differentiation in 3T3-L1 cells.Methods3T3-L1 preadipocytes were differentiated in the presence of SDA or vehicle-control. Cell viability assay was conducted to determine potential toxicity of SDA. Lipid accumulation was measured by Oil Red O staining and triglyceride (TG) quantification in differentiated 3T3-L1 adipocytes. Adipocyte differentiation was evaluated by adipogenic transcription factors and lipid accumulation gene expression by quantitative real-time polymerase chain reaction (qRT-PCR). Fatty acid analysis was conducted by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS).Results3T3-L1 cells treated with SDA were viable at concentrations used for all studies. SDA treatment reduced lipid accumulation in 3T3-L1 adipocytes. This anti-adipogenic effect by SDA was a result of down-regulation of mRNA levels of the adipogenic transcription factors CCAAT/enhancer-binding proteins alpha and beta (C/EBPα, C/EBPβ), peroxisome proliferator-activated receptor gamma (PPARγ), and sterol-regulatory element binding protein-1c (SREBP-1c). SDA treatment resulted in decreased expression of the lipid accumulation genes adipocyte fatty-acid binding protein (AP2), fatty acid synthase (FAS), stearoyl-CoA desaturase (SCD-1), lipoprotein lipase (LPL), glucose transporter 4 (GLUT4) and phosphoenolpyruvate carboxykinase (PEPCK). The transcriptional activity of PPARγ was found to be decreased with SDA treatment. SDA treatment led to significant EPA enrichment in 3T3-L1 adipocytes compared to vehicle-control.ConclusionThese results demonstrated that SDA can suppress adipocyte differentiation and lipid accumulation in 3T3-L1 cells through down-regulation of adipogenic transcription factors and genes associated with lipid accumulation. This study suggests the use of SDA as a dietary treatment for obesity.

Anti-Obesity Activity of Saringosterol Isolated from Sargassum muticum (Yendo) Fensholt Extract in 3T3-L1 Cells.

Saringosterol, a steroid isolated from Sargassum muticum, a brown edible alga widely distributed on the seashores of southern and eastern Korea, has been shown to exhibit anti-obesity effect. In this study, we investigated the anti-obesity activity of saringosterol through various experiments. The inhibitory effect of saringosterol on adipogenesis was evaluated via Oil Red O staining in 3T3-L1 preadipocytes. After confirming that saringosterol is not cytotoxic to these cells by using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, the effect of saringosterol on the expression of various adipogenesis-related genes was analyzed via quantitative real-time polymerase chain reaction and western blotting. We demonstrated that saringosterol dose dependently inhibited adipocyte differentiation and expression of adipogenic marker genes such as adipocyte fatty acid-binding protein, adiponectin, resistin, and fatty acid synthase in 3T3-L1 cells. In addition, saringosterol significantly inhibited the mRNA and protein expression of peroxisome proliferator-activated receptor γ and CCAAT enhancer-binding protein α in 3T3-L1 cells. Collectively, these findings indicate that saringosterol isolated from S. muticum exhibits anti-obesity effect by inhibiting the expression of adipogenic transcription factors and marker genes and that it may be developed as a drug to suppress adipogenesis. Copyright © 2017 John Wiley & Sons, Ltd.

High serum adipocyte fatty acid binding protein level as a potential biomarker of aortic arterial stiffness in hypertensive patients with metabolic syndrome

BackgroundThe adipocyte-fatty-acid-binding protein (A-FABP) has been implicated in arterial stiffness, metabolic syndrome (MetS), and cardiovascular disease. We aimed to determine the relationship among serum A-FABP concentration, cardiometabolic risk factors, and central arterial stiffness in a hypertensive population. MethodsFasting blood samples and baseline characteristics were obtained from 110 hypertensive patients. Serum A-FABP concentrations were determined by enzyme immunoassay kit. High arterial stiffness was defined as carotid-femoral pulse wave velocity values >10m/s via the SphygmoCor system. ResultsPatients with MetS and high arterial stiffness accounted for 67.3% and 42.7% of the study population, respectively. Serum A-FABP was positively associated with MetS and high arterial stiffness (P=0.006 and P<0.001, respectively). Multivariable stepwise linear regression analysis of the significant variables of arterial stiffness revealed that logarithmically transformed A-FABP (log-A-FABP, β=0.278, P=0.002) was positively correlated arterial stiffness in hypertensive patients. Subgroup analysis revealed that log-A-FABP (β=0.327, P=0.003), age (β=0229, P=0.032), and triglyceride (β=0.307, P=0.004) were significantly positively correlated with arterial stiffness in hypertensive patients with MetS. ConclusionsElevated A-FABP concentration could be a predictor for MetS and arterial stiffness in hypertensive patients.

Adipocyte fatty acid-binding protein: A predictive marker of metabolic syndrome

Adipocyte fatty acid-binding protein: A predictive marker of metabolic syndrome

Proteomics Analysis Reveals an Important Role for the PPAR Signaling Pathway in DBDCT-Induced Hepatotoxicity Mechanisms.

A patented organotin di-n-butyl-di-(4-chlorobenzohydroxamato)tin (DBDCT) with high a antitumor activity was designed, however, its antitumor and toxic mechanisms have not yet been clearly illustrated. Hepatic proteins of DBDCT-treated rats were identified and analyzed using LC-MS/MS with label-free quantitative technology. In total, 149 differentially expressed proteins were successfully identified. Five protein and mRNA expressions were involved in the peroxisome proliferator-activated receptor (PPAR) signaling pathway, including a scavenger receptor (CD36), adipocyte fatty acid binding protein 4 (FABP4), enoyl-CoA hydratase (EHHADH), acetyl-CoA acyltransferase 1 (ACAA1), and phosphoenolpyruvate carboxykinase (PEPCK) in DBDCT-treated Rat Liver (BRL) cells. PPAR-α and PPAR-λ were also significantly decreased at both protein and mRNA levels. Furthermore, compared with the DBDCT treatment group, a special blocking agent of PPAR-λ T0070907 was used to evaluate the relationship between PPAR-λ and its downstream genes. Our studies indicated that DBDCT may serve as a modulator of PPAR-λ, further up-regulating CD36, FABP4 and EHHADH on the PPAR signal pathway.

Fatty acid binding protein 4/aP2-dependent BLT1R expression and signaling

Previous studies have shown that reduced levels of the adipocyte fatty acid binding protein (FABP)4 (AFABP/aP2), result in metabolic improvement including potentiated insulin sensitivity and attenuated atherosclerosis. Mechanistically, pharmacologic or genetic inhibition of FABP4 in macrophages upregulates UCP2, attenuates reactive oxygen species (ROS) production, polarizes cells toward the anti-inflammatory M2 state, and reduces leukotriene (LT) secretion. At the protein level, FABP4 stabilizes LTA4 toward chemical hydrolysis, thereby potentiating inflammatory LTC4 synthesis. Herein, we extend the FABP4-LT axis and demonstrate that genetic knockout of FABP4 reduces expression of the major macrophage LT receptor, LTB4 receptor 1 (BLT1R), via a ROS-dependent mechanism. Consistent with inflammation driving BLT1R expression, M1 polarized macrophages express increased levels of BLT1R relative to M2 polarized macrophages and treatment with proinflammatory lipopolysaccharide increased BLT1R mRNA and protein expression. In FABP4 knockout macrophages, silencing of UCP2, increased ROS levels and led to increased expression of BLT1R mRNA. Similarly, addition of exogenous H2O2 upregulated BLT1R expression, whereas the addition of a ROS scavenger, N-acetyl cysteine, decreased BLT1R levels. As compared with WT macrophages, LTB4-BLT1R-dependent JAK2-phosphorylation was reduced in FABP4 knockout macrophages. In summary, these results indicate that FABP4 regulates the expression of BLT1R and its downstream signaling via control of oxidative stress in macrophages.

Serum adipocyte fatty acid-binding protein level is associated with arterial stiffness quantified with cardio-ankle vascular index in kidney transplant patients

Arterial stiffness is an established marker of cardiovascular risk and an independent predictor of cardiovascular disease (CVD) events and mortality in kidney transplant (KT) patients. Adipocyte fatty acid-binding protein (A-FABP), a novel adipokine, is positively associated with atherosclerosis. The present study evaluated the relationship between fasting circulating A-FABP and peripheral arterial stiffness using the cardio-ankle vascular index (CAVI) in KT patients. Fasting blood samples were collected from 74 KT patients, and serum A-FABP levels were measured using an enzyme immunoassay. CAVI was calculated using a waveform device (CAVI-VaSera VS-1000). The cutoff values for high and low levels of arterial stiffness were defined by the CAVI values of ≥9 and <9, respectively. Thirty-four patients (45.9%) were classified into the high arterial stiffness group. Compared with the low arterial stiffness group, the high arterial stiffness group had higher values for age (p=0.015), systolic blood pressure (p<0.001), pulse pressure (p<0.001), duration of kidney transplantation (p=0.005), serum total cholesterol and triglyceride levels (p=0.033 and 0.047, respectively), glomerular filtration rate (p=0.019), fasting glucose levels (p=0.012), and serum A-FABP levels (p<0.001). Multivariate forward stepwise linear regression analysis showed that age (p=0.004), systolic blood pressure (p=0.001), and serum A-FABP levels (p=0.003) were independent predictors of CAVI value in KT patients. Serum fasting A-FABP level is positively associated with peripheral arterial stiffness in KT patients.

Annual Wormwood Leaf Inhibits the Adipogenesis of 3T3-L1 and Obesity in High-Fat Diet-Induced Obese Rats.

Annual wormwood (AW) (Artemisia annua L.) has anti-malarial, anti-bacterial, anti-oxidant, anti-tumour, and anti-inflammatory activities. In the present study, we evaluated the effects of annual wormwood leaves (AWL) on adipocyte differentiation in 3T3-L1 cells and high-fat diet (HFD)-induced obese rats. 3T3-L1 adipocytes and HFD-induced obese rats were treated with AWL, and its effect on gene expression was analyzed using RT-PCR and Western blotting experiments. Treatment with AWL effectively prevented triglyceride accumulation during adipogenesis in a dose-dependent manner. Consistently, AWL suppressed the differentiation of 3T3-L1 preadipocytes into adipocytes through the downregulation of dexamethasone, 3-isobutyl-1- methylxanthine, and insulin (DMI)-induced serine/threonine kinase protein kinase B (PKB/Akt) activation and the expression of adipogenic genes, including the CCAAT/enhancer binding protein-α (C/EBPα) and peroximal proliferator-activated receptor-γ (PPARγ). Moreover, the expression of adipocyte fatty acid-binding protein 4 (aP2), which is a known PPARγ-target gene, was downregulated by AWL treatment. Oral administration of AWL extracts significantly decreased the body weight gain, adipose tissue mass, adipocyte cell size, serum triglyceride (TG), and total cholesterol (TC) levels in HFD-induced obese rats. These results provide novel insight into the molecular mechanisms underlying the anti-obesity effects of AWL that are mediated by the downregulation of the expression of major adipogenic transcription factors, C/EBPα and PPARγ and Akt signalling.

Possitive correlation between adipocyte fatty acid-binding protein and epicardial fat in patients with a family history of cardiovascular disesase.

Adipocyte fatty acid-binding protein (A-FABP) is a promising link between metabolic syndrome and atherosclerosis. Epicardial fat (EPI) is an independent risk factor for cardiovascular disease (CVD). The aim of this pilot study was to evaluate the correlation between EPI and A-FABP in asymptomatic patients with a family history of CVD. 59 subjects (39 males) (median = 54 years old) were enrolled in the study and their EPI thickness and A-FABP levels were assessed. EPI was found in 46 patients (77.9%). There were positive correlations between EPI and A-FABP (r=0.336; P=0.010), age (r=0.526; P<0.001), fibrinogen (r=0.304; P=0.023) and systolic blood pressure (r=0.279; P=0.034). A positive correlation was found between EPI and A-FABP in a subgroup of overweight and obese patients (0.389; P=0.041, 0.407; P=0.004) and in the subgroup of patients with excluded CVD (r=0.368; P=0.006). We found a positive correlation between EPI and A-FABP in a group of patients with a family history of CVD and in subgroups of overweight and obese patients.

Adipocyte Fatty-Acid Binding Protein is Overexpressed in Cirrhosis and Correlates with Clinical Outcomes

Fatty-acid-binding proteins (FABPs) are small intracellular proteins that coordinate lipid-mediated processes by targeting metabolic and immune response pathways. The aim of the study was to investigate plasma FABPs levels and their relationship with clinical outcomes in cirrhosis. Plasma levels of L-FABP1(liver and kidney), I-FABP2(intestine), and A-FABP4(adipocyte and macrophages) were measured in 274 patients with decompensated cirrhosis. Hepatic gene expression of FABPs was assessed in liver biopsies from patients with decompensated cirrhosis and in liver cell types from mice with cirrhosis. Immunohistochemistry of A-FABP4 in human liver biopsy was also performed. Plasma levels of FABPs were increased in patients with decompensated cirrhosis compared to those of healthy subjects (L-FABP1: 25 (17–39) vs 10 (9–17) ng/mL p = 0.001, I-FABP2: 1.1 (0.5–2.1) vs 0.6 (0.4–1) ng/mL p = 0.04 and A-FABP4: 37 (20–68) vs 16 (11–33) ng/mL p = 0.002), respectively. Increased A-FABP4 levels were associated with complications of cirrhosis, acute-on-chronic liver failure and poor survival. Hepatic A-FABP4 gene expression was upregulated in decompensated cirrhosis. Macrophages were the main liver cell that over-expressed A-FABP4 in experimental cirrhosis and increased A-FABP4 was found in macrophages of human biopsies by immunohistochemistry. A-FABP4 levels are increased in decompensated cirrhosis and correlate with poor outcomes. Liver macrophages appear to be the main source of A-FABP4 in decompensated cirrhosis.

Protocols and pitfalls in obtaining fatty acid-binding proteins for biophysical studies of ligand-protein and protein-protein interactions

Adipocyte fatty acid-binding protein (AFABP: FABP4) is a member of the intracellular lipid-binding protein family that is thought to target long-chain fatty acids to nuclear receptors such as peroxisome proliferator-activated receptor gamma (PPARγ), which in turn plays roles in insulin resistance and obesity. A molecular understanding of AFABP function requires robust isolation of the protein in liganded and free forms as well as characterization of its oligomerization state(s) under physiological conditions. We report development of a protocol to optimize the production of members of this protein family in pure form, including removal of their bound lipids by mixing with hydrophobically functionalized hydroxypropyl dextran beads and validation by two-dimensional NMR spectroscopy. The formation of self-associated or covalently bonded protein dimers was evaluated critically using gel filtration chromatography, revealing conditions that promote or prevent formation of disulfide-linked homodimers. The resulting scheme provides a solid foundation for future investigations of AFABP interactions with key ligand and protein partners involved in lipid metabolism.

Tetrahydropalmatine inhibits lipid accumulation through AMPK signaling pathway in 3T3‑L1 adipocytes.

Tetrahydropalmatine (THP), one of the active components of Rhizomacorydalis, has been reported to exert several pharmacological effects, including anti‑inflammatory, anti‑tumor and analgesic activities. However, its effect on obesity and the underlying molecular mechanisms that may be involved have not yet been elucidated. In the present study, the inhibitory effects of THP on the adipogenesis in 3T3‑L1 adipocytes was examined using hstology, western blotting and RT‑qPCR. THP was identified to significantly suppress lipid accumulation in 3T3‑L1 cells and it inhibited pre‑adipocyte differentiation in a concentration‑dependent manner, as evidenced by the reduced formation of lipid droplets and decreased triglyceride levels and glycerol‑3‑phosphate dehydrogenase activity. THP downregulated the adipogenesis‑associated protein and gene expressions of sterol regulatory element‑binding protein 1, fatty acid synthase, stearoyl‑CoA desaturase 1, peroxisome proliferator activated receptor γ and CCAAT/enhancer binding protein‑α in a concentration‑dependent manner. In addition, it reduced adipocyte fatty acid binding protein and glycerol‑3‑phosphate acyltransferase gene expression in a concentration‑dependent manner. Conversely, THP increased the mRNA expression of carnitine palmitoyltransferase 1 in a concentration‑dependent manner. Furthermore, THP increased AMP‑activated protein kinase (AMPK) and acetyl‑CoA carboxylase phosphorylation in a concentration‑dependent manner. These results suggested that anti‑adipogenic activity of TPH may be mediated via the AMPK pathway in 3T3‑L1 cells.

Serum levels of nesfatin-1 are increased in gestational diabetes mellitus

Objective: To analyze the concentrations of nesfatin-1 in maternal and cord serum, to evaluate the expression of nesfatin-1 in subcutaneous adipose tissue (SAT) from pregnant women with gestational diabetes mellitus (GDM) and those with normal glucose tolerance (NGT).Methods: We studied a total of 50 GDM and 50 NGT subjects. The clinical features, serum nesfatin-1, homeostasis model assessment of insulin resistance (HOMA-IR), lipid profiles were measured at the third trimester of pregnancy. The expression of nesfatin-1 in the SAT was determined by western blot.Results: Compared with the NGT group, the GDM group showed greater levels of serum nesfatin-1, adipocyte fatty acid binding protein (AFABP), and leptin; a greater level of cord blood nesfatin-1; and a higher level of expression in SAT (p < 0.05 or p < 0.01). Fasting insulin (FI) (b = 0.317, p= 0.022) and body mass index (BMI) before delivery (b = 0.367, p=0.008) were independently associated with serum nesfatin-1. Nesfatin-1 was the independent risk factor for GDM.Conclusions: The GDM group had higher levels of maternal serum and cord blood nesfatin-1, and greater nesfatin-1 expression in SAT. Nesfatin-1 is closely related to obesity and IR in pregnancy.

(−)-Epicatechin-3-O-β-D-allopyranoside from Davallia formosana prevents diabetes and dyslipidemia in streptozotocin-induced diabetic mice

The objective of this study was to evaluate the effects and molecular mechanism of (−)-epicatechin-3-O-β-D-allopyranoside from Davallia formosana (BB) (also known as Gu-Sui-Bu) on type 1 diabetes mellitus and dyslipidemia in streptozotocin (STZ)-induced diabetic mice. This plant was demonstrated to display antioxidant activities and possess polyphenol contents. Diabetic mice were randomly divided into six groups and were given daily oral gavage doses of either BB (at three dosage levels), metformin (Metf) (at 0.3 g/kg body weight), fenofibrate (Feno) (at 0.25 g/kg body weight) or vehicle (distilled water) and a group of control (CON) mice were gavaged with vehicle over a period of 4 weeks. Treatment with BB led to reduced levels of blood glucose, HbA1C, triglycerides and leptin and to increased levels of insulin and adiponectin compared with the vehicle-treated STZ group. The diabetic islets showed retraction from their classic round-shaped as compared with the control islets. The BB-treated groups (at middle and high dosages) showed improvement in islets size and number of Langerhans islet cells. The membrane levels of skeletal muscular glucose transporter 4 (GLUT4) were significantly higher in BB-treated mice. This resulted in a net glucose lowering effect among BB-treated mice. Moreover, BB enhanced the expression of skeletal muscle phospho-AMPK in treated mice. BB-treated mice increased expression of fatty acid oxidation enzymes, including peroxisome proliferator-activated receptor α (PPARα) and mRNA levels of carnitine palmitoyl transferase Ia (CPT1a). These mice also expressed lower levels of lipogenic genes such as fatty acid synthase (FAS), as well as lower mRNA levels of sterol regulatory element binding protein 1c (SREBP1c) and liver adipocyte fatty acid binding protein 2 (aP2). This resulted in a reduction in plasma triglyceride levels. BB-treated mice also expressed lower levels of PPARγ and FAS protein. This led to reduced adipogenesis, fatty acid synthesis and lipid accumulation within adipose tissue, and consequently, to lower triglyceride levels in liver, blood, and adipose tissue. Moreover, BB treatment not only displayed the activation Akt in liver tissue and skeletal muscle, but also in C2C12 myotube to cause an increase in phosphorylation of Akt in the absence of insulin. These results demonstrated that BB act as an activator of AMPK and /or regulation of insulin pathway (Akt), and the antioxidant activity within the pancreas. Therefore, BB treatment ameliorated the diabetic and dyslipidemic state in STZ-induced diabetic mice.

Monascus ruber-Fermented Buckwheat (Red Yeast Buckwheat) Suppresses Adipogenesis in 3T3-L1 Cells.

Although various treatments have been used for weight loss to date, obese people rarely have safe and effective treatment options. Therefore, the antiobesity effects of several natural compounds are being actively investigated. This study was conducted to investigate the antiadipogenic effects of Monascus ruber-fermented Fagopyrum esculentum (red yeast buckwheat, RYB) in 3T3-L1 cells. We assessed the intracellular lipid content and adipocyte differentiation by oil red O staining and the expression of genes and proteins associated with adipocyte differentiation by reverse transcription-polymerase chain reaction and western blotting in 3T3-L1 cells. RYB dose dependently inhibited 3T3-L1 cell differentiation at concentrations of 50-800 μg/mL, without cytotoxic effects. It also suppressed the expression of adipogenic transcription factors, including peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding protein α, and adipocyte-specific genes, such as adipocyte fatty acid-binding protein (aP2), fatty acid synthase, and leptin, during preadipocyte differentiation into adipocytes. Furthermore, RYB reduced cyclin-dependent kinase 2 and cyclin expression and increased p21 and p27 expression, thus causing cell cycle arrest at the G1/S phase. Collectively, these results suggest that RYB may be an effective nutraceutical for weight loss as indicated by its ability to suppress adipogenesis-specific gene expression and cause cell cycle arrest at the G1/S interphase.

Successful reduction of inflammatory responses and arachidonic acid\u2013cyclooxygenase 2 pathway in human pulmonary artery endothelial cells by silencing adipocyte fatty acid-binding protein

BackgroundAdipocyte fatty acid-binding protein, also known as aP2 or fatty acid-binding protein 4 (FABP4), plays an important role in inflammatory and metabolic responses in adipocytes and macrophages. Recent work has demonstrated that macrophage FABP4 integrates inflammatory and lipid metabolic responses, thereby contributing to the development of insulin resistance and atherosclerosis. However, it is not known whether FABP4 in human pulmonary artery endothelial cells(HPAECs) modulates inflammation.ResultsHere, we demonstrate that FABP4 and inflammatory cytokines are upregulated in lipopolysaccharide(LPS)-stimulated HPAECs. In addition, LPS increases the expression of molecules in the arachidonic acid(AA)–cyclooxygenase (COX) 2 signaling pathway in FABP4-expressing, but not FABP4-deficient, HPAECs.ConclusionsOur findings demonstrate that silencing FABP4 could decrease inflammatory cytokines, which were reported to be expressed via the AA–COX2 pathway, in HPAECs. In addition, silencing FABP4 could inhibit the expression of molecules in the AA–COX2 pathways. So we speculate silencing FABP4 could decrease the inflammatory response in HPAECs, which involves in the AA–COX2 signaling pathway. Our study suggests that FABP4 could be a potential biomarker and intervention point for the inflammation-related disease in HPAECs such as pulmonary thromboembolism.

Concentrations of circulating adiponectin and adipocyte-fatty acid binding protein in patients with three-vessel coronary artery disease: a comparison with coronary lesion complexity as characterized by syntax score

Abstract Objective In this study, we investigated the correlation between coronary lesion complexity as characterized by syntax score (SS) with circulating adiponectin and adipocyte-fatty acid binding protein (A-FABP4) concentrations in the presence of stable coronary artery disease affecting three coronary vessels (three-vessel stable CAD). Methods The study groups consisted of 41 control subjects (28 males and 13 females, non-CAD group) and 115 affected subjects (79 males and 36 females, three-vessel stable CAD group). We divided into tertiles the three-vessel stable CAD group according to SS and estimated circulating concentrations of adiponectin and A-FABP4. Results We did not find any correlation between the coronary lesion complexity with either the adiponectin and/or A-FABP4. We found lower the A-FABP4 of the non-CAD group than those of the groups with three-vessel stable CAD (p&lt;0.001). Adiponectin were lower in DM subjects (p&lt;0.05 for each group); though A-FABP4 were found to be higher (p&lt;0.05 for each group) according to non-DM subjects in intra-group comparisons. Conclusion Adiponectin is not a suitable parameter for demonstrating the existence of CAD or predicting coronary lesion complexity. A-FABP4 is more useful for the proof of the presence of CAD but A-FABP4 are not correlated with the severity of CAD.

Serum Level of Adipocyte Fatty Acid Binding Protein in Obesity

Serum Level of Adipocyte Fatty Acid Binding Protein in Obesity