FABP4 Levels Research Articles

Protective Effects of Voluntary Exercise on Hepatic Fat Accumulation Induced by Dietary Restriction in Zucker Fatty Rats.

Weight control based on dietary restriction (DR) alone can cause lipid metabolic failure and progression to fatty liver. This study aimed to investigate the effect of exercise on preventing DR-induced hepatic fat accumulation in Zucker fatty (ZF) rats by focusing on the relationship between adipose tissue lipolysis and hepatic fat uptake. Six-week-old male ZF rats were randomly assigned to obese, DR, or DR with exercise (DR + Ex) groups. The DR and DR + Ex groups were fed a restricted diet, with the latter also undergoing voluntary exercise. After 6 weeks, hepatic fat accumulation was observed in the DR group, whereas intrahepatic fat was markedly reduced in the DR + Ex group. Compared with the obese (Ob) group, the DR group exhibited 2.09-fold expression of hepatic fatty acid translocase (FAT)/CD36 proteins (p < 0.01) and 0.14-fold expression of hepatic fatty acid-binding protein (FABP)1 (p < 0.01). There were no significant differences between the DR + Ex group and the Ob group. FAT/CD36 and hepatic triglyceride (TG) expression levels were strongly positively correlated (r = 0.81, p < 0.001), whereas there was a strong negative correlation between FABP1 and hepatic TG expression levels (r = −0.65, p < 0.001). Our results suggest that hepatic fat accumulation induced by DR in ZF rats might be prevented through exercise-induced modifications in FAT/CD36 and FABP1 expression.

Viburnum stellato-tomentosum Extract Suppresses Obesity and Hyperglycemia through Regulation of Lipid Metabolism in High-Fat Diet-Fed Mice.

The potential biological activities of Viburnum stellato-tomentosum (VS), a plant mainly found in Costa Rica, have yet to be reported. Supplementation of VS extract for 17 weeks significantly decreased body weight gain, fat weight, fasting glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and triglyceride levels in high-fat diet (HFD)-fed C57BL/6J mice. The molecular mechanisms underlying the anti-obesity and glucose-lowering effects of VS extract were investigated. VS extract suppressed adipocyte hypertrophy by regulating lipogenesis-related CCAAT/enhancer-binding protein α (C/EBPα) and insulin sensitivity-related peroxisome proliferator-activated receptor γ (Pparg) expression in adipose tissue (AT) and hepatic steatosis by inhibiting C/EBPα and lipid transport-related fatty acid binding protein 4 (FABP4) expression. VS extract enhanced muscular fatty acid β-oxidation-related AMP-activated protein kinase (AMPK) and PPARα expression with increasing Pparg levels. Furthermore, VS extract contained a much higher content of amentoflavone (AMF) (29.4 mg/g extract) compared to that in other Viburnum species. AMF administration decreased Cebpa and Fabp4 levels in the AT and liver, as well as improved insulin signaling-related insulin receptor substrate 1 (Irs1) and glucose transporter 1 (Glut1) levels in the muscle of HFD-fed mice. This study elucidated the in vivo molecular mechanisms of AMF for the first time. Therefore, VS extract effectively diminished obesity and hyperglycemia by suppressing C/EBPα-mediated lipogenesis in the AT and liver, enhancing PPARα-mediated fatty acid β-oxidation in muscle, and PPARγ-mediated insulin sensitivity in AT and muscle.

Prognostic impact of elevated fatty acid-binding protein 1 in patients with heart failure.

AimsFew biomarkers to evaluate pathophysiological changes in extra‐cardiac tissues have been identified in patients with heart failure (HF). Fatty acid‐binding protein 1 (FABP), also known as liver FABP, is predominantly expressed in the liver. Circulating FABP1 has been proposed to be a sensitive biomarker for liver injury. However, little is known about the potential role of FABP1 as a biomarker for HF.Methods and resultsMeasurements of serum FABP1 and echocardiography were performed in subjects with compensated HF (n = 162) and control subjects without HF (n = 20). Patients were prospectively followed‐up for a composite outcome of all‐cause mortality or HF hospitalization. Compared with control subjects, levels of FABP1 were elevated in HF patients [7.9 (6.4–11.7) vs. 17.6 (10.4–28.9) ng/mL, P < 0.0001]. There were significant correlations between FABP1 levels and estimated right ventricular systolic pressure and right atrial pressure. During a median follow‐up of 12.0 months, there were 55 primary composite endpoints in the HF cohort. The highest FABP1 tertile was associated with a three‐fold increased risk of the composite outcome compared with the lowest tertile [95% confidence interval (1.46–6.68), P = 0.003], but other conventional hepatobiliary markers did not predict the outcome. After adjusting for age, sex, atrial fibrillation, and N‐terminal pro‐B‐type natriuretic peptide levels, serum FABP1 remained independently associated with the outcome. Adding FABP1 to the model based on clinical factors and N‐terminal pro‐B‐type natriuretic peptide significantly improved the prognostic value (global χ 2 20.8 vs. 15.5, P = 0.01).ConclusionSerum FABP1 levels are elevated in compensated HF patients, and the magnitude of elevation is independently associated with pulmonary hypertension, right atrial hypertension, and worse clinical outcomes. FABP1 may serve as a new potential biomarker for the assessment of hitherto unrecognized derangement of cardio‐hepatic interaction in HF.

Elevated plasma fatty acid-binding protein 3 is related to prolonged corrected QT interval and reduced ejection fraction in patients with stable angina

Background: Higher concentrations of plasma fatty acid-binding protein 3 (FABP3) play a role in the development of cardiovascular events, cerebrovascular deaths, and acute heart failure. However, little is known about the relationship between plasma FABP3 level and prolonged QT interval and reduced ejection fraction (EF). This study aimed to investigate the relationship between plasma FABP3 level and prolonged corrected QT (QTc) interval and reduced EF in patients with stable angina. Inflammatory cytokine and adipocytokine levels were also measured to investigate their associations with plasma FABP3.Methods: We evaluated 249 consecutive patients with stable angina. Circulating levels of FABP3 were measured by ELISA. In addition, 12-lead ECG and echocardiography recordings were obtained from each patient.Results: Multiple regression analysis showed that high-density lipoprotein cholesterol, high sensitivity C-reactive protein (hs-CRP), white blood cell (WBC) count, visfatin, adiponectin, FABP4, heart rate, QTc interval, left atrial diameter, left ventricular mass index, end-systolic volume, end-systolic volume index, fractional shortening, and EF were independently associated with FABP3 (all p<0.05). Patients with an abnormal QTc interval had a higher median plasma FABP3 level than those with a borderline and normal QTc interval. With increasing FABP3 tertiles, the patients had higher frequencies of abnormal QTc interval, left ventricular systolic dysfunction, and all-cause mortality, incrementally lower EF, higher WBC count, and higher levels of hs-CRP, visfatin, adiponectin, and FABP4.Conclusion: This study indicates that plasma FABP3 may act as a surrogate parameter of prolonged QTc interval and reduced EF in patients with stable angina, partially through the effects of inflammation or cardiomyocyte injury. Further studies are required to elucidate whether plasma FABP3 plays a role in the pathogenesis of QTc prolongation and reduced EF.

Impact of rapeseed pomace extract on markers of oxidative stress and DNA damage in human SH-SY5Y cells.

With increased longevity and subsequent rise in people with age-related neurodegenerative diseases, protection of neurons from oxidative stress damage has become an important field of study. For the first time, we highlight the neuroprotective properties of rapeseed pomace (RSP) extract in SH-SY5Y human neuroblastoma cells. We used resazurin to determine cell metabolism, 2,7'-dichlorofluorescin diacetate (H2 DCFDA) to assess the potential of RSP extracts to shield cells from reactive oxygen species (ROS) induced by H2 O2 using flow cytometry, HPLC to analyze for malondialdehyde (MDA) as a lipid peroxidation marker and the COMET assay to assess DNA strand breakage. Protein stress arrays were used to investigate the cellular pathways affected by RSP extract. No effect on cell metabolism in SH-SY5Y cells was observed after RSP extract treatment (up to 1.5mg/ml). Pretreatment (24hr) with RSP extract (1mg/ml), before H2 O2 -induced stress, alleviated ROS production and DNA strand breakage by 68%, and 38%, respectively. At protein level, the RSP extract increased the levels of FABP-1, HIF-1α, SOD2, and Cytochrome c proteins. Under H2 O2 -induced stress, however, it helped to downregulate p38α levels, a protein kinase which is receptive to stress impulse (mitogen-activated). RSP extract shows very promising cell protective properties in relation to oxidative stress. PRACTICAL APPLICATIONS: Oxidative stress has been associated with numerous diseases for example cancer, diabetes, and many neurological disorders including Parkinson's and Alzheimer's diseases. Hence, there is acceptance among the scientific community of antioxidant therapy and the quest for effective, low cost and readily available sources of natural antioxidants is paramount. Rapeseed plantations are abundant around the world due to the use of rapeseed oil in cooking and as a biofuel. The resulting rapeseed pomace (by-product), specifically its extract, contains high levels of phytochemicals that protect cells against oxidative stress. Therefore, RSP extract can potentially be used/developed as functional food and nutraceuticals in the prevention of many complex neurodegenerative diseases.

ZIF-8 Modified Polypropylene Membrane: A Biomimetic Cell Culture Platform with a View to the Improvement of Guided Bone Regeneration.

PurposeDespite the significant advances in modeling of biomechanical aspects of cell microenvironment, it remains a major challenge to precisely mimic the physiological condition of the particular cell niche. Here, the metal–organic frameworks (MOFs) have been introduced as a feasible platform for multifactorial control of cell-substrate interaction, given the wide range of physical and mechanical properties of MOF materials and their structural flexibility.ResultsIn situ crystallization of zeolitic imidazolate framework-8 (ZIF-8) on the polydopamine (PDA)-modified membrane significantly raised surface energy, wettability, roughness, and stiffness of the substrate. This modulation led to an almost twofold increment in the primary attachment of dental pulp stem cells (DPSCs) compare to conventional plastic culture dishes. The findings indicate that polypropylene (PP) membrane modified by PDA/ZIF-8 coating effectively supports the growth and proliferation of DPSCs at a substantial rate. Further analysis also displayed the exaggerated multilineage differentiation of DPSCs with amplified level of autocrine cell fate determination signals, like BSP1, BMP2, PPARG, FABP4, ACAN, and COL2A. Notably, osteogenic markers were dramatically overexpressed (more than 100-folds rather than tissue culture plate) in response to biomechanical characteristics of the ZIF-8 layer.ConclusionHence, surface modification of cell culture platforms with MOF nanostructures proposed as a powerful nanomedical approach for selectively guiding stem cells for tissue regeneration. In particular, PP/PDA/ZIF-8 membrane presented ideal characteristics for using as a barrier membrane for guided bone regeneration (GBR) in periodontal tissue engineering.

Gender-dependent regulation of FABP4 and leptin according to atrial fibrillation burden

Abstract Aims Adiposity plays a key role in the pathogenesis of atrial fibrillation (AF). Its associated proteins are differentially released between male and female. FABP4 and leptin are mediators in adipose tissue-inflammatory effects. Our aim was to study their gender differential behavior on mechanisms associated with AF progression. Methods and results Two independent cohorts were analyzed: A) patients referred for AF catheter ablation (n=217) and patients with suspected coronary artery disease referred for a CT scan (without previous history of AF) (n=105). Protein levels were determined by multiplex fluorometric immunoassay. Gene mRNA expression was analyzed by real time polymerase chain reaction. Correlation between biomarkers was explored with heatmaps and Kendall correlation coefficients. Logistic regression and random forest model determined the best predictors of AF recurrence after catheter ablation. Our results showed: 1) a distinctive profile according to gender, with an increment of FABP4 levels in women (20±14, 29±18 and 31±17 ng/mL; p=0.007) and a decrease of leptin levels in men (22±15, 13±16 and 13±11 ng/mL; p=0.001) among control, paroxysmal and persistent AF groups, respectively; 2) sex differences regarding inflammatory profile, oxidative stress and autonomic indirect markers in AF; 3) a prominent role of adipokines to discriminate AF recurrence after ablation. In persistent AF, FABP4 was the best predictor (LR coefficient 1.067, 95% CI 1–1.14, p=0.046). Conclusion The major finding of the present study is the sex differences of FABP4 and leptin according to AF burden. The relationship of these adipokines with oxidative stress, inflammatory and autonomic indirect markers might explain part of the mechanisms underlying the AF perpetuation. Adipokines regarding Gender &amp; AF burden Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Institute of Health Carlos III

Beige adipocytes contribute to breast cancer progression.

Adipocytes are the main stromal cells in the mammary microenvironment, and crosstalk between adipocytes and breast cancer cells may play a critical and important role in cancer maintenance and progression. Tumor‑induced differentiation to beige/brown adipose tissue is an important contribution to the hypermetabolic state of breast cancer. However, the effect of epithelial cell‑beige adipocyte communication on tumor progression remains unclear. To contribute to the understanding of this phenomenon, we characterized components present in conditioned media(CM) from beige adipocytes (BAs) or white adipocytes(WAs), and evaluated the effects of BA‑ and WA‑CM on both adhesion and migration of tumor (LM3, 4T1 and MC4‑L1) and non‑tumor (NMuMG) mouse mammary epithelial cell lines. Additionally, we analyzed the expression of ObR, CD44, vimentin, MMP‑9, MCT1 and LDH in tumor and non‑tumor mouse mammary epithelial cell lines incubated with BA‑CM, WA‑CM or Ctrol‑CM (control conditioned media). 3T3‑L1 preadipocytes differentiated into beige adipocytes upon PPARγ activation (rosiglitazone) displaying characteristics that morphologically resembled brown/beige adipocytes. Levels of UCP1, CIDEA, GLUT4, leptin, MCT4 and FABP4 were increased, while adiponectin, caveolin 1 and perilipin 1 levels were decreased in BAs with respect to WAs. Tumor cell lines revealed lower cell adhesion and increased cell migration after incubation with BA‑ and WA‑CM vs. Ctrol‑CM. ObR and MMP‑9 in MC4‑L1 cells were significantly increased after incubation with BA‑CM vs. WA‑ and Ctrol‑CM. In addition, MC4‑L1 and LM3 cells significantly increased their migration in the presence of BAs, suggesting that new signals originating from the crosstalk between BAs and tumor cells, could be responsible for this change. Our results indicate that beige adipocytes are able to regulate the behavior of both tumor and non‑tumor mouse mammary epithelial cells, favoring tumor progression.

The Relationship Between the Level Fabp4, Risks of Type 2 Diabetes Mellitus, and Cardiovascular Events

BACKGROUND: The normoglycemic patients with diabetes risk and prediabetes have insulin resistance and consequently endothelial dysfunction that possible causes macroangiopathy and adverse cardiovascular events and further mortality of it. An early diabetes risk identification using not only prognostic scales but also biomarkers is starting and crucial point of struggle with 2 type diabetes mellitus and its complications.&#x0D; AIM: The aim of the study is to estimate the impact of FABP4 biomarker on diabetes risk and cardiovascular events.&#x0D; METHODS: A cross-sectional study was conducted simultaneously among 389 respondents aged 18–65 years. We provided survey and clinical examinations. The risk of diabetes was assessed using the FINDRISC scale and cardiovascular risk (CVR) was assessed using SCORE scale.&#x0D; The serum FABP4 biomarker was studied using a multiplex assay, immunofluorescence using XMap technology, a Bioplex 3D instrument, and a MILLIPLEX® Human cardiovascular disease panel I reagent kit(Millipore). Results were considered statistically significant at p &lt; 0.001.&#x0D; RESULTS: The group of type 2 diabetes mellitus (T2DM) high risk was 79 (20%) of all study participants. The level of the FABP4 marker significantly prevailed in high-risk group of T2DM and high CVR was also established this group. We found a positive direct average correlation(r = 0.59; p = 0.000) between FABP4 and FINDRISC scale. The logistic regression analysis indicated that the level of the FABP4 marker increases withing the increased risk of T2DM. The correlation between FABP4 concentration and CVR according to the SCORE scale (r = 0.24; p = 0,000) was lower than between FABP4 and diabetes risk. Risk factors were established affecting on the increasing CVR by SCORE scale in patients with T2DM risk.&#x0D; CONCLUSIONS: The level of FABP4 significantly prevailed in the group of diabetes and cardiovascular risk (CVR). The established correlations between FABP4 level and CVR or T2DM risk indicate on its increase in groups with a higher risk of type 2 diabetes and a high CVR.

Elevated expression of FABP4 is associated with disease activity in rheumatoid arthritis patients.

Aim: Data from 124 rheumatoid arthritis (RA) patients and 69 healthy controls were collected. Materials & methods: ELISA was performed to detect serum FABP4 levels. Results: FABP4 level was elevated in RA patients and positively associated with 28-joint disease activity score, high-sensitivity C-reactive protein, erythrocyte sedimentation rate, total cholesterol, triglyceride and low-density lipoprotein cholesterol. Additionally, the area under the receiver operating characteristic curve for FABP4 was 0.685 for RA patients versus healthy controls (p = 0.001). RA patients were separated into low, moderateand high disease activity based on 28-joint disease activity score. The area under the receiver operating characteristic value was 0.877 for RA patients with high disease activity versus healthy controls (p < 0.001). Conclusion: FABP4 was associated with disease activity in RA patients.

Independent and Distinct Associations of FABP4 and FABP5 With Metabolic Parameters in Type 2 Diabetes Mellitus.

Objective: Among fatty acid-binding proteins (FABPs), secreted forms of FABP4 and FABP5, which are expressed in adipocytes and macrophages, act as bioactive molecules. We investigated concentrations of FABP4 and FABP5 in patients with type 2 diabetes mellitus.Methods: As a sub-analysis study of the Randomized Evaluation of Anagliptin vs. Sitagliptin On low-density lipoproteiN cholesterol in diabetes (REASON) trial, 256 patients (male/female: 146/110, age: 68 ± 10 years) with type 2 diabetes mellitus and dyslipidemia who were receiving statin therapy were recruited. Patients who had been treated with a thiazolidinedione were excluded.Results: Several drugs which may modulate FABP4 levels including statins, dipeptidyl peptidase-4 inhibitors and angiotensin II receptor blockers had been administered in 100, 81, and 51% of the recruited patients, respectively. The level of FABP4, but not that of FABP5, was significantly higher in females than in males. Multivariable linear regression analysis demonstrated that waist circumference (β = 0.21), estimated glomerular filtration rate (β = −0.31), triglycerides (β = 0.16), and FABP5 (β = 0.39) were independent predictors of FABP4 level after adjusting age and sex. On the other hand, FABP5 level was independently associated with levels of FABP4 (β = 0.57) and high-density lipoprotein (HDL) cholesterol (β = −0.12).Conclusions: Concentrations of FABP4 and FABP5 are independent predictors of each other in patients with type 2 diabetes mellitus. There are distinct independent associations of FABP4 with renal dysfunction, adiposity and hypertriglyceridemia and there is a distinct independent association of FABP5 with a low HDL cholesterol level in type 2 diabetic patients with dyslipidemia at high risks for cardiovascular disease who are receiving statin therapy.

Predicting Nonalcoholic Fatty Liver Disease through a Panel of Plasma Biomarkers and MicroRNAs in Female West Virginia Population.

(1) Background: Nonalcoholic fatty liver disease (NAFLD) is primarily characterized by the presence of fatty liver, hepatic inflammation and fibrogenesis eventually leading to nonalcoholic steatohepatitis (NASH) or cirrhosis. Obesity and diabetes are common risk factors associated with the development and progression of NAFLD, with one of the highest prevalence of these diseased conditions in the West Virginia population. Currently, the diagnosis of NAFLD is limited to radiologic studies and biopsies, which are not cost-effective and highly invasive. Hence, this study aimed to develop a panel and assess the progressive levels of circulatory biomarkers and miRNA expression in patients at risk for progression to NASH to allow early intervention strategies. (2) Methods: In total, 62 female patients were enrolled and blood samples were collected after 8–10 h of fasting. Computed tomography was performed on abdomen/pelvis following IV contrast administration. The patients were divided into the following groups: Healthy subjects with normal BMI and normal fasting blood glucose (Control, n = 20), Obese with high BMI and normal fasting blood glucose (Obese, n = 20) and Obese with high fasting blood glucose (Obese + DM, n = 22). Based on findings from CT, another subset was created from Obese + DM group with patients who showed signs of fatty liver infiltration (Obese + DM(FI), n = 10). ELISA was performed for measurement of plasma biomarkers and RT-PCR was performed for circulating miRNA expression. (3) Results: Our results show significantly increased levels of plasma IL-6, Leptin and FABP-1, while significantly decreased level of adiponectin in Obese, Obese + DM and Obese + DM(FI) group, as compared to healthy controls. The level of CK-18 was significantly increased in Obese + DM(FI) group as compared to control. Subsequently, the expression of miR-122, miR-34a, miR-375, miR-16 and miR-21 was significantly increased in Obese + DM and Obese + DM(FI) group as compared to healthy control. Our results also show distinct correlation of IL-6, FABP-1 and adiponectin levels with the expression of miRNAs in relation to the extent of NAFLD progression. (4) Conclusion: Our results support the clinical application of these biomarkers and miRNAs in monitoring the progression of NAFLD, suggesting a more advanced diagnostic potential of this panel than conventional methods. This panel may provide an appropriate method for early prognosis and management of NAFLD and subsequent adverse hepatic pathophysiology, potentially reducing the disease burden on the West Virginia population.

Hepatic Lipidomics and Molecular Imaging in a Murine Non-Alcoholic Fatty Liver Disease Model: Insights into Molecular Mechanisms.

An imbalance between hepatic fatty acid uptake and removal results in ectopic fat accumulation, which leads to non-alcoholic fatty liver disease (NAFLD). The amount and type of accumulated triglycerides seem to play roles in NAFLD progression; however, a complete understanding of how triglycerides contribute to NAFLD evolution is lacking. Our aim was to evaluate triglyceride accumulation in NAFLD in a murine model and its associations with molecular mechanisms involved in liver damage and adipose tissue-liver cross talk by employing lipidomic and molecular imaging techniques. C57BL/6J mice fed a high-fat diet (HFD) for 12 weeks were used as a NAFLD model. Standard-diet (STD)-fed animals were used as controls. Standard liver pathology was assessed using conventional techniques. The liver lipidome was analyzed by liquid chromatography–mass spectrometry (LC–MS) and laser desorption/ionization–mass spectrometry (LDI–MS) tissue imaging. Liver triglycerides were identified by MS/MS. The transcriptome of genes involved in intracellular lipid metabolism and inflammation was assessed by RT-PCR. Plasma leptin, resistin, adiponectin, and FABP4 levels were determined using commercial kits. HFD-fed mice displayed increased liver lipid content. LC–MS analyses identified 14 triglyceride types that were upregulated in livers from HFD-fed animals. Among these 14 types, 10 were identified in liver cross sections by LDI–MS tissue imaging. The accumulation of these triglycerides was associated with the upregulation of lipogenesis and inflammatory genes and the downregulation of β-oxidation genes. Interestingly, the levels of plasma FABP4, but not of other adipokines, were positively associated with 8 of these triglycerides in HFD-fed mice but not in STD-fed mice. Our findings suggest a putative role of FABP4 in the liver-adipose tissue cross talk in NAFLD.

Jateorhizine alleviates insulin resistance by promoting adipolysis and glucose uptake in adipocytes

Jateorhizine (Jat) can reduce blood glucose in diabetic mice, but there are few studies on its role in insulin resistance (IR). This study analyzed the effect of Jat on adipocytes, so as to provide an evidence for the clinical application of Jat. MDI was used to differentiate preadipocytes into adipocytes and induce IR cell models. Different concentrations of Jat (1, 5, 10, 20 μmol/L) were added into undifferentiated and differentiated cells. The cell viability was detected using MTT method. Oil red O staining was performed to observe the lipid formation in cells. Adipolysis method was used to detect the release of glycerol in cell culture medium. The level of 2-DG in cells was detected by glucose uptake assay based on insulin treatment. The expression of adipose transcription factors and IRS2/p-PI3K/p-AKT/GLUT4 signaling pathway was analyzed by western blot (WB) analysis. Neither the activity of differentiated nor undifferentiated preadipocytes was affected by the addition of Jat. There was numerous lipid formation in cells induced by MDI, which was decreased visibly by Jat. Jat reduced the expression levels of MDI-induced elevated levels of PPARγ, C/EBPα, FABP4, perilipin and FAS, as well as increased the release of glycerol in adipocytes. Moreover, Jat further enhanced the 2-DG uptake in MDI-induced adipocytes, and activated the IRS2/p-PI3K/p-AKT/GLUT4 signaling pathway. In general, the role of Jat in adipocytes was concentration-dependent. Jat can not only promote adipolysis, but also increase the glucose uptake in adipocytes, which might be a potential therapy for IR.

Serum Fatty Acid Binding Protein 4 in Patients with Androgenetic Alopecia

Androgenetic alopecia (AGA) is the most common cause of hair loss. Adipocyte fatty acid-binding protein (FABP4), also termed adipocyte protein 2 (aP2), is an adipokine synthesized and released predominantly from adipocytes and, to a lesser extent, produced in macrophages and endothelial cells. Elevated levels of FABP4 are closely linked with the development of obesity, DM, hypertension and atherosclerosis. we aimed to assess the level of serum FABP4 in patients with AGA. This case-control study was conducted on thirty male patients and twenty female patients complaining of androgenetic alopecia, and thirty age and BMI matched healthy volunteers. Patients were recruited from outpatient clinic of Dermatology, Venereology and Andrology Department of Benha University Hospitals during the period from December 2017 to June 2018.All participants were tested for determination of fatty acid binding protein 4 serum levels. AGA patients showed significantly higher FABP4 levels when compared to controls. Serum FABP4 level was significantly higher in AGA patients than in control group so it might play a role in androgenetic alopecia pathogenesis. Moreover, it could be considered a biomarker for early diagnosis of the disease with high sensitivity, specificity and accuracy rate.

Molecular cloning, tissue expression, and transcriptional regulation of fabp1 and fabp2 in javelin goby (Synechogobius hasta) in response to starvation stress.

Fatty acid binding proteins (FABPs) are intracellular lipid chaperones with low molecular weight, which are widely distributed in a variety of tissues, participating in fatty acid transport, cell proliferation, and angiogenesis. In this study, full-length sequences of two fabp genes (fabp1 and fabp2) from javelin goby (Synechogobius hasta) were cloned via RACE PCR, followed by bioinformatic analyses and gene expression evaluation. The fabp1 and fabp2 cDNA sequences were 493 and 626bp in length, encoding 126 and 132 amino acids, respectively. Phylogenetic analysis revealed that both genes from S. hasta were clustered with those of other fish species in accordance with their known taxonomic relationships. fabp1 and fabp2 mRNA showed distinct expression patterns in different tissues, with fabp1 being most expressed in the liver and fabp2 in the intestine. Furthermore, the expression of fabp1 in the liver was significantly up-regulated during starvation, whereas fabp2 mRNA level in the intestine initially increased and then decreased, indicating that the transcriptional responses of the two genes could be influenced by malnourishment/starvation. Changes in the transcriptional levels of fabp1 and fabp2 also suggested that glycogen was catabolized in the liver of S. hasta at the beginning of starvation prior to lipid depletion, whereas lipids served as fuel reserves in the intestine during short-term starvation. In conclusion, this study provides fundamental insights into the role of Fabps in S. hasta lipid metabolism.

SOCS2 Inhibits Mitochondrial Fatty Acid Oxidation via Suppressing LepR/JAK2/AMPK Signaling Pathway in Mouse Adipocytes.

Suppressor of cytokine signaling 2 (SOCS2) plays an important role in fat deposition, skeletal muscle, central nervous system development, and mitochondria biogenesis. Nevertheless, the regulatory mechanisms of SOCS2 on mitochondrial fatty acid oxidation (FAO) remain unclear. Leptin could inhibit food intake and increase thermogenesis through leptin receptor (LepR), which was present in the hypothalamus and certain peripheral organs, including adipose tissue. With strong interest, we focused on the connection between leptin and SOCS2 and their effect on FAO in adipocytes. In our study, we found that the mRNA level of SOCS2 and the protein levels of PGC-1α, CPT-1b, FAT, and p-ACC were elevated by leptin in the inguinal adipose tissue of mice. On the contrary, the protein levels of FABP4, FATP1, and FAS were declined. The genes related to fatty acid oxidation such as PGC-1α, NRF-1, TFAM, CPT-1b, AOX1, COX2, and UCP2 were attenuated by SOCS2, but elevated by leptin. Moreover, fatty acid oxidation enzyme MCAD, LCAD, and Cyt C levels were reduced in response to SOCS2. These reductions correspond well with the reduced release of free fatty acid and the reduction of mitochondrial complexes I and III by SOCS2. Furthermore, JAK2/AMPK pathway-specific inhibitors could block the mitochondrial FAO; hence, this pathway was implied to have a potential impact on FAO. Together, these studies suggested that SOCS2 had a negative effect on mitochondrial fatty acid oxidation, and the LepR/JAK2/AMPK pathway played a crucial role in this process.

Integration of organ metabolomics and proteomics in exploring the blood enriching mechanism of Danggui Buxue Decoction in hemorrhagic anemia rats

Ethnopharmacological relevanceDanggui Buxue Decoction (DBD), as a classical Chinese medicine prescription, is composed of Danggui (DG) and Huangqi (HQ) at a ratio of 1:5, and it has been used clinically in treating anemia for hundreds of years. Aim of the studyThe aim of this study was to explore the treatment mechanisms of DBD in anemia rats from the perspective of thymus and spleen. Materials and methodsIn this study, a successful hemorrhagic anemia model was established, and metabolomics (UPLC-QTOF-MS/MS) and proteomics (label-free approach) together with bioinformatics (Gene Ontology analysis and Reactome pathway enrichment), correlation analysis (pearson correlation matrix) and joint pathway analysis (MetaboAnalyst) were employed to discover the underlying mechanisms of DBD. ResultsDBD had a significant blood enrichment effect on hemorrhagic anemia rats. Metabolomics and proteomics results showed that DBD regulated a total of 10 metabolites (lysophosphatidylcholines, etc.) and 41 proteins (myeloperoxidase, etc.) in thymus, and 9 metabolites (L-methionine, etc.) and 24 proteins (transferrin, etc.) in spleen. With GO analysis and Reactome pathway enrichment, DBD mainly improved anti-oxidative stress ability of thymocyte and accelerated oxidative phosphorylation to provide ATP for splenocyte. Phenotype key indexes were strongly and positively associated with most of the differential proteins and metabolites, especially nucleosides, amino acids, Fabp4, Decr1 and Ndufs3. 14 pathways in thymus and 9 pathways in spleen were obtained through joint pathway analysis, in addition, the most influential pathway in thymus was arachidonic acid metabolism, while in spleen was the biosynthesis of phenylalanine, tyrosine and tryptophan. Furthermore, DBD was validated to up-regulate Mpo, Hbb and Cp levels and down-regulate Ca2+ level in thymus, as well as up-regulate Fabp4, Ndufs3, Tf, Decr1 and ATP levels in spleen. ConclusionDBD might enhance thymus function mainly by reducing excessive lipid metabolism and intracellular Ca2+ level, and promote ATP production in spleen to provide energy.

Clinical significance of increased peripheral venous blood adipocyte-specific protein FABP4 after joint replacement

A new method of diagnosing fat embolism (FE) at the molecular level was proposed, and the diagnostic value of adipocyte-specific protein fatty acid-binding protein 4 (Homo sapiens [human]) gene ID = 2167 (FABP4) for FE was preliminarily explored. Eight joint replacement patients, 5 internal medicine patients, and 6 healthy persons were recruited. Serum of internal medicine patients, healthy people, and patients before and 24 hours after joint replacement were taken as study samples. Subcutaneous adipose, intra-articular adipose and intramedullary yellow bone marrow of patients undergoing joint replacement were taken as study samples. The level of FABP4 in the above samples was detected by enzyme-linked immunoassay. Normal distribution was tested. Paired sample T test was used for self-control. Univariate analysis of variance was used for multigroup comparison.There was no significant difference in serum FABP4 level between healthy persons, medical patients, and preoperative patients. The FABP4 level in yellow bone marrow and subcutaneous adipose was significantly higher than that in serum of healthy people, medical patients, and preoperative patients. FABP4 level in the serum after joint replacement was significantly higher than that before joint replacement. FABP4 may be a specific indicator of FE diagnosis, but further studies are needed to confirm its clinical value.

Treatment with anagliptin, a DPP-4 inhibitor, decreases FABP4 concentration in patients with type 2 diabetes mellitus at a high risk for cardiovascular disease who are receiving statin therapy

BackgroundFatty acid-binding protein 4 (FABP4) acts as a novel adipokine, and elevated FABP4 concentration is associated with obesity, insulin resistance and atherosclerosis. Dipeptidyl peptidase-4 (DPP-4) inhibitors, a class of antidiabetic drugs, have distinct structures among the drugs, possibly leading to a drug class effect and each drug effect. Sitagliptin, a DPP-4 inhibitor, has been reported to decrease FABP4 concentration in drug-naïve and sulfonylurea-treated patients with type 2 diabetes mellitus. Anagliptin, another DPP-4 inhibitor, was shown to decrease low-density lipoprotein cholesterol (LDL-C) level to a greater extent than that by sitagliptin in the Randomized Evaluation of Anagliptin vs. Sitagliptin On low-density lipoproteiN cholesterol in diabetes (REASON) trial.Aim and methodsAs a sub-analysis study using data obtained from the REASON trial, we investigated the effects of treatment with anagliptin (n = 148, male/female: 89/59) and treatment with sitagliptin (n = 159, male/female: 93/66) for 52 weeks on FABP4 concentration in patients with type 2 diabetes mellitus at a high risk for cardiovascular events who were receiving statin therapy.ResultsThe DPP-4 inhibitor had been administered in 82% of the patients in the anagliptin group and 81% of the patients in sitagliptin group prior to randomization. Serum FABP4 level was significantly decreased by 7.9% by treatment with anagliptin (P = 0.049) and was not significantly decreased by treatment with sitagliptin (P = 0.660). Change in FABP4 level was independently associated with basal FABP4 level and changes in waist circumference and creatinine after adjustment of age, sex and the treatment group.ConclusionAnagliptin decreases serum FABP4 concentration independent of change in hemoglobin A1c or LDL-C in patients with type 2 diabetes mellitus and dyslipidemia who are on statin therapy.Trial registration ClinicalTrials.gov number NCT02330406. Registered January 5, 2015, https://clinicaltrials.gov/ct2/show/NCT02330406