Adipocyte Fatty Acid-binding Protein Research Articles

Serum Levels of Adipocyte Fatty Acid-Binding Protein Are Associated with Rapid Renal Function Decline in Patients with Type 2 Diabetes Mellitus and Preserved Renal Function

BackgroundRecent studies have demonstrated that the levels of adipocyte fatty acid-binding protein (A-FABP) are closely associated with diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). This study aimed to examine the association between serum A-FABP level and rapid renal function decline in patients with T2DM and preserved renal function.MethodsThis was a prospective observational study of 452 patients with T2DM and preserved renal function who had serial measurements of estimated glomerular filtration rate (eGFR). Rapid renal function decline was defined as an eGFR decline of >4% per year. The association between baseline serum A-FABP level and rapid renal function decline was investigated.ResultsOver a median follow-up of 7 years, 82 participants (18.1%) experienced rapid renal function decline. Median A-FABP levels were significantly higher in patients with rapid renal function decline, compared to non-decliners (20.2 ng/mL vs. 17.2 ng/mL, P=0.005). A higher baseline level of A-FABP was associated with a greater risk of developing rapid renal function decline, independent of age, sex, duration of diabetes, body mass index, systolic blood pressure, history of cardiovascular disease, baseline eGFR, urine albumin creatinine ratio, total cholesterol, glycosylated hemoglobin, high-sensitivity C-reactive protein and use of thiazolidinedione, insulin, angiotensin-converting-enzyme inhibitors and angiotensin II-receptor blockers and statin (odds ratio, 3.10; 95% confidence interval, 1.53 to 6.29; P=0.002).ConclusionA high level of serum A-FABP is associated with an increased risk of rapid renal function decline in patients with T2DM and preserved renal function. This suggests that A-FABP could play a role in the progression of DKD in the early stages.

Use of proteomics to identify biomarkers associated with chronic kidney disease and long-term outcomes in patients with myocardial infarction.

Patients with chronic kidney disease (CKD) have poor outcomes following myocardial infarction (MI). We performed an untargeted examination of 175 biomarkers to identify those with the strongest association with CKD and to examine the association of those biomarkers with long-term outcomes. A total of 175 different biomarkers from MI patients enrolled in the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry were analysed either by a multiple reaction monitoring mass spectrometry assay or by a multiplex assay (proximity extension assay). Random forests statistical models were used to assess the predictor importance of biomarkers, CKD and outcomes. A total of 1098 MI patients with a median estimated glomerular filtration rate of 85mLmin-1 /1.73m2 were followed for a median of 3.2years. The random forests analyses, without and with adjustment for differences in demography, comorbidities and severity of disease, identified six biomarkers (adrenomedullin, TNF receptor-1, adipocyte fatty acid-binding protein-4, TNF-related apoptosis-inducing ligand receptor 2, growth differentiation factor-15 and TNF receptor-2) to be strongly associated with CKD. All six biomarkers were also amongst the 15 strongest predictors for death, and four of them were amongst the strongest predictors of subsequent MI and heart failure hospitalization. In patients with MI, a proteomic approach could identify six biomarkers that best predicted CKD. These biomarkers were also amongst the most important predictors of long-term outcomes. Thus, these biomarkers indicate underlying mechanisms that may contribute to the poor prognosis seen in patients with MI and CKD.

A Pea (Pisum sativum L.) Seed Vicilins Hydrolysate Exhibits PPARγ Ligand Activity and Modulates Adipocyte Differentiation in a 3T3-L1 Cell Culture Model.

Legume consumption has been reported to induce beneficial effects on obesity-associated metabolic disorders, but the underlying mechanisms have not been fully clarified. In the current work, pea (Pisum sativum L.) seed meal proteins (albumins, legumins and vicilins) were isolated, submitted to a simulated gastrointestinal digestion, and the effects of their hydrolysates (pea albumins hydrolysates (PAH), pea legumins hydrolysates (PLH) and pea vicilin hydrolysates (PVH), respectively) on 3T3-L1 murine pre-adipocytes were investigated. The pea vicilin hydrolysate (PVH), but not native pea vicilins, increased lipid accumulation during adipocyte differentiation. PVH also increased the mRNA expression levels of the adipocyte fatty acid-binding protein (aP2) and decreased that of pre-adipocyte factor-1 (Pref-1) (a pre-adipocyte marker gene), suggesting that PVH promotes adipocyte differentiation. Moreover, PVH induced adiponectin and insulin-responsive glucose transporter 4 (GLUT4) and stimulated glucose uptake. The expression levels of peroxisome proliferator-activated receptor γ (PPARγ), a key regulator of adipocyte differentiation, were up-regulated in 3T3-L1 cells treated with PVH during adipocyte differentiation. Finally, PVH exhibited PPARγ ligand activity. Lactalbumin or other pea hydrolysates (PAH, PLH) did not exhibit such effects. These findings show that PVH stimulates adipocyte differentiation via, at least in part, the up-regulation of PPARγ expression levels and ligand activity. These effects of PVH might be relevant in the context of the beneficial health effects of legume consumption in obesity-associated metabolic disorders.

α-Linolenic Acid-Enriched Cold-Pressed Perilla Oil Suppress High-Fat Diet-Induced Hepatic Steatosis through Amelioration of the ER Stress-Mediated Autophagy.

Perilla oil has been considered to have excellent potential for treating various diseases due to its contents of beneficial fatty acids, such as α-linolenic acid, oleic acid and linoleic acid. The therapeutic effects and molecular mechanism of an α-linolenic acid-enriched cold-pressed perilla oil (LEP) on hepatic steatosis of an obesity model were investigated by analyzing alterations in fat accumulation and endoplasmic reticulum (ER) stress-mediated autophagy, in high-fat diet (HFD)-induced obesity C57BL/6N mice treated with LEP for 16 weeks. Although no significant alterations were detected in body weight and most organ weights, the liver weight and accumulation of lipid droplets in the liver section were significantly lower in HFD + LEP treated group as compared to the HFD + Vehicle treated group. Reduced mRNA expression levels of adipogenesis and lipogenesis regulating factors, including the peroxisome proliferator-activated receptor (PPAR)γ, CCAAT/enhancer-binding protein (C/EBP)α, fatty acid synthase (FAS), and adipocyte fatty acid-binding protein 2 (aP2) were observed after LEP treatment for 16 weeks, while the levels of lipolysis were remarkably increased in the same group. Moreover, the LEP-treated groups showed suppression of ER stress-regulating factors, such as the C/EBP homologous protein (CHOP), eukaryotic translation initiation factor 2α (eIF2α), inositol-requiring protein 1 (IRE1)α, and Jun-N-terminal kinase (JNK) during anti-hepatic steatosis effects. The expression level of the microtubule-associated protein 1A/1B-light chain 3 (LC3) protein and phosphatidylinositol-3-kinase (PI3K)/AKT/ mammalian target of rapamycin (mTOR) pathway for the autophagy response showed a significant decrease in the HFD+LEP-treated group. Furthermore, ER stress-mediated autophagy was accompanied with enhanced phosphorylation of extracellular signal-regulated kinase (ERK), JNK, and p38 protein in the mitogen-activated protein (MAP) kinase signaling pathway. Taken together, the results of the present study indicate that treatment with LEP inhibits hepatic steatosis in the HFD-induced obese model through regulation of adipogenesis and lipolysis. We believe our results are the first to show that the anti-hepatic steatosis activity of α-linolenic acid from cold-pressed perilla oil might be tightly correlated with the amelioration of ER stress-mediated autophagy.

Increased Serum Adipocyte Fatty Acid-Binding Protein Levels Are Associated with Decreased Sensitivity to Thyroid Hormones in the Euthyroid Population.

Background: Serum adipocyte fatty acid-binding protein (A-FABP) and thyroid hormones are closely associated with metabolic disorders; however, their relationship remains unknown. We aimed at investigating the associations of serum A-FABP levels with single and composite indices of the thyroid system. Methods: The study included 1057 community-based euthyroid participants (age range: 27-81 years) in Shanghai, among whom 601 were women. Serum free triiodothyronine (fT3), free thyroxine (fT4), and thyrotropin (TSH) were measured by electrochemical luminescence immunoassay. The thyroid feedback quantile-based index (TFQI), thyrotropin index (TSHI), and thyrotroph thyroxine resistance index (TT4RI) were calculated to evaluate central sensitivity to thyroid hormones. Peripheral sensitivity to thyroid hormones was evaluated by the fT3 to fT4 ratio (fT3/fT4). Enzyme-linked immunosorbent assay was used to measure serum A-FABP levels. Results: Serum A-FABP levels were 6.41 [95% confidence interval: 6.10-6.74] ng/mL among all subjects. Multiple cardiovascular metabolic risk factors were adjusted in the multivariate linear regression analysis and the multinomial logistic regression analysis (nonordinal). In both sexes, serum A-FABP levels were positively associated with fT4 (men: standardized β = 0.150, p = 0.001; women: standardized β = 0.218, p < 0.001), TFQI (men: standardized β = 0.119, p = 0.009; women: standardized β = 0.165, p < 0.001), and TSHI (men: standardized β = 0.108, p = 0.017; women: standardized β = 0.114, p = 0.005); while they were negatively associated with fT3/fT4 (men: standardized β = -0.122, p = 0.008; women: standardized β = -0.129, p = 0.001). Serum A-FABP levels were not associated with fT3, TSH, or TT4RI. Compared with the first quartile group of TFQI, for every 10 ng/mL increase in A-FABP, the odds ratio (OR) for the third quartile group of TFQI was 2.213 in women (p = 0.035); the ORs for the fourth quartile group of TFQI were 2.614 in men (p = 0.022) and 3.425 in women (p = 0.002). Conclusions: In a euthyroid population, increased serum A-FABP levels were associated with decreased sensitivity to thyroid hormones, suggesting that A-FABP may mediate the "cross-talk" between adipose tissue and the thyroid system.

1936-P: The Role of Adipose Tissue in Intestinal Functions

Introduction: Adipokines regulate whole-body energy homeostasis, insulin sensitivity and immunity by mediating the crosstalk between adipose tissues and multiple tissues, including liver, skeletal muscle, brain, pancreas and intestines. Recent studies revealed that intestines also exhibit insulin resistance and dysregulated immune homeostasis in obese condition. On the other hand, several adipokines including adiponectin and adipocyte fatty acid binding protein have been shown to regulate intestinal function. Here, we aim to investigate the relationship between the adipose tissue and gut homeostasis using lipodystrophy animal models. Methods: We employed our recently developed lipodystrophic mouse model, in which adipocyte MDM2 is genetically deleted (so-called Adipo-MDM2-KO mice). In fat transplantation experiment, subcutaneous fat form their wild type (WT) littermates was transplanted to the Adipo-MDM2-KO mice for 8 weeks. To assess gut permeability, Adipo-MDM2-KO mice and their wild type (WT) littermates were orally gavaged with DX-4000-FITC for 1 hour. Circulating LPS level were measured using the endotoxin assays, which reflects gut permeability and endotoxemia. For assessment of gut morphology, ileum isolated from Adipo-MDM2-KO mice and their WT littermates were subjected to Haemotoxylin and Eosin (H and E) staining. Results and Conclusion: Adipo-MDM2-KO mice exhibited impaired gut barrier function and altered gut microbiota composition when compared with the WT littermates. A higher level of DX-4000-FITC in the serum of Adipo-MDM2-KO mice were detected. In addition, circulating level of LPS was significantly increased in Adipo-MDM2-KO mice. H and E staining showed a change in gut morphology and an increased number of inflammatory cells in the ileum of Adipo-MDM2-KO mice. These results demonstrated that fat loss leads to intestinal dysfunction, therefore, the adipose tissue is required for gut homeostasis. Disclosure K. Long: None. Funding National Natural Science Foundation of China (91857119)

Relationship between Serum Adipocyte Fatty Acid-Binding Protein Levels and Systemic Inflammation in Hemodialysis Patients

Relationship between Serum Adipocyte Fatty Acid-Binding Protein Levels and Systemic Inflammation in Hemodialysis Patients

Adipocyte fatty acid-binding protein exacerbates cerebral ischaemia injury by disrupting the blood-brain barrier.

AimsAdipocyte fatty acid-binding protein (A-FABP) is an adipokine implicating in various metabolic diseases. Elevated circulating levels of A-FABP correlate positively with poor prognosis in ischaemic stroke (IS) patients. No information is available concerning the role of A-FABP in the pathogenesis of IS. Experiments were designed to determine whether or not A-FABP mediates blood–brain barrier (BBB) disruption, and if so, to explore the molecular mechanisms underlying this deleterious effects.Methods and resultsCirculating A-FABP and its cerebral expression were increased in mice after middle cerebral artery occlusion. Genetic deletion and pharmacological inhibition of A-FABP alleviated cerebral ischaemia injury with reduced infarction volume, cerebral oedema, neurological deficits, and neuronal apoptosis; BBB disruption was attenuated and accompanied by reduced degradation of tight junction proteins and induction of matrix metalloproteinases-9 (MMP-9). In patients with acute IS, elevated circulating A-FABP levels positively correlated with those of MMP-9 and cerebral infarct volume. Mechanistically, ischaemia-induced elevation of A-FABP selectively in peripheral blood monocyte-derived macrophages and cerebral resident microglia promoted MMP-9 transactivation by potentiating JNK/c-Jun signalling, enhancing degradation of tight junction proteins and BBB leakage. The detrimental effects of A-FABP were prevented by pharmacological inhibition of MMP-9.ConclusionA-FABP is a key mediator of cerebral ischaemia injury promoting MMP-9-mediated BBB disruption. Inhibition of A-FABP is a potential strategy to improve IS outcome.

Adipocytokines are not associated with gestational diabetes mellitus but with pregnancy status

AimsAdipose tissue-secreted proteins, i.e. adipocytokines, have been identified as potential mediators linking fat mass and adipose tissue dysfunction with impaired glucose homeostasis, alterations in the inflammatory status, and risk of diabetes. The aim of this study was to determine whether seven circulating adipocytokines are associated with gestational diabetes mellitus (GDM) or are altered by metabolic and weight changes during pregnancy itself. MethodsA panel of seven adipocytokines (i.e. adiponectin, adipocyte fatty acid-binding protein, chemerin, leptin, Pro-Enkephalin, progranulin, and Pro-Neurotensin) was quantified in serum in a cross-sectional cohort of 222 women with the following three groups matched for age and body mass index: (i) 74 pregnant women with GDM; (ii) 74 pregnant women without GDM; and (iii) 74 non-pregnant and healthy women. A stepwise statistical approach was used by performing pairwise comparisons, principal component analysis (PCA), and partial least square discriminant analysis (PLS-DA). ResultsFive out of seven adipocytokines were dysregulated between pregnant and non-pregnant women, i.e. adiponectin, chemerin, leptin, Pro-Enkephalin, and progranulin. None of the adipocytokines significantly differed between GDM and non-GDM status during pregnancy. The same five adipocytokines clustered in a principal component representing pregnancy-induced effects. Fasting insulin was the most relevant parameter in the discrimination of GDM as compared to pregnant women without GDM, whereas chemerin and adiponectin were most relevant factors to discriminate pregnancy status. ConclusionsPregnancy status but not presence of GDM can be distinguished by the seven investigated adipocytokines in discrimination analyses.

High Serum Adipocyte Fatty Acid-Binding Protein Is Associated With Peripheral Artery Disease in Peritoneal Dialysis Patients

BACKGROUND: Peripheral arterial disease (PAD) is a vascular disorder wherein peripheral ischemia is caused by arterial obstruction and results in increased events of cardiovascular disease (CVD). Peritoneal dialysis (PD) is an independent predictor of subclinical PAD and the subsequent mortality in patients with end-stage renal disease. Adipocyte fatty acid-binding protein (A-FABP) is a potential biomarker for CVD risk, especially in patients with overt atherosclerosis. This study was conducted to determine the relationship between PAD and fasting serum levels of A-FABP in patients undergoing PD. METHODS: Fasting blood samples were obtained from 66 PD patients. A-FABP levels were measured using a commercially available enzyme immunoassay kit. Ankle-brachial index (ABI) values were measured using the automated oscillometric method. Serum left or right ABI values of ＜ 0.9 were included in the low ABI group. RESULTS: There were 14 patients (21.2%) in the low ABI group. Compared with patients in the control group, those in the low ABI group had a higher prevalence of diabetes (P = 0.045) and higher serum C-reactive protein (P ＜ 0.001) and A-FABP (P ＜ 0.001) levels but lower weekly Kt/V (P = 0.014) and lower normalized protein equivalent of nitrogen appearance (P = 0.034) values. Multivariate logistic regression analysis of the factors that were significantly associated with PAD revealed that A-FABP (odds ratio, 1.038; 95% confidence interval [CI], 1.004-1.074; P = 0.030) was an independent predictor of PAD in PD patients. The area under the curve plotted to estimate the optimal level of A-FABP predicting PAD in PD patients by the receiver operating characteristic curve analysis was 0.757 (95% CI, 0.636-0.854; P = 0.0004). CONCLUSION: This study demonstrated that a higher serum A-FABP level is an independent predictor of PAD in patients undergoing PD.

Clinical Utility of Serum Adipocyte Fatty Acid Binding Protein (A-FABP) in Type 2 Diabetes Mellitus Patients Complicated with Metabolic Syndrome

Abstract Objective The adipocyte fatty acid-binding protein (A-FABP) has been described as a biomarker for adiposity and obesity-related disease. The aim of this study was to assess the association between fasting serum A-FABP level and the development of metabolic syndrome (MetS) among type 2 DM patients. Methods Fasting blood samples were obtained from 60 type 2 diabetic patients for assessment of serum A-FABP level (30 subjects without MetS and 30 subjects with MetS) compared to 30 healthy control subjects recruited from Endocrinology Department, Ain Shams University Hospitals. A-FABP protein was assayed using ELISA technique, MetS component (waist circumference, fasting serum glucose, triglycerides (TG), high density lipoprotein cholesterol (HDL-C) and blood pressure), as well as homeostasis model assessment of insulin resistance (HOMA-IR) and highly sensitive C-reactive protein ( hsCRP) were assayed for all subjects. Results Diabetic persons who had MetS had significantly higher serum A-FABP levels than either without MetS or healthy controls [Median (25-75 percentiles): 10.5(8.25-14.25); 3.4(0.20-6.00) and 1.5(0.78-2.63) respectively ; p &amp;lt; 0.01). However (HOMA-IR) and hsCRP did not show significant difference between diabetic patients with MetS versus diabetic patients without MetS (p &amp;gt; 0.05). Conclusions Our results indicate that serum A-FABP level is an early marker for the development of MetS in type 2 DM patients, thus its assessment could be beneficial in diagnosis of MetS.

SAT-166 Increased Serum Adipocyte Fatty Acid Binding Protein Concentrations Are Associated with Aortic Stiffness in Diabetic Kidney Disease

Adipocyte fatty acid binding protein (A-FABP) is a novel adipokine that contributes to the development of cardiovascular disease because of pro-inflammatory properties. Our study aims to evaluate the correlation between serum A-FABP and aortic stiffness in diabetic kidney disease (DKD). Fasting blood samples were obtained from 96 type 2 diabetes mellitus patients with DKD. DKD is identified clinically by persistently high urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g and/or sustained reduction in estimated glomerular filtration rate (eGFR) below 60 ml/min per 1.73 m2. Carotid-femoral pulse wave velocity (cfPWV) was measured by using pressure applanation tonometry. cfPWV values of > 10 m/s represented the high aortic stiffness group according to the ESH-ESC 2013. Serum A-FABP levels were determined using a commercial enzyme immunoassay. 53 participants (55.2%) fell under the high aortic stiffness group. This group, compared to the control group, showed higher prevalence of male (P = 0.015), older age (P = 0.025), higher systolic blood pressure (P = 0.001), diastolic blood pressure (P = 0.037), urine albumin-to-creatinine ratio (P = 0.007), serum total cholesterol (P = 0.030), low-density lipoprotein cholesterol (P = 0.043), and A-FABP (P < 0.001). After adjusting for factors significantly associated with aortic stiffness using multivariable logistic regression analysis, serum A-FABP [odds ratio = 1.487 (1.210–1.829), P < 0.001] was found to be an independent predictor of aortic stiffness in DKD patients. Multivariable forward stepwise linear regression analysis also showed that serum logarithmically transformed A-FABP level (log-A-FABP, β = 0.587, adjusted R2 change: 0.426, P <0.001) was positively associated with cfPWV values in DKD patients. In this study, serum A-FABP level is found to be positively correlated with cfPWV values and is identified as an independent predictor of aortic stiffness in DKD patients after adjusting for significant confounders.

Inhibition of 3T3-L1 Adipocyte Differentiation by D-allulose

Obesity is a serious problem in modern society and its prevalence continues to increase worldwide, resulting in metabolic disorder related diseases. D-allulose, a sugar substitute, boasts a near-zero calorie value and regulates lipid accumulation. However, the molecular mechanism of D-allulose at the cellular level has not been fully elucidated. In this study, we investigated the effect of D-allulose on 3T3-L1 adipocyte differentiation. D-allulose inhibits differentiation of 3T3-L1 preadipocytes into mature adipocytes, as examined by Oil Red O staining. The mRNA levels of genes involved in lipogenesis, including fatty acid synthase (FAS) and adipocyte fatty acid-binding protein (aP2), were significantly decreased and intracellular triglyceride (TG) content was markedly reduced with D-allulose treatment. We also monitored the activity of major adipogenic transcription factors–CREB, SREBP-1c, and PPARψ–using 3T3-L1 reporter cell lines that were constructed to secrete Gaussia luciferase upon binding of a transcription factor to its DNA binding element. Collectively, D-allulose suppresses adipocyte differentiation and lipid accumulation through regulating adipogenic transcription factors and may have anti-obesity potential.

Fibroblast growth factor 21 regulates lipid accumulation and adipogenesis in goat intramuscular adipocyte

Fibroblast growth factor 21 (FGF21) plays a critical role in the regulation of lipid metabolism; however, its function in goat intramuscular fat (IMF) deposition remains unknown. To explore the role of FGF21 for goat IMF deposition, we performed gain and loss function of FGF21 in intramuscular adipocyte. Our results showed that overexpression of FGF21 mediated by adenovirus inhibits lipid accumulation of goat intramuscular adipocyte, accompanied by down-regulating the mRNA levels of peroxisome proliferator activated receptor γ (PPARγ), adipocyte fatty acid-binding protein 2 (aP2) and sterol regulatory element-binding protein 1 (SREBP1), but up-regulating counterpart of preadipocyte factor1 (Pref1). Conversely, siRNAs knocking down FGF21 promotes the expression of PPARγ and CCAAT/enhancer binding protein-α (C/EBPα) but suppressed that of lipoprotein lipase (LPL) and Pref1. Meanwhile, we found that FGF21 regulates the expression of many KLFs transcription factors, such as KLF3, 7, 9, 11, 14, and 16. These findings demonstrate a key role of FGF21 as a negative factor in the regulation of adipogenic differentiation in goat intramuscular preadipocyte.

Adipocyte Fatty Acid-Binding Protein 4 is Altered in Growth Discordant Dichorionic, but not in Monochorionic Twins.

ContextThe fetal period has a critical and long-lasting impact on the regulation of metabolic processes and a life-long predisposition for obesity and metabolic syndrome. The exact mechanisms are unknown, but epigenetic regulation likely plays a major role. Twins represent an excellent model to study these mechanisms, as they share the same intrauterine environment and similar or even the same genetic information. We examined cord blood levels of adipocyte fatty-acid binding protein 4 (A-FABP or FABP4), a novel adipokine correlated with obesity and metabolic disease in children and adults.ObjectiveTo examine A-FABP levels in the cord blood of twins with concordant and discordant growth and in singletons with intrauterine growth restriction (IUGR).DesignCohort study of 36 twin pairs (25 growth concordant and 11 growth discordant), and 42 singleton pregnancies (28 IUGR and 13 normally grown controls, 1 HELLP).Outcome MeasuresCord blood A-FABP levels measured by enzyme-linked immunosorbent assay (ELISA).ResultsA-FABP levels were higher in the smaller of growth discordant dichorionic (DC) twins versus their co-twins (109.46 ± 62.80 ng/mL vs. 72.93 ± 36.66 ng/mL, P = 0.028). A-FABP was negatively correlated with birth weight and gestational age (P < 0.001), but not with birth weight z-score (P = 0.37).ConclusionsIncreased A-FABP levels might be associated with an increased metabolic risk in growth-restricted (twins) and prematurely born infants.

Decursin and Decursinol Angelate Suppress Adipogenesis through Activation of β-catenin Signaling Pathway in Human Visceral Adipose-Derived Stem Cells.

Visceral adiposity is closely associated with metabolic disorders and cardiovascular diseases. Angelica gigas Nakai (AGN) has been reported to possess anti-obesity effects and higher amounts of coumarin compounds are present in AGN. However, the active compounds suppressing adipogenesis in AGN and mechanisms of action have not been investigated in adipose-derived stem cells (ASCs) isolated from visceral adipose tissue (VAT). Among four coumarin compounds of AGN, decursin (D) and decursinol angelate (DA) significantly inhibited adipocyte differentiation from ASCs. D and DA downregulated CCAAT/enhancer binding protein α (C/EBPα), peroxisome proliferator-activated receptor γ (PPARγ), adipocyte fatty acid binding protein (aP2), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) at both mRNA and protein levels. Next, treatment with adipogenic differentiation medium (ADM) on ASCs downregulated β-catenin expression at protein level, while addition of D and DA could restore protein expression and nuclear translocation of β-catenin suppressed by ADM. D and DA treatment on ADM treated ASCs increased inhibitory phosphorylation of Glycogen synthase kinase (GSK)-3β, thereby preventing β-catenin from degradation. Additionally, si-β-catenin transfection significantly upregulated protein expression of C/EBPα and PPARγ, alleviating the anti-adipogenic effect of D and DA on ADM treated ASCs. Overall, D and DA, active compounds from AGN, suppressed adipogenesis through activation of β-catenin signaling pathway in ASCs derived from human VAT, possibly using as natural anti-visceral adiposity agents.

Adipocytes promote interleukin-18 binding to its receptors during abdominal aortic aneurysm formation in mice.

Obesity is a risk factor of abdominal aortic aneurysm (AAA). Inflammatory cytokine interleukin-18 (IL18) has two receptors: IL18 receptor (IL18r) and Na-Cl co-transporter (NCC). In human and mouse AAA lesions, IL18 colocalizes to its receptors at regions rich in adipocytes, suggesting a role of adipocytes in promoting IL18 actions in AAA development. We localized both IL18r and NCC in human and mouse AAA lesions. Murine AAA development required both receptors. In mouse AAA lesions, IL18 binding to these receptors increased at regions enriched in adipocytes or adjacent to perivascular adipose tissue. 3T3-L1 adipocytes enhanced IL18 binding to macrophages, aortic smooth muscle cells (SMCs), and endothelial cells by inducing the expression of both IL18 receptors on these cells. Adipocytes also enhanced IL18r and IL18 expression from T cells and macrophages, AAA-pertinent protease expression from macrophages, and SMC apoptosis. Perivascular implantation of adipose tissue from either diet-induced obese mice or lean mice but not that from leptin-deficient ob/ob mice exacerbated AAA development in recipient mice. Further experiments established an essential role of adipocyte leptin and fatty acid-binding protein 4 (FABP4) in promoting IL18 binding to macrophages and possibly other inflammatory and vascular cells by inducing their expression of IL18, IL18r, and NCC. Interleukin-18 uses both IL18r and NCC to promote AAA formation. Lesion adipocyte and perivascular adipose tissue contribute to AAA pathogenesis by releasing leptin and FABP4 that induce IL18, IL18r, and NCC expression and promote IL18 actions.

Identification of B Cell Epitopes of Blo t 13 Allergen and Cross-Reactivity with Human Adipocytes and Heart Fatty Acid Binding Proteins.

Cross-reactivity between allergens and human proteins could have a clinical impact in allergic diseases. Blo t 13 is an allergen from the mite Blomia tropicalis, which belongs to the fatty acid binding protein (FABP) family and has structural homology with human FABPs. This work aimed to map B cell epitopes on Blo t 13 and to identify epitopes involved in cross-reactivity with human heart FABP (FABP3) and adipocyte FABP (FABP4). Sera from 25 patients with house dust mite (HDM) allergy that were sensitized to Blo t 13 were used for testing the reactivity of immunoglobulin E (IgE) and IgG to FABP. The epitope mapping of Blo t 13 was performed using overlapping peptides, and cross-reactivity between Blo t 13 and human FABP was analyzed using human sera and anti-Blo t 13 monoclonal antibodies. IgE antibodies to all FABPs were detected in 14/25 serum samples, and IgG was detected in 25/25 serum samples. The cross-reactivity of Blo t 13 was 42% with FABP3 and 48% with FABP4. Two IgE-binding regions were identified in Blo t 13; one between residues 54 and 72 (the main cross-reacting region) and another between residues 111 to 129. Our results suggest that exposure to the Blo t 13 allergen could induce an auto-reactive response to endogenous FABP in allergic patients sensitized to Blo t 13.

Circulating Adipocyte Fatty Acid Binding Protein (A-FABP): Predictor of Metabolic Syndrome in Patients with Type 2DM

AbstractBackground: The circulating portion of adipocyte fatty acid binding protein (A-FABP) acts as a humoral factor potentially controlling inflammatory responses and insulin action in adipocyte. Most individuals with Type 2 diabetes mellitus (2DM) exhibit intra-abdominal obesity, insulin re-sistance and subsequent occurrence of metabolic syndrome (MetS).Aim of Study: This work aimed at evaluating A-FABP as a marker for MetS in type 2DM.Subjects and Methods: The study included (180) subjects divided into group I (120) adult patients with type 2DM diagnosed according to ADA 2016. They were subdivided into subgroup Ia (60 without MetS) and subgroup Ib (60 with MetS). Group II (control group) included (60) age- and sex-matched apparently healthy subjects. Circulating A-FABP was measured by ELISA. In addition, assay of fasting insulin (F.insulin), lipid profile, hsCRP, and calculation of HOMA-IR.Results: Highly significant increase in levels of A-FABP, F.insulin, HOMA-IR and hsCRP was observed in subgroup Ia compared to control group (Z: 5.691,4.902, 5.908, and 0.477; p 0.05). In subgroup Ib, there was a significant positive statistical correlation between A-FABP and weight and BMI (r:0.379 and 0.386, p<0.05; respectively). Stepwise multi-regression analysis indicated that triglycerides and A-FABP are the most sensitive independent predictors of MetS in diabetic patients (F-ratio:64.4 and p<0.001).Conclusion: High serum A-FABP level is strongly asso-ciated with MetS in type 2DM. It is a promising independent marker of MetS and is beneficial in its early diagnosis.

Carcass Production and Single Nucleotide Polymorphism Adipocyte Fatty Acid Binding Protein (A-Fabp) Gene on Cairina moschata

The aim of this study was to determine differences in growth, carcass production and identify polymorphisms of adipocyte fatty acid binding protein (A-FABP) gene in Muscovy ducks from the second generation selection (G2). The research material used 180-day-old Muscovy ducks consisting of male and female ducks with white feathers and male and female ducks with a combination of black and white feathers. Measurement of duck body weight was carried out every week, and ducks are slaughtered at 10 weeks to obtain carcass production data. The data obtained were analyzed by systat-13 program based on variance analysis and Duncan test. The primary design was based on a database of the genebank Cairina moschata adipocyte fatty acid binding protein (A-FABP) gene, exons 1, 2 and partial cds (FJ763338.1). The primary base sequence of the A-FABP gene was the primary forward: 5’-TCTGGGGGTGTTATCTGGAG -3’ and reverse primer: 5’-ATTTGTCAGTGGCTGTGCTG -3’. The sequencing results of PCR products were analyzed using bioedit version 7.7 to determine the presence of the A-FABP gene polymorphism. The results showed that at the same age male Muscovy ducks produced carcass weight, and thickness of breast meat higher than female ducks. Body weight, carcass weight and parts of the carcass (breast, thigh, back, and wings) of a combination black-white feather male ducks higher than the male white feathers. The abdominal fat on all the ducks relatively the same. The A-FABP gene PCR product was at 176 bp. The results of bioedit analysis showed that at 151 bp, base length there was a mutation from Guanin to Adenin in the observed Cairina moschata, both male and female Muscovy ducks with white feathers and black-white combinations. All ducks observed had homozygous AA genotypes. Base changes in SNP c. 151G> A indicate a transition mutation. The study concluded that male Muscovy duck with a combination black-white feathers have highest genetic potential in body weight and carcass production with thick meat breast compared to other ducks. The weight of abdominal fat was relatively the same in male and female manila ducks. The A-FABP gene in manila ducks was monomorphic.