Fatty Acid Binding Protein Research Articles

Gene targets with therapeutic potential in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. Major treatments include liver transplantation, resection, and chemotherapy, but the 5-year recurrence rate remains high. Late diagnosis often prevents surgical intervention, contributing to poor patient survival rates. Carcinogenesis in HCC involves genetic alterations that drive the transformation of normal cells into malignant ones. Enhancer of zeste homolog 2 (EZH2), a key regulator of cell cycle progression, is frequently upregulated in HCC and is associated with advanced stages and poor prognosis, making it a potential biomarker. Additionally, signal transducer and activator of transcription 3, which binds to EZH2, affects disease staging and outcomes. Targeting EZH2 presents a promising therapeutic strategy. On the other hand, abnormal lipid metabolism is a hallmark of HCC and impacts prognosis. Fatty acid binding protein 5 is highly expressed in HCC tissues and correlates with key oncogenes, suggesting its potential as a biomarker. Other genes such as guanine monophosphate synthase, cell division cycle associated 5, and epidermal growth factor receptor provide insights into the molecular mechanisms of HCC, offering potential as biomarkers and therapeutic targets.

Profile of miRNAs induced during sheep fat tail development and roles of four key miRNAs in proliferation and differentiation of sheep preadipocytes

BackgroundThe fat tail of sheep is an adaptive trait that facilitates their adaptation to harsh natural environments. MicroRNAs (miRNAs) have been demonstrated to play crucial roles in the regulation of tail fat deposition.MethodsIn this study, miRNA-Seq was employed to investigate the expression profiles of miRNAs during different developmental stages of sheep fat tails and elucidate the functions of differentially expressed miRNAs (DE miRNAs).ResultsA total of 350 DE miRNAs were identified, among which 191, 60, 26, and 21 were significantly upregulated in tail fat tissues of fetal, lamb, hogget Altay sheep, and adult Xinjiang fine wool (XFW) sheep but downregulated in other stages. Furthermore, we predicted a set of candidate target genes (4,476) for the top 20 DE miRNAs. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that they involve in several adipogenesis-related pathways. Subsequent investigations indicated that four DE miRNAs, miR-433-3p, miR-485-3p, miR-409-3p, and miR-495-3p, could suppress the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) and regulate the preadipocyte development in sheep. Meanwhile, the lipid metabolism-related genes, fatty acid-binding protein (FABP3), perilipin 1 (PLIN1), adiponectin C1Q and collagen domain containing (ADIPOQ), and lipoprotein lipase (LPL), were significantly downregulated (p < 0.01).ConclusionThe expression patterns of miRNAs exhibited significant fluctuations during different development periods of the fat tail, and some of them may participate in the regulation of tail fat deposition by modulating the proliferation and differentiation of preadipocytes.

Beyond Nutritional Treatment: Effects of Fitwalking on Physical Capacity and Intestinal Barrier Integrity in BMI-Stratified IBS Patients

Background: Irritable bowel syndrome (IBS) and obesity are associated with intestinal barrier alterations that result in low-grade inflammation. Zonulin and intestinal fatty acid-binding protein (I-FABP) assess gut barrier health, while urinary indican concentrations reflect dysbiosis in the small intestine. Physical activity, such as Fitwalking, aids weight management and improves intestinal permeability. This study assesses the impact of a 12-week Fitwalking program on intestinal barrier health in IBS patients categorized by body mass index (BMI). Methods: Fifty-seven mild IBS patients were categorized as obese (OB = 18), overweight (OW = 24), or normal weight (NW = 15) and assigned to a walking group. Participants walked thrice weekly at moderate intensity for 60 min per session, using the specific Fitwalking technique, supervised by staff. Results: No significant changes in biochemical or anthropometric variables were observed. However, Fitwalking improved the Global Physical Capacity Score (GPCS) by 46%, 48%, and 24% in the NW, OW, and OB groups. Post-intervention, serum zonulin levels notably decreased in OB individuals, suggesting reduced inflammation. OW patients unexpectedly showed increased fecal zonulin levels. OB participants experienced decreased urinary indican levels. Zonulin levels positively correlated with BMI and inversely with GPCS. Conclusions: Regular exercise benefits the intestinal barrier, especially in obese IBS patients. Monitoring zonulin and I-FABP may offer insights into gut barrier integrity and GI injury severity. Future studies should explore longer intervention durations, larger populations, and advanced diagnostic tools to validate findings and investigate the mechanisms behind exercise-induced changes in intestinal permeability and gut health markers.

Bailing capsule alleviates autoimmune thyroiditis regulating peroxisome proliferator-activated receptor signaling pathway: a multi-omics analysis.

To investigate the efficacy and potential mechanism of Bailing capsule (, BL) anti-autoimmune thyroiditis (AIT). Based on the AIT rat model, the effect of BL in alleviating AIT was evaluated by detecting serum thyroid index free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), thyroglobulin antibody (TGAb), thyroid peroxidase antibody (TPOAb), and inflammatory factors Interferon-gamma (IFN-γ), Interleukin-4, -10, and -12 (IL-4, IL-10, and IL-12) as well as thyroid tissue Hematoxylin-eosin (HE) staining and ultrastructure observation. The mechanism of BL was explored by combining transcriptome and proteome analysis, and further verified by Western blot (WB). BL effectively reduced serum FT3, FT4, TGAb, and TPOAb levels in AIT rats, restored TSH balance, inhibited the release of pro-inflammatory cytokines IFN-γ and IL-12, promoted the production of anti-inflammatory cytokines IL-4 and IL-10, and significantly reduced IFN-γ/IL-4 and IL-12/IL-10, improved thyroid follicular structure, and protected thyroid tissue from injury. Kyoto Encyclopedia of Genes and Genomes and protein interaction network analysis showed that BL affected the expression of fatty acid-binding protein 4, acyl-CoA synthetase long-chain family member 1, and acyl-CoA dehydrogenase long chain to regulate the peroxisome proliferator-activated receptor signaling pathway, thereby inhibiting the fatty acid metabolism and the inflammatory state of AIT rats. BL could effectively reduce thyroid inflammation in AIT model rats. The possible BL mechanism was to regulate the peroxisome proliferator-activated receptor signaling pathway and inhibit fatty acid metabolism. This study suggested that BL has the potential to be used in clinical treatment of AIT.

Evaluation of diagnostic performances of Pro-neurotensin and Heart-type fatty acid binding protein as reliable biomarkers for cardiovascular diseases

ABSTRACT Aim In 2019, cardiovascular diseases accounted for 32% of global deaths. So, early detection of cardiac disorders is crucial. The study aimed to examine the suitability of Pro-neurotensin and Heart-type fatty acid binding protein as dependable biomarkers for cardiac patients with Heart failure as a primary diagnosis. Methodology The prospective study involved 204 Egyptian volunteers (100 cardiac patients and 104 controls) enrolled from El-Sahel Teaching Hospital in Cairo, Egypt, between October 2022 and May 2023. Inclusion criteria included a high risk of cardiovascular events with symptoms like a fast or irregular pulse, shortness of breath, and fatigue. Exclusion criteria included asymptomatic individuals, cognitive disorders, and psychiatric conditions. The Research Ethics Committee approved the protocol. The consultant conducted a clinical examination of all patients and assessed their heart state. Serum ProNT and H-FABP were detected using a kit for the sandwich ELISA technique. Results ProNT and H-FABP were significantly elevated in patients compared to controls with p < 0.001. Demonstrated sensitivity of 81% and 84%, with a specificity of 89% and 91%, respectively. Conclusion Elevated ProNT and H-FABP levels are associated with severe CVDs, suggesting their potential as diagnostic biomarkers for patients, specifically those with heart failure, as a primary characteristic.

Evaluation of expression of amino acid and fatty acid metabolic transporters in the placenta of pregnant women with glucose intolerance.

Pregnant women with glucose intolerance often have large infants, even with strict glycemic control. We examined the expression of amino and fatty acid metabolic transporters in the placentas of such mothers to clarify the role of factors other than glucose transport resulting in giant infants. Deliveries at our hospital between 2017 and 2022 were assessed. Immunohistochemical staining of membrane transporters related to glucose, amino acid, and fatty acid transport was performed using postpartum placental tissue. Stained areas were classified and scored, and compared using the Mann-Whitney U test. Multiple logistic regression analysis was performed for large for gestational age infant as the outcome and maternal age, prepartum body mass index, primipara/multipara, gestational week, and glucose intolerance as confounding factors. Among 1725 subjects, 101 met the inclusion criteria and were analyzed (glucose-intolerant [GI] group, n = 61; non-GI group, n = 40). Per unit villus, there was decreased expression of amino acid-related transporters. However, per unit placenta, the immunohistochemical staining scores for glucose, amino acid, and fatty acid transport were significantly higher in the GI than in the non-GI group. Multiple logistic regression analysis showed that L-type amino acid transporter 1 (LAT1, odds ratio [95% confidence interval]: 12.35 [2.93-52.05], p < 0.001) and placenta-plasma membrane fatty acid-binding protein (placenta-FABPpm, 6.27 [1.64-23.88], p = 0.007) were significantly higher in the GI than in the non-GI group. Activation of LAT1 and placenta-FABPpm expressions observed in the placentas of glucose-intolerant women despite glycemic control indicate that nutrients other than blood glucose should also be effectively managed.

In silico analysis of the action of saturated, monounsaturated, and polyunsaturated fatty acids against Echinococcus granulosus fatty-acid-binding protein 1

Background The zoonotic infection caused by tapeworms Echinococcus is a neglected tropical disease in poor regions with limited access to suitable sanitary conditions. Hydatid cysts produced by Echinococcus granulosus use fatty-acid-binding proteins (FABP) to obtain the fatty acids and cholesterol necessary for their survival from the host. In this work, we analyzed the behaviour of saturated, monounsaturated, and polyunsaturated fatty acids against EgFABP1. Methods We used computational biology and chemistry techniques and binding free energy estimations by molecular mechanics generalized Born surface area (MM/GBSA). Results This research has enabled us to clarify the EgFABP1 isoforms identified in the database, suggesting their potential involvement in diverse cellular activities of Echinococcus granulosus. Conversely, examining the global and local chemical reactivity of 14 fatty acids revealed that liposolubility is contingent upon the degree of unsaturation in the FAs. Additionally, FAs exhibited acceptable levels of oral absorption and bioavailability. The binding of EgFABP1 with FAs analyzed by molecular dynamics simulation showed us that these are highly stable, where the best affinity was with docosahexaenoic acid. Conclusions Our results suggest that the action of fatty acids could play an interesting role in detecting early Echinococcus granulosus.

Olaparib promotes FABP4 expression and reduces antitumor effect in ovarian cancer cells with a BRCA1 mutation.

Olaparib (AZD2281) is used as a first-line maintenance treatment for patients with ovarian cancer (OC) with a breast cancer susceptibility gene (BRCA) mutation. Fatty acid binding protein 4 (FABP4) may serve an important role in cancer, but its role in olaparib-treated OC with a BRCA mutation requires further clarification. To explore the function of FABP4 and enhance the efficacy of AZD2281 in OC, cell counting kit-8, cell apoptosis, cell cycle, colony formation, cell transfection, western blotting, reverse transcription-quantitative polymerase chain reaction, chromatin immunoprecipitation, seahorse and reactive oxygen species assays were performed. In the present study, AZD2281 significantly promoted cell apoptosis, and inhibited cell cycle progression and colony formation in COV362 cells. In addition, AZD2281 significantly upregulated the levels of CCAAT enhancer binding protein α (CEBPα), peroxisome proliferator activated receptor γ (PPARγ) and FABP4. AZD2281 markedly promoted fold enrichment of CEBPα in the promoters of PPARγ and FABP4. Furthermore, FABP4 overexpression significantly decreased cell apoptosis and promoted cell cycle progression and colony formation. In contrast, FABP4 knockdown demonstrated the opposite effects. In addition, FABP4 significantly regulated levels of reactive oxygen species, adenosine triphosphate, aerobic glycolysis, basal respiration rate and fatty acid oxidation. The combination of AZD2281 with the FABP4 inhibitor BM S309403 further significantly increased cell apoptosis and decreased colony formation. In conclusion, the findings of the present study demonstrated that AZD2281 significantly enhanced FABP4 expression, leading to diminished antitumor efficacy in OC cells with a BRCA mutation by regulating CEBPα-PPARγ. Conversely, the combination of AZD2281 and FABP4 inhibitor BM S309403 demonstrated heightened antitumor effectiveness, presenting a promising therapeutic strategy for treating patients with OC with a BRCA mutation.

Neuronal fatty acid-binding protein enhances autophagy and suppresses amyloid-β pathology in a Drosophila model of Alzheimer's disease.

Fatty acid-binding proteins (FABPs) are small cytoplasmic proteins involved in intracellular lipid transport and bind free fatty acids, cholesterol, and retinoids. FABP3, the major neuronal FABP in the adult brain, is upregulated in the CSF of patients with Alzheimer's disease (AD). However, the precise role of neuronal FABPs in AD pathogenesis remains unclear. This study investigates the contribution of fabp, the Drosophila homolog of FABP3 and FABP7, to amyloid β (Aβ) pathology using a Drosophila model. Neuronal knockdown of fabp shortened the lifespan of flies and increased age-related protein aggregates in the brain. In an AD model, fabp knockdown in neurons increased Aβ accumulation and Aβ-induced neurodegeneration, whereas fabp overexpression ameliorated Aβ pathology. Notably, fabp overexpression stimulated autophagy, which was inhibited by the knockdown of Eip75B, the Drosophila homolog of the peroxisome proliferator-activated receptor (PPAR). The PPAR activator rosiglitazone restored autophagy impaired by fabp knockdown and reduced fabp knockdown-induced increased Aβ aggregation and cell death. Furthermore, knockdown of either fabp or Eip75B in the wing imaginal disc or adult fly brain reduced the expression of Atg6 and Atg8a. Additionally, treatment of the fabp knockdown AD model flies with polyunsaturated fatty acids, such as docosahexaenoic acid or linoleic acid, partially alleviated cell death in the developing eye, restored impaired autophagy flux, reduced Aβ aggregation, and attenuated Aβ-induced cell death. Our results suggest that Drosophila fabp plays an important role in maintaining protein homeostasis during aging and protects neurons from Aβ-induced cell death by enhancing autophagy through the PPAR pathway. These findings highlight the potential importance of neuronal FABP function in AD pathogenesis.

Intestinal fatty acid binding protein is associated with coronary artery disease in long-term type 1 diabetes—the Dialong study

BackgroundIndividuals with type 1 diabetes are at increased risk of accelerated atherosclerosis, causing coronary artery disease (CAD). The underlying mechanisms remain unclear, but new theories proposed are damage of gut mucosa causing leakage and translocation of gut microbiota products into the circulation, leading to inflammatory responses and atherosclerosis. We therefore aimed to study the associations between gut related inflammatory biomarkers and coronary atherosclerosis in individuals with long-term type 1 diabetes.MethodsIn this cross-sectional, controlled study of 102 participants with type 1 diabetes and 63 control subjects, we measured circulating levels of intestinal fatty acid binding protein (I-FABP), soluble cluster of differentiation 14 (sCD14), lipopolysaccharide binding protein (LBP) and interleukin 18 (IL-18) by enzyme-linked immunosorbent assay (ELISA), and further gene expression of CD14 and toll-like receptor 4 (TLR4) by real time PCR in circulating leukocytes and peripheral blood mononuclear cells (PBMCs). The participants had either established coronary heart disease (CHD) or underwent computed tomography coronary angiography (CTCA) to assess for coronary atherosclerosis, including total, calcified and soft/mixed plaque volumes.ResultsIn the diabetes group, the levels of I-FABP were significantly higher in participants with established CHD or significant stenosis on CTCA compared to the participants with normal arteries or non-significant stenosis, with median 1.67 ng/ml (interquartile range [IQR] 1.02–2.32) vs. median 1.09 ng/ml (IQR 0.82–1.58), p = 0.003. I-FABP was associated with significant coronary artery stenosis by CTCA (> 50%) or previously established CHD in the adjusted analysis (odds ratio [OR] = 2.32, 95% confidence interval [CI]: 1.09–4.95; p = 0.029). The levels of I-FABP correlated also to total coronary plaque volume (r = 0.22, p < 0.05). This association remained significant after adjusting for age, sex, persistent albuminuria, eGFR, statin treatment, diabetes duration and mean time-weighted variables; HbA1c, LDL-cholesterol and systolic blood pressure (OR = 1.97, 95% CI: 1.28–3.01; p = 0.002).ConclusionsIn this cohort of individuals with long-term type 1 diabetes I-FABP associated significantly with coronary artery stenosis, suggesting a potential role of gut mucosa damage in the process of atherosclerosis in type 1 diabetes.

Temperature and feeding frequency: interactions with growth, immune response, and water quality in juvenile Nile tilapia

BackgroundWater temperature and feeding frequency are critical abiotic factors regulating the growth and immune function of aquatic organisms. This study investigated the effects of water temperature and feeding frequency on growth and immune function in Nile tilapia (Oreochromis niloticus) over two months. A total of 360 juvenile fish (average weight: 20.00 ± 1.26 g) were divided into six groups, each with three replicates, based on a combination of three water temperatures (26, 28, and 30 °C) and two feeding frequencies (either 1 or 2 meals per day).ResultsAt 30 ºC and 28 ºC, water electrical conductivity and total dissolved salts increased, while total ammonia nitrogen and dissolved oxygen rose slightly in groups fed twice daily, with a significant interaction between temperature and feeding frequency. The group at 30 ºC with two meals per day showed the highest final body weight (FBW). The interaction between temperature and feeding frequency significantly influenced FBW, total feed intake, and body thickness. Fish at 30 ºC exhibited upregulated hepatic growth hormone receptor 1 and insulin-like growth factor 1, while those at 28 ºC with one meal per day, as well as those at 30 ºC regardless of meal frequency, also showed increased expression of hepatic fatty acid binding protein and intestinal cluster of differentiation 36. Fish at 30 ºC had upregulated leptin levels and downregulated cholecystokinin, while those at 26 ºC displayed the opposite trend, particularly with one meal daily. Higher temperatures significantly boosted serum IgM, superoxide dismutase (SOD), and lysozyme (LYZ) levels, with meal frequency also affecting malondialdehyde, IgM, and SOD levels. Additionally, 30 ºC enhanced the hepatic expression of mucin-like protein (muc), oligo-peptide transporter 1 (pept1), interleukin 1, nf-κB, complement C3, lyz, sod, catalase, and glutathione peroxidase, with twice-daily meals having a more pronounced effect. Conversely, 28 ºC with one meal per day upregulated some of these genes, such as muc, pept1, and sod.ConclusionsOverall, 30 ºC with two meals per day significantly improved the growth and health of juvenile Nile tilapia, while 28 ºC with two meals maintained satisfactory performance.

Deficiency of FABP7 Triggers Premature Neural Differentiation in Idiopathic Normocephalic Autism Organoids.

Autism spectrum disorder (ASD), which is caused by heterogeneous genetic and environmental factors, is characterized by diverse clinical phenotypes linked to distinct pathological mechanisms. ASD individuals with a shared clinical phenotype might contribute to revealing the molecular mechanism underlying ASD progression. Here, it is generated induced pluripotent stem cell (iPSC)-derived cerebral organoids from normocephalic individuals with ASD in a prospective birth cohort with a shared clinical diagnosis. Multiple cell lines and time series scRNA-seq combined with a histomorphological analysis revealed premature neural differentiation of neural stem cells (NSCs) and decreased expression of Fatty acid binding protein 7 (FABP7) in ASD organoids. It is subsequently revealed alterations in the phosphorylation levels of Mitogen-Activated Protein Kinase Kinase 1/2 (MEK1/2), which are downstream of FABP7, and the regulation of the FABP7/MEK pathway reversed improper neural differentiation in the ASD organoids. Moreover, both Fabp7-knockdown and MEK2-overexpressing mice exhibited repetitive stereotyped behaviors and social defects relevant to autism. This study reveals the role of the FABP7/MEK pathway in abnormal NSC differentiation in normocephalic individuals with ASD, which might provide a promising therapeutic target for ASD treatment.

Liver Fatty Acid-Binding Protein as a Diagnostic Marker for Non-Alcoholic Fatty Liver Disease

Liver Fatty Acid-Binding Protein as a Diagnostic Marker for Non-Alcoholic Fatty Liver Disease

Longitudinal analysis of urinary I-FABP in extremely preterm infants that develop necrotizing enterocolitis.

Intestinal fatty acid binding protein (I-FABP) is an intestinal epithelial protein detectable in infants with necrotizing enterocolitis (NEC). The longitudinal behavior of I-FABP following NEC or its association with gastrointestinal or neurodevelopmental outcomes is unknown. In this secondary analysis of the Preterm Erythropoietin Neuroprotection Trial, we compared infants with and without NEC. Urine I-FABP concentrations in matched infants (n = 70) were measured serially using ELISA and compared using paired analysis. In infants with NEC, the associations of I-FABP levels with short-term outcomes and neurodevelopmental outcomes at 22-26 months corrected age were determined using non-parametric analysis. Infants with NEC were more likely to have cholestasis, death or severe neurodevelopmental impairment, cerebral palsy, and lower Bayley-III motor scores. Baseline urinary I-FABP levels were similar between groups. When compared to controls, infants with NEC had urinary I-FABP concentrations that were higher at diagnosis (median 11 vs 2.6 ng/ml, p = 0.006) and lower post-NEC (median 1 vs 5 ng/ml, p = 0.002). Diagnosis I-FABP levels were not associated with gastrointestinal or neurodevelopmental outcomes at 22-26 months corrected age. In extremely preterm infants, urinary I-FABP was elevated at NEC diagnosis and lower post-NEC compared to matched controls. I-FABP levels were not associated with adverse gastrointestinal or neurodevelopmental outcomes. Urinary intestinal fatty acid binding protein (I-FABP) levels are increased at diagnosis of NEC and fall to below baseline after NEC in extremely preterm infants. Urine I-FABP levels at NEC diagnosis are not associated with cholestasis, intestinal stricture or obstruction, need for additional intestinal surgery after NEC, or neurodevelopmental outcomes at 22-26 months corrected age. Urine I-FABP levels may be useful in the diagnosis of NEC. Diagnostic I-FABP levels do not predict short-term gastrointestinal or neurodevelopmental outcomes after NEC.

Late-gestation maternal undernutrition induces circulatory redistribution while preserving uteroplacental function independent of fetal glycaemic state.

Programming effects of maternal undernutrition on fetal metabolic and cardiovascular systems are well elucidated, yet a detailed characterization of maternal haemodynamics is not available. This study used comprehensive cardiovascular magnetic resonance (CMR) imaging to quantify maternal haemodynamics after 29days (111-140 days) of late-gestation undernutrition (LGUN) in pregnant sheep. Control ewes received 100% of metabolizable energy requirements (MERs, n=15), whereas LGUN ewes were globally nutrient restricted to 50% MER (n=18), with a subset of fetuses undergoing continuous glucose infusion (LGUN+G, n=6/18). Ewes underwent CMR (138-140 days' gestation), and placental tissue was collected the next day. Ewes in both LGUN groups had reduced body weight and mean blood glucose concentration across gestation. Ventricular dimensions were lower in both LGUN groups. Uterine artery blood flow (QUtA) was elevated in the LGUN group compared with controls, whereas peripheral blood flow was reduced and further diminished in LGUN+G. Maternal weight change correlated with all haemodynamic parameters across all groups. Uteroplacental oxygen and glucose delivery were increased in LGUN compared to control ewes, whereas uteroplacental oxygen consumption was preserved. LGUN did not impact placental or fetal weight, and markers of brain-sparing physiology were absent. Placental expression of insulin-like growth factors (IGF-1 and IGF-2) and their receptors, glucose, fatty acid (FA) or amino acid transporters and markers of angiogenesis was not impacted. FA transporter expression was positively correlated with QUtA, and FA binding protein correlated negatively with maternal weight change. Maternal cardiovascular adaptations in response to LGUN manifest as preservation of placental growth and function, thereby preserving fetal growth. KEY POINTS: Maternal undernutrition during pregnancy alters fetal metabolic and cardiovascular physiology, but little is known about alterations in maternal haemodynamics. Late-gestation undernutrition (LGUN) and LGUN+G redirected maternal blood flow from the periphery to the uteroplacental unit, concomitantly increasing the delivery of glucose and oxygen to the uteroplacental unit. Substrate transporter expression and uteroplacental oxygen consumption were preserved in LGUN and LGUN+G, suggesting prioritization of the placenta. This study is the first to report detailed maternal haemodynamics in the setting of maternal undernutrition, where placental growth and function were maintained, ultimately preserving fetal oxygen metabolism and growth.

Lactobacillus paragasseri SBT2055 attenuates obesity via the adipose tissue-muscle-gut axis in obese mice

The anti-obesity effects of Lactobacillus paragasseri (L. paragasseri) have been reported, but the exact mechanisms have not been elucidated. There are also no reports on the impact of L. paragasseri on the gut microbiota environment. Recently, the incidence of sarcopenia due to obesity has increased regardless of age, exacerbating metabolic disorders caused by obesity. Therefore, we investigate the beneficial effects of L. paragasseri SBT2055 (LG2055) on obesity along with obese sarcopenia and gut microbiome changes. C57BL/6 J mice were fed a high-fat diet (HFD) and LG2055 (1×108 or 1×1010 CFU/mice, low-dose LG2055 (LP) or high-dose LG2055 (HP), respectively was administered orally. LG2055 supplementation significantly reduced white adipose tissues compared to the HFD group and modified plasma lipid profiles to normal levels. The anti-obesity efficacy of LG2055 was due to increased lipid excretion into feces by reducing the mRNA levels of fatty acid binding protein 1 (Fabp1), fatty acid binding protein 2 (Fabp2), fatty acid transport protein 4 (Fatp4), cluster of differentiation 36 (Cd36), and apolipoprotein 48 (ApoB48) in the small intestine. The body fat reduction inhibits ectopic lipid accumulation in the muscles, leading to improvements in muscle mass, grip strength, hind leg thickness, muscle protein levels, and muscle fiber size in both LP and HP groups. LG2055 increased gut microbiota diversity and elevated the levels of Bacteroidota, resulting in a lower Firmicutes/Bacteroidota ratio compared to the HFD group. Changes in the Bacteroidota showed a negative correlation with body fat and plasma free fatty acid (FFA) while exhibiting a positive correlation with lean body mass, grip strength, and hind leg thickness. Our results demonstrated the anti-obesity effects of LG2055 through the white adipose tissue (WAT)-muscle-gut axis, suggesting its potential as an anti-obesity agent.

Light up heart-type fatty acid binding protein (FABP3) with a novel fluorine-18 labelled selective FABP3 ligand

BackgroundHeart-type fatty acid binding proteins (FABP3) constitute a family of lipid chaperone proteins. They are found in the cytosol and enhance cellular fatty acid solubilisation, transport, and metabolism. FABP3 is highly expressed in the myocardium and is released from myocytes during myocardial damage. As FABP3 content in the myocardium is closely related to the metabolic state of fatty acids, we hypothesised that targeting of FABP3 with a radiolabelled small organic compound would visualise myocardium.ResultsThe selective FABP3 inhibitor, 4-(4-fluoro-2-(1-phenyl-5-(2-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)phenoxy)butanoic acid (LUF), was radiolabelled via a two-step reaction comprising copper-mediated 18F-fluorination of an arylboronic precursor followed by alkaline hydrolysis of the ethoxy protecting group. [18F]LUF was successfully synthesised by automated synthesiser with sufficient activity yields (14.0 ± 1.8 GBq) and high quality (molar activity, > 250 GBq/µmol and radiochemical purity, > 99.6%). Biological assessment of [18F]LUF as an in vivo myocardial imaging agent included evaluations of biodistribution, metabolite analysis, and positron emission tomography (PET) imaging of small animals. [18F]LUF clearly visualised the myocardium with high contrast against background tissues such as the lung and liver. [18F]LUF also showed a high absolute myocardial uptake equivalent to that of the promising myocardial perfusion tracer [18F]flurpiridaz and excellent metabolic stability in the body. These properties are ideal for stable and noise-less imaging of the heart. PET imaging of rat surgical permanent myocardial infarction (MI) and experimental autoimmune myocarditis (EAM) was also performed. [18F]LUF successfully visualised lesions of permanent MI and EAM.ConclusionOur results showed for the first time that the 18F-labelled FABP3 selective small organic compound clearly visualised myocardium with good quality. To determine the clinical utility of [18F]LUF for cardiovascular disease in clinical practice, it will be necessary to evaluate a greater variety of cardiovascular disease models and elucidate the accumulation mechanism, particularly in relation to fatty acid metabolism in the myocardium.

Transportery kwasów tłuszczowych jako potencjalne markery diagnostyczne raka jelita grubego

Colorectal cancer (RJG) is one of the most frequently diagnosed malignant neoplasms: approximately 1.9 million new cases are reported annually. Notwithstanding the advent of techniques for the early detection of RJG and the introduction of novel therapeutic modalities, this disease remains the second leading cause of cancer-related mortality. The results of recent studies highlight the role of fatty acid transporters, including fatty acid translocase/cluster of differentiation 36 (FAT/CD36), fatty acid transport proteins (FATPs), and fatty acid-binding proteins (FABPs), in the pathogenesis of RJG. Changes in serum concentrations and in expression levels in tumor tissue may serve as promising biomarkers for the early diagnosis of the disease and/or the monitoring of its progression and the efficacy of its treatment. Moreover, the fatty acid carriers present a promising avenue for the development of efficacious therapies against RJG.

Novel Biomarkers as Potential Predictors of Decompensated Advanced Chronic Heart Failure-Single Center Study.

Background/Objectives: Heart failure (HF) remains a major therapeutic and diagnostic challenge nowadays. Albeit, acute decompensated HF is associated with several clinical signs such as dyspnea or edema, it remains a challenge to use easy accessible and suitable tools, such as biomarkers, to distinguish between patients at risk for an acute decompensation of their heart failure and compensated, stable HF patients. Existing biomarkers, such as natriuretic peptides or troponin, are not specific and can be elevated due to several other disease conditions, such as myocardial infarction, atrial fibrillation, or valve diseases. Therefore, the aim of this study was to analyze the predictive potential of four novel cardiovascular biomarkers-the soluble urokinase-type plasminogen activator receptor (suPAR), heart-type fatty acid binding protein (H-FABP), vascular cell adhesion molecule 1 (VCAM-1), and growth/differentiation factor 15 (GDF-15) for the detection of cardiac decompensation in patients with HF. Methods: In this study, 146 patients were prospectively enrolled and the serum biomarker concentrations were analyzed using Enzyme Linked Immunosorbent Assay (ELISA). We correlated the biomarker concentrations with clinical and biochemical parameters of all patients and the predictive value for detection of cardiac decompensation was assessed. Results: A significant increase in the levels of suPAR (1.6-fold-change, p < 0.0001), H-FABP (2.2-fold-change, p = 0.0458), VCAM-1 (1.6-fold-change, p < 0.0001), and GDF-15 (1.7-fold-change, p = 0.0009) was detected in all patients with acute decompensated HF in comparison to patients with compensated HF. Univariate logistic regression analysis revealed a significant association of biomarker plasma concentration with the risk for a cardiac decompensation (suPAR: p < 0.0001; VCAM-1: p < 0.0001, H-FABP: p = 0.0458; GDF-15: p = 0.0009). Conclusions: In conclusion, the investigated novel cardiovascular biomarkers suPAR, GDF-15, VCAM-1, and H-FABP could be a valuable tool to facilitate therapeutic decisions in patients with heart failure and suspicion of a cardiac decompensation. Parameters such as renal function should be taken into account. Further studies on novel biomarkers are required to find reliable, sensitive, and specific tools that will enable the early detection of patients with acute decompensation.

Gene Expression Study in Gilthead Seabream (Sparus aurata): Effects of Dietary Supplementation with Olive Oil Polyphenols on Immunity, Metabolic, and Oxidative Stress Pathways.

In an era with an ever-growing population, sustainability and green transition are the main milestones to be considered within the current European Green Deal program, and the recovery of by-products for the integration of feed with bioactive molecules, that are sustainable and with high nutritional value, is an ambitious mission to be explored also in aquaculture. Olive oil extraction produces a range of solid and liquid by-products, in varying proportions depending on the utilized production techniques, all of which are considered as possible pollutants. However, these products are also rich of polyphenols, bioactive molecules with several and well-known beneficial properties (antimicrobic, anti-inflammatory, antioxidant, and immune-modulating). On this basis, this work aimed at evaluating the effects of dietary supplementation with polyphenols derived from olive mill wastewater on growth performance and on gene expression modulation, by means of RT-qPCR assays, in farmed Sparus aurata. Particularly, some target genes of metabolic, immunity, and oxidative stress pathways have been investigated in breeding gilthead seabream. Differential gene expression analysis was carried out, and differences between the control group (n = 9) and the treated one (n = 9) were computed with Student's t test. The results have highlighted that supplemented feed enhanced fish growth, with a significant feed conversion ratio between the two groups. Furthermore, the polyphenol diet had a beneficial impact on gene expression fold with a level of significance for fatty acid binding protein 2, superoxide dismutase 1, and interleukin-12 genes at hepatic or intestinal district. These significant and promising preliminary findings promote, in the future, other investigations on polyphenolic by-products and on their putative or possible re-utilization in fish feeding.