FABP4 Levels Research Articles

(-)-Epicatechin increases apelin/APLNR expression and modifies proteins involved in lipid metabolism of offspring descendants of maternal obesity

Several studies have shown the beneficial effects of (-)-epicatechin (Epi) in metabolic profile and that this flavanol is a biased ligand of the apelin receptor. The apelinergic system is expressed in adipocytes and has been related to obesity and metabolic disorders. The study aim was to evaluate the effect of Epi on apelin, on its receptor and on proteins involved in lipolysis, lipogenesis, and adipogenesis in the retroperitoneal adipose tissue of male rats descended from obese mothers. We evaluated the effect of Epi in the retroperitoneal adipose tissue of four groups of male offspring, analyzing mRNA expression and protein levels of apelin and its Apj receptor. We also analyzed, by Western Blot, the levels of AMPKα, ACC, C/EBPα, ATGL, Fas, and FABP4 of the AP2 proteins. Epi significantly elevated apelin mRNA expression and protein levels as well as its Apj receptor. Besides, the flavanol significantly promoted AMPKα phosphorylation with the concomitant reduction of Fas, and the increase of the ATGL protein. In contrast, there was an increase in the inactive phosphorylated form of ACC and a decrease in the phosphorylated active form of C/EBPα. Similarly, Epi treatment induced a reduction in the fatty acid-binding protein 4 in the C+Epi and MO+Epi groups.In conclusion, Epi increases the expression of the apelinergic system and the active phosphorylated form of AMPKα; likewise, it modifies the expression level or active form of proteins involved in lipolysis, lipogenesis and adipogenesis in the retroperitoneal adipose tissue of male offspring of obese mothers.

Current Energy and Lipid Metabolism Biomarkers in Sheep with Subclinical And Clinical Pregnancy Toxemia

The aim of this study was to evaluate the relationship between existing metabolic biomarkers (asprosin, FABP1, PPARα and FGF21) and clinical parameters and to determine their role in the early diagnosis of sheep pregnancy toxemia. In the study, 70 Akkaraman sheep aged three to five years in the last three weeks of pregnancy were divided into three groups: healthy group (n = 20), subclinical group (n = 30), and clinical group (n = 20). Clinical examination (body temperature, respiratory rate, and heart rate), blood serum biochemistry, and ELISA analyses were performed. In sheep with clinical and subclinical pregnancy toxemia, serum PPARα, β-HBA, NEFA, HbA1c, HDL, triglyceride, creatinine, and phosphorus levels were statistically higher, whereas serum glucose and LDL levels were lower than in healthy sheep. However, serum FGF21, AST, ALT, and VLDL values were not statistically different between the three groups. In addition, serum asprosin and FABP1 levels were higher in the subclinical group than in the clinical group. Thus it was concluded that serum asprosin, FABP1, and PPARα findings could be useful in evaluating lipid and energy metabolism in subclinical and clinical forms of pregnancy toxemia. Since this study was based on blood samples from individually reared sheep herds, many environmental factors (e.g., housing, nutrition, and population density) could not be considered. For this reason, it is thought that there is a need for experimental studies in which environmental variables can be controlled.

Ginkgo biloba Extract Stimulates Adipogenesis in 3T3-L1 Preadipocytes.

Smaller adipocytes are related to the reversal of metabolic disorders, suggesting that molecules that can act in the adipogenesis pathway are of great interest. The objective of this study was to investigate the effect of Ginkgo biloba extract (GbE) in modulating the differentiation in preadipocytes. 3T3-L1 preadipocytes were differentiated for 7 days into adipocytes without (control group) and with GbE at 1.0 mg/mL. Lipid content and gene expression were analyzed on day 7 (D7) by Oil Red O staining and PCR Array Gene Expression. Western blotting analysis of the key adipogenesis markers was evaluated during the differentiation process at days 3 (D3), 5 (D5), and 7 (D7). GbE increased lipid content and raised the gene expression of the main adipogenesis markers. Key proteins of the differentiation process were modulated by GbE, since C/EBPβ levels were decreased, while C/EBPα levels were increased at D7. Regarding the mature adipocytes’ markers, GbE enhanced the levels of both FABP4 at D5, and perilipin at D3 and D5. In summary, the present findings showed that GbE modulated the adipogenesis pathway suggesting that the treatment could accelerate the preadipocyte maturation, stimulating the expression of mature adipocyte proteins earlier than expected.

Association between liver-type fatty acid-binding protein and hyperuricemia before and after laparoscopic sleeve gastrectomy.

BackgroundLiver-type fatty acid-binding protein (FABP1) contributes to metabolic disorders. However, the relationship between FABP1 and hyperuricemia remains unknown. We aimed to evaluate the correlation between serum FABP1 and hyperuricemia in patients with obesity before and after laparoscopic sleeve gastrectomy (LSG).MethodsWe enrolled 105 patients (47 men and 58 women) with obesity who underwent LSG. They were divided into two groups: normal levels of uric acid (UA) (NUA, n = 44) and high levels of UA (HUA, n = 61) with matching sexes. FABP1 levels and other biochemical parameters were measured at baseline and 3, 6, and 12 months after LSG.ResultsSerum FABP1 levels were significantly higher in the HUA group than in the NUA group (34.76 ± 22.69 ng/mL vs. 25.21 ± 21.68 ng/mL, P=0.024). FABP1 was positively correlated with UA (r=0.390, P=0.002) in the HUA group. The correlation still existed after adjusting for confounding factors. Preoperative FABP1 levels were risk factors for hyperuricemia at baseline. UA and FABP1 levels decreased at 3, 6, and 12 months postoperatively. FABP1 showed a more significant decrease in the HUA group than in the NUA group at 12 months (27.06 ± 10.98 ng/mL vs. 9.54 ± 6.52 ng/mL, P=0.003). Additionally, the change in FABP1 levels positively correlated with changes in UA levels in the HUA group 12 months postoperatively (r=0.512, P=0.011).ConclusionsFABP1 was positively associated with UA and may be a risk factor for hyperuricemia in obesity. FABP1 levels were higher but decreased more after LSG in obese patients with hyperuricemia than in those without hyperuricemia.

A model for predicting acute heart failure in patients with acute myocardial infarction by taking into account energy and adipokine metabolism indicators

Acute heart failure (AHF) is one of the most common complications of acute myocardial infarction (AMI). Currently, adropin, irisin, fatty acid binding protein 4 (FABP 4) and C1q/TNF-binding protein 3 (CTRP 3) are considered to be valid markers of energy homeostasis and the adipokine system in AMI patients. The aim of the study was to predict the development of AHF in AMI patients by taking into account indicators of energy homeostasis and adipokine system using generalized linear mixed model. The study examined 189 patients with acute ST-segment elevation myocardial infarction. Concentrations of adropin, irisin, insulin, FABP4 and CTRP3 were determined by enzyme-linked immunosorbent assay. Fasting capillary blood glucose level was measured by glucoseoxidase method. Insulin resistance (IR) was assessed using homeostasis model assessment of insulin resistance (HOMA-IR). The study identified thrombolysis in myocardial infarction (TIMI) grade before intervention. A generalized linear mixed model was used to develop a method for predicting AHF in AMI patients. The study showed decreased levels of adropin, irisin and CTRP3 and increased levels of FABP4 in AMI patients. A mathematical model for predicting AHF development in AMI patients was proposed. The model consisted of fixed effects, namely, two one-factor indicators (HOMA-IR and systolic blood pressure (BP)), one two-factor indicator (systolic and diastolic BP) and one three-factor indicator (adropin, irisin and CTRP3) and random effects such as four one-factor indicators (FABP4, TIMI Grade Flow, platelets, total cholesterol). The accuracy of predicting the absence of Killip class I AHF was 100%, Killip class II AHF – 0%, Killip class III AHF – 11%, Killip class IV AHF – 82%. It should be noted that systolic BP on day 1 was a strong negative prognostic factor, while HOMA-IR, the combined effect of adropin, irisin and CTRP3, the combined effect of systolic and diastolic BP were positive prognostic factors. Thus, the model showed a very high sensitivity in predicting Killip class IV AHF. The overall accuracy of the model was 89.4%.

Bioinformatics analysis reveals the potential target of rosiglitazone as an antiangiogenic agent for breast cancer therapy

BackgroundSeveral studies have demonstrated the antitumor activity of rosiglitazone (RGZ) in cancer cells, including breast cancer cells. However, the molecular targets of RGZ in the inhibition of angiogenesis in breast cancer cells remain unclear. This study aimed to explore the potential targets of RGZ in inhibiting breast cancer angiogenesis using bioinformatics-based analysis.ResultsVenn diagram analysis revealed 29 TR proteins. KEGG pathway enrichment analysis demonstrated that TR regulated the adipocytokine, AMPK, and PPAR signaling pathways. Oncoprint analysis showed genetic alterations in FABP4 (14%), ADIPOQ (2.9%), PPARG (2.8%), PPARGC1A (1.5%), CD36 (1.7%), and CREBBP (11%) in patients with breast cancer in a TCGA study. The mRNA levels of FABP4, ADIPOQ, PPARG, CD36, and PPARGC1A were significantly lower in patients with breast cancer than in those without breast cancer. Analysis of gene expression using bc-GenExMiner showed that the mRNA levels of FABP, ADIPOQ, PPARG, CD36, PPARGC1A, and CREBBP were significantly lower in basal-like and triple-negative breast cancer (TNBC) cells than in non-basal-like and non-TNBC cells. In general, the protein levels of these genes were low, except for that of CREBBP. Patients with breast cancer who had low mRNA levels of FABP4, ADIPOQ, PPARG, and PPARGC1A had lower overall survival rates than those with high mRNA levels, which was supported by the overall survival related to DNA methylation. Correlation analysis of immune cell infiltration with TR showed a correlation between TR and immune cell infiltration, highlighting the potential of RGZ for immunotherapy.ConclusionThis study explored the potential targets of RGZ as antiangiogenic agents in breast cancer therapy and highlighted FABP4, ADIPOQ, PPARG, PPARGC1A, CD36, and CREBBP as potential targets of RGZ. These findings require further validation to explore the potential of RGZ as an antiangiogenic agent.

Glyoxylase-1 combats dicarbonyl stress and right ventricular dysfunction in rodent pulmonary arterial hypertension.

BackgroundHeightened glycolytic flux is associated with right ventricular (RV) dysfunction in pulmonary arterial hypertension (PAH). Methylglyoxal, a glycolysis byproduct, is a highly reactive dicarbonyl that has toxic effects via non-enzymatic post-translational modifications (protein glycation). Methylglyoxal is degraded by the glyoxylase system, which includes the rate-limiting enzyme glyoxylase-1 (GLO1), to combat dicarbonyl stress. However, the potential consequences of excess protein glycation on RV function are unknown.MethodsBioinformatics analysis of previously identified glycated proteins predicted how protein glycation regulated cardiac biology. Methylglyoxal treatment of H9c2 cardiomyocytes evaluated the consequences of excess protein glycation on mitochondrial respiration. The effects of adeno-associated virus serotype 9-mediated (AAV9) GLO1 expression on RV function in monocrotaline rats were quantified with echocardiography and hemodynamic studies. Immunoblots and immunofluorescence were implemented to probe the effects of AAV-Glo1 on total protein glycation and fatty acid oxidation (FAO) and fatty acid binding protein levels.ResultsIn silico analyses highlighted multiple mitochondrial metabolic pathways may be affected by protein glycation. Exogenous methylglyoxal minimally altered mitochondrial respiration when cells metabolized glucose, however methylglyoxal depressed FAO. AAV9-Glo1 increased RV cardiomyocyte GLO1 expression, reduced total protein glycation, partially restored mitochondrial density, and decreased lipid accumulation. In addition, AAV9-Glo1 increased RV levels of FABP4, a fatty acid binding protein, and hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunits alpha and beta (HADHA and HADHB), the two subunits of the mitochondrial trifunctional protein for FAO. Finally, AAV9-Glo1 blunted RV fibrosis and improved RV systolic and diastolic function.ConclusionExcess protein glycation promotes RV dysfunction in preclinical PAH, potentially through suppression of FAO.

Vasorin contributes to lung injury via FABP4-mediated inflammation.

Lung injury caused by pulmonary inflammation is one of the main manifestations of respiratory diseases. Vasorin (VASN) is a cell-surface glycoprotein encoded by the VASN gene and is expressed in the lungs of developing mouse foetuses. Previous research has revealed that VASN is associated with many diseases. However, its exact function in the lungs and the underlying mechanism remain poorly understood. To investigate the molecular mechanisms involved in lung disease caused by VASN deficiency, a VASN gene knockout (VASN-/-) model was established. The pathological changes in the lungs of VASN-/- mice were similar to those in a lung injury experimental mouse model. We further analysed the transcriptomes of the lungs of VASN-/- mice and wild-type mice. Genes in twenty-four signalling pathways were enriched in the lungs of VASN-/- mice, among which PPAR signalling pathway genes (3 genes, FABP4, Plin1, AdipoQ, were upregulated, while apoA5 was downregulated) were found to be closely related to lung injury. The most significantly changed lung injury-related gene, FABP4, was selected for further verification. The mRNA and protein levels of FABP4 were significantly increased in the lungs of VASN-/- mice, as were the mRNA and protein levels of the inflammatory factors IL-6, TNF-α and IL-1β. We believe that these data provide molecular evidence for the regulatory role of VASN in inflammation in the context of lung injury.

Targeting Fatty Acid-Binding Protein 4 Improves Pathologic Features of Aortic Stenosis.

Aortic stenosis (AS) is a fibrocalcific disease of the aortic valves (AVs). Sex-differences in AS pathophysiology have recently been described. High levels of fatty acid-binding protein 4 (FAPB4) in atherosclerotic plaques have been associated with increased local inflammation, endothelial dysfunction, and plaque vulnerability. FABP4 pharmacological blockade has been shown to be effective for the treatment of atherosclerosis by modulating metabolic and inflammatory pathways. We aimed to analyze the sex-specific expression of FABP4 in AS and its potential role as a therapeutic target. A total of 226 patients (61.5% men) with severe AS undergoing surgical AV replacement were recruited. The FABP4 levels were increased in the AVs of AS patients compared to the control subjects, showing greater expression in the fibrocalcific regions. Male AVs exhibited higher levels of FABP4 compared to females, correlating with markers of inflammation (IL-6, Rantes), apoptosis (Bax, caspase-3, Bcl-2), and calcification (IL-8, BMP-2 and BMP-4). VICs derived from AS patients showed the basal expression of FABP4 in vitro. Osteogenic media induced upregulation of intracellular and secreted FABP4 levels in male VICs after 7 days, along with increased levels of inflammatory, pro-apoptotic, and osteogenic markers. Treatment with BMS309403, a specific inhibitor of FABP4, prevented from all of these changes. Thus, we propose FABP4 as a new sex-specific pharmacological therapeutic target in AS.

PCSK9 and ANGPTL3 levels correlate with hyperlipidemia in HIV-lipoatrophy, are regulated by fasting and are not affected by leptin administered in physiologic or pharmacologic doses

BackgroundMedications leveraging the leptin, PCSK9, ANGPTL3 and FABP4 pathways are being developed for the treatment of insulin resistance and/or lipid disorders. To evaluate whether these pathways are independent from each other, we assessed the levels of PCSK9, ANGPTL3 and FABP4, in normal subjects and subjects exhibiting HIV and highly active antiretroviral therapy (HAART) induced metabolic syndrome with lipoatrophy and hypoleptinemia. Studies were performed at baseline and during food deprivation for three days with either a placebo or leptin administration at physiological replacement doses to correct fasting induced acute hypoleptinemia and in pharmacological doses. MethodsPCSK9, ANGPTL3, FABP4 levels and their correlations to lipoproteins-metabolites were assessed in randomized placebo controlled cross-over studies: a) in 15 normal-weight individuals undergoing three-day admissions in the fed state, in complete fasting with placebo and in complete fasting with leptin treatment in physiologic replacement doses (study 1), b) in 15 individuals day baseline in a fed and three fasting admissions for three days with leptin administered in physiologic, supraphysiologic and pharmacologic doses (study 2), c) in 7 hypoleptinemic men with HIV and HAART-induced lipoatrophy treated with leptin or placebo for two months in the context of a cross over randomized trial (study 3). ResultsCirculating ANGPTL3, PCSK9 and FABP4 were markedly elevated in HIV-lipoatrophy and not affected by leptin treatment. PCSK9 levels correlated with lipids and markers of lipid utilization and lipolysis. ANGPTL3 levels correlated with HDL particles and their lipid composition. FABP4 levels were negatively associated with HDL diameter (HDL-D) and composition. PCSK9 and ANGPTL3 levels decreased during food deprivation by ~65 % and 30 % respectively. Leptin administration at physiologic, supraphysiologic and pharmacologic doses did not affect PCSK9, ANGPTL3 and FABP4 levels. ConclusionsPCSK9, ANGPTL3 and FABP4 levels are associated with markers of lipid metabolism and are higher in HIV-lipoatrophy. PCSK9 and ANGPTL3 but not FABP4 decrease in response to food deprivation. PCSK9 and ANGPTL3 regulation is leptin-independent, suggesting independent pathways for lipid regulation. Thus, combining treatments of leptin with PCSK9 and/or ANGPTL3 inhibitors for metabolic diseases should have additive effects and merit further investigation. Clinical trial informationClinicalTrials.gov no. NCT00140231, NCT00140205, NCT00140244.

MiR-141 Modulates Bone Marrow Mesenchymal Stem Cells (BMSCs) Osteogenic/Adipogenic Differentiation Under Oxidative Stress

BMSCs Osteogenic differentiation is beneficial to the construction of bone tissue engineering. Oxidative stress can affect BMSCs differentiation. MiR-141 regulates BMSCs proliferation. However, MiR-141’s role in BMSCs osteogenic/adipogenic differentiation under oxidative stress is unclear. Mice BMSCs were assigned into control group; oxidative stress group; and si-MiR-141 group followed by detecting miR-141 level. After 14 days of osteogenesis or adipogenesis induction, RUNX2, OPN and FABP4 mRNA level was analyzed together with analysis of ROS and SOD content, ALP activity and TGFβ/smad signaling protein level by Western blot. Under oxidative stress, MiR-141 was significantly upregulated and RUNX2 and OPN level was decreased, along with increased ROS content and FABP4 level, reduced SOD and ALP activity and expression of TGFβ1 and smad2 (P < 0.05). Transfection of MiR-141 siRNA into BMSCs under oxidative stress down-regulated MiR-141, significantly upregulated RUNX2 and OPN, reduced ROS, elevated SOD activity, downregulated FABP4, and increased ALP activity and TGFβ1 and smad2 expression (P < 0.05). In conclusion, MiR-141 expression is increased in BMSCs under oxidative stress. Down-regulating MiR-141 improves the redox imbalance through TGFβ/smad signaling pathway, promotes osteogenic differentiation of BMSCs and inhibits differentiation to adipocytes.

The Correlations of Plasma Liver-Type Fatty Acid-Binding Protein with Amyloid-β and Tau Levels in Patients with Alzheimer's Disease.

The dysregulation of lipid metabolism plays an important role in the pathogenesis of Alzheimer's disease (AD). Liver-type fatty acid-binding protein (L-FABP, also known as FABP1) is critical for fatty acid transport and may be involved in AD. To investigate whether the FABP1 level is altered in patients with AD, and its associations with levels of amyloid-β (Aβ) and tau in the plasma and cerebrospinal fluid (CSF). A cross-sectional study was conducted in a Chinese cohort consisting of 39 cognitively normal controls and 47 patients with AD. The levels of FABP1 in plasma, and Aβ and tau in CSF, were measured by enzyme-linked immunosorbent assay (ELISA). A single-molecule array (SIMOA) was used to detect plasma Aβ levels. The level of plasma FABP1 was significantly elevated in the AD group (p = 0.0109). Further analysis showed a positive correlation of FABP1 with CSF total tau (t-tau) and phosphorylated tau (p-tau) levels. Besides, plasma FABP1/Aβ42 (AUC = 0.6794, p = 0.0071) and FABP1/t-tau (AUC = 0.7168, p = 0.0011) showed fair diagnostic efficacy for AD. When combined with other common AD biomarkers including plasma Aβ42, Aβ40, and t-tau, both FABP1/Aβ42 and FABP1/t-tau showed better diagnostic efficacy than using these biomarkers alone. Among all AUC analyses, the combination of plasma FABP1/t-tau and Aβ42 had the highest diagnostic value (AUC = 0.8075, p < 0.0001). These findings indicate that FABP1 may play a role in AD pathogenesis and be worthy of further investigation in the future.

MiR-375 is cold exposure sensitive and drives thermogenesis in visceral adipose tissue derived stem cells

Activation of brown adipose tissue may increase energy expenditure by non-shivering thermogenesis. Cold exposure is one of the options to activate brown adipocytes. To link changes in energy metabolism with microRNA expression (miRNAs), we analyzed 158 miRNAs in serum of 169 healthy individuals before and after cold exposure. Validating the results of a miRNA array, a significant down-regulation of miR-375 after cold exposure (P < 0.0001) was detected. These changes went along with a significant negative correlation between miR-375 and visceral adipose tissue (VAT) mass (P < 0.0001), implicating a specific function of miR-375 in this depot. Significantly higher expression levels of miR-375 were found in VAT in comparison to subcutaneous fat (SAT). Using in silico prediction, we identified putative miR-375 target genes involved in the thermogenesis pathway. Cold-stimulation of subcutaneous and visceral pre-adipocytes (PACs) led to significantly higher expression levels of FABP4, FGF21, PPARGC1A and PRDM16 in VC-PACs. Analyzing miR-375 knock down and cold stimulated VC-PACs revealed a significant up-regulation of thermogenesis associated genes PPARGC1A, ELOVL3 and PRDM16. In summary, our findings identified miR-375 as a potential adipogenic and thermogenesis-associated miRNA exclusively acting in visceral adipose tissue.

Long noncoding RNA ZBTB40-IT1 regulates bone mass by directing the differentiation of human bone marrow mesenchymal stromal cells via the microRNA-514a-3p/FOXO4 axis.

This study intended to clarify the mechanism of long noncoding RNA ZBTB40-IT1 in directing human bone marrow-derived mesenchymal stromal cell (hBMSC) differentiation. hBMSCs underwent osteogenic and adipogenic induction, and an osteoporosis mouse model was established via ovariectomy (OVX). Gain- and loss-of-function approaches were utilized in hBMSCs and mice to investigate the function of ZBTB40-IT1, microRNA (miR)-514a-3p, and forkhead box O4 (FOXO4). Dual-luciferase reporter and RNA pulldown assays were applied to evaluate the binding of miR-514a-3p to ZBTB40-IT1 or FOXO4. The femur of the OVX mice had upregulated ZBTB40-IT1 and FOXO4 expression and downregulated miR-514a-3p expression. The bone mass was increased in OVX mice through ZBTB40-IT1 or FOXO4 knockdown. ZBTB40-IT1 and FOXO4 were downregulated, whereas miR-514a-3p was upregulated in osteogenesis-induced hBMSCs, which was the opposite in adipogenesis-induced hBMSCs. ZBTB40-IT1 or FOXO4 knockdown or miR-514a-3p overexpression increased ARS/ALP absorbance and RUNX2 and OCN levels but decreased fat density and PPARγ and FABP4 levels in hBMSCs. Mechanistically, ZBTB40-IT1 elevated FOXO4 expression by binding to miR-514a-3p. miR-514a-3p inhibition annulled the effects of ZBTB40-IT1 downregulation on hBMSC osteogenesis and adipogenesis, and FOXO4 overexpression abolished the impacts of miR-514a-3p upregulation on hBMSC osteogenesis and adipogenesis. Conclusively, ZBTB40-IT1 inhibition promotes the osteogenic differentiation of hBMSCs via the miR-514a-3p/FOXO4 axis, thereby increasing bone mass.

1442-P: Association of Elevated Serum FABP1 with Hyperuricemia in Patients with Obesity and the Alteration after Sleeve Gastrectomy

Aims: FABP1’s relationship with obesity-related hyperuricemia remains unknown. We aimed to evaluate FABP1-level changes in patients with obesity-related hyperuricemia and changes after laparoscopic sleeve gastrectomy (LSG) . Materials and Methods: Participants were categorized according to uric acid (UA) level: normal UA group (NUA, men≤420 μmol/L, women≤360 μmol/L) and high UA group (HUA, men&amp;gt;420 μmol/L, women&amp;gt;360 μmol/L) . The cross-sectional analysis included 123 non-obese individuals (NUA, n=90; HUA, n =33) and 76 patients with obesity (NUA, n =31; HUA, n =45) who underwent LSG. FABP1 levels were measured at baseline and 3, 6, and 12 months post-LSG. Results: In non-obese individuals, FABP1 did not differ statistically between the NUA and HUA groups (15.52±15.62 ng/mL vs. 18.44±11.47 ng/mL, P=0.330) . However, in patients with obesity, FABP1 was positively correlated with UA and higher in the HUA than in the NUA group (32.47±22.35 ng/mL vs. 22.84±14.54 ng/mL, P&amp;lt;0.05) . Multiple linear regression found a positive correlation between FABP1 and UA (R2=0.101, β=0.317, 95% CI=0.020-0.110, P&amp;lt;0.01) , and binomial logistic regression found that FABP1 could predict HUA in patients with obesity (OR=1.031, 95% CI=1.002-1.061, P&amp;lt;0.05) . UA and FABP1 levels, whether in the NUA or HUA group, decreased at 3, 6, and 12 months postoperatively. But FABP1 decreased faster in the HUA than NUA group, and there was a statistical difference at 12 months. Conclusions: FABP1 increased in obesity-related hyperuricemia in contrast to only obesity. And FABP1 decreased faster in the HUA than in the NUA group among obesity postoperatively. Key words: FABP1, Obesity, Hyperuricemia, Laparoscopic sleeve gastrectomy Disclosure S.Qu: n/a. Y.Hui: None. Funding NSFC 81700752，2021SYPDRC059

PET/MRI-Evaluated Activation of Brown Adipose Tissue via Cold Exposure Impacts Lipid Metabolism.

Although brown adipose tissue (BAT) is considered to play a protective role against obesity and type 2 diabetes, the mechanisms of its activation and associations with clinical parameters are not well described. Male adults underwent a 2 h cold exposure (CE) to activate BAT and, based on the results of PET/MRI performed after the CE, were divided into BAT(+) and BAT(−) groups. During the CE procedure, blood samples were collected and alterations in plasma metabolome in both groups were investigated using LC-MS. Additionally, associations between clinical factors and BAT were examined. Moreover, levels of glucose, insulin, leptin, TNF-α, FGF21, and FABP4 were assessed in serum samples. In the BAT(+) group, levels of LPC(17:0), LPE(20:4), LPE(22:4), LPE(22:6), DHA, linoleic acid, and oleic acid increased during CE, whereas levels of sphinganine-phosphate and sphingosine-1-phosphate decreased. Levels of LPE(O-18:0), 9-HpODE, and oleic acid were elevated, while the level of LPE(20:5) was reduced in BAT(+) compared to BAT(−) subjects. AUCs of LPC(18:2), LPC(O-18:2)/LPC(P-18:1), and SM(d32:2) negatively correlated with BAT. In the BAT(+) group, the concentration of FABP4 during and after CE was decreased compared to the basal level. No alterations were observed in the BAT(−) group. In conclusion, using untargeted metabolomics, we proved that the plasma metabolome is affected by cold-induced BAT activation.

MiR-218-5p Affects Subcutaneous Adipogenesis by Targeting ACSL1, a Novel Candidate for Pig Fat Deposition

As a centre enzyme in fatty acid activation, acyl-CoA synthetase long-chain family member 1 (ACSL1) plays an important role in body lipid homeostasis. However, the functions of ACSL1 in the subcutaneous adipogenesis of pigs are largely unknown. In the present study, we found that the expression of ACSL1 significantly increased during the process of porcine preadipocyte differentiation. Moreover, silencing of ACSL1 in preadipocytes decreased levels of triglyceride and adipogenic-related markers, including FABP4, APOE, and FASN (p < 0.01), and simultaneously increased levels of lipolytic-related markers, such as ATGL and HSL (p < 0.05). Conversely, overexpression of ACSL1 in preadipocytes increased levels of triglyceride and FABP4, APOE, and FASN (p < 0.01), and reduced levels of ATGL and HSL (p < 0.05). Luciferase reporter assays revealed that ACSL1 is a target of miR-218-5p, which can reduce the mRNA and protein levels of ACSL1 by directly binding the 3′ untranslated region of ACSL1. Furthermore, miR-218-5p has an inhibition role in porcine preadipocyte differentiation by suppressing ACSL1 expression. Taken together, these data provide insights into the mechanism of the miR-218-5p/ACSL1 axis in regulating subcutaneous fat deposition of pigs.

Downregulation of PPARα mediates FABP1 expression, contributing to IgA nephropathy by stimulating ferroptosis in human mesangial cells.

Immunoglobulin A nephropathy (IgAN) is the commonest primary glomerulonephritis, and a major cause of end-stage renal disease; however, its pathogenesis requires elucidation. Here, a hub gene, FABP1, and signaling pathway, PPARα, were selected as key in IgAN pathogenesis by combined weighted gene correlation network analysis of clinical traits and identification of differentially expressed genes from three datasets. FABP1 and PPARα levels were lower in IgAN than control kidney, and linearly positively correlated with one another, while FABP1 levels were negatively correlated with urinary albumin-to-creatinine ratio, and GPX4 levels were significantly decreased in IgAN. In human mesangial cells (HMCs), PPARα and FABP1 levels were significantly decreased after Gd-IgA1 stimulation and mitochondria appeared structurally damaged, while reactive oxygen species (ROS) and malondialdehyde (MDA) were significantly increased, and glutathione and GPX4 decreased, relative to controls. GPX4 levels were decreased, and those of ACSL4 increased on siPPARα and siFABP1 siRNA treatment. In PPARα lentivirus-transfected HMCs stimulated by Gd-IgA1, ROS, MDA, and ACSL4 were decreased; glutathione and GPX4, and immunofluorescence colocalization of PPARα and GPX4, increased; and damaged mitochondria reduced. Hence, PPARα pathway downregulation can reduce FABP1 expression, affecting GPX4 and ACSL4 levels, causing HMC ferroptosis, and contributing to IgAN pathogenesis.

SIRT5 promotes non-small cell lung cancer progression by reducing FABP4 acetylation level.

This study evaluates the role of SIRT5 in non-small cell lung cancer (NSCLC) progression and explores the underlying mechanism. The expression and correlation of SIRT5 and FABP4 in lung cancer were analyzed by the GEPIA database. The expression levels of SIRT5 and FABP4 in NSCLC cells were measured by qRT-PCR and western blot. The effect of SIRT5 and FABP4 on NSCLC cell development was determined. The interaction between SIRT5 and FABP4 was analyzed by co-immunoprecipitation (Co-IP). Tumor mass and volume were measured in nude mice to study the effect on the growth of NSCLC transplanted tumors. GEPIA database analysis showed that SIRT5 was highly expressed, while FABP4 was lowly expressed in lung cancer, which was consistent with the detection results of SIRT5 and FABP4 expressions in NSCLC cell lines. The expression of SIRT5 was negatively correlated with FABP4. Transfection of sh-SIRT5 in NSCLC cells led to a decrease in NSCLC cell malignancy, which was counteracted by sh-FABP4 transfection. Western blot and Co-IP showed that SIRT5 reduced FABP4 expression by inducting the deacetylation of FABP4. Nude mice in the sh-SIRT5 + sh-FABP4 group had significantly reduced tumor mass and volume compared with those in the sh-FABP4 group, while the tumor mass and volume in the sh-SIRT5 + sh-FABP4 group were increased in comparison to those in the sh-SIRT5 group. To conclude, collected evidence showed that SIRT5 promoted NSCLC cell development by reducing FABP4 acetylation level.

LEFT VENTRICLE REMODELING IN PATIENTS WITH POSTINFARCTION CARDIOSCLEROSIS AND OBESITY, TAKING INTO ACCOUNT FABP 4 AND CTRP 3 LEVELS

The objective – to study the structural-functional condition of the left ventriclemyocardium (LV) in patients with postinfarction cardiosclerosis and surplus body weighttaking into account the levels of adipokines FABP4 and CTR3.Material and methods. The study involved 189 patients. The first group consisted of60 patients with postinfarction cardiosclerosis, the second group included 68 patientswith postinfarction cardiosclerosis and excess body weight (EBW), the third groupcomprised 61 patients with postinfarction cardiosclerosis and obesity. The content ofFABP 4 and CTRP 3 was determined by enzyme-linked immunosorbent assay. Statisticalprocessing of the survey results was performed using the licensed software package“IBM SPPS Statistics 27.0”. According to the sample size and distribution of indicators,the parametric Student’s test was used. Evaluation of the significance of the differencebetween the means of multiple comparisons for quantitative traits with normaldistribution using Bonferroni correction was performed by one-way analysis of variance(ANOVA).The mean and the error of the mean were determinedThe correlations of theindicators were determined using the Pearson correlation coefficient (r). At a value ofp˂0.05, the difference was considered significant.Results. Patients with post-infarction cardiosclerosis and obesity in comparison withpatients without excess body weight were found to have an increase in end-systolicvolume (ESV), end-diastolic volume, end-diastolic size (EDS), end-systolic size (ESS),stroke volume, thickness of interventricular septum, thickness of the posterior wallof the left ventricle, size of the left atrium, mass of the left ventricular myocardium,LVMMI. A direct relationship between FABP 4 and ESS, ESV, LVMMI1in patients withpostinfarction cardiosclerosis and obesity was determined. There was a significantinverse correlation between CTRP 3 and EDS, ESS, ESV, LVMMI1 in patients withpostinfarction cardiosclerosisand obesity.Conclusions. The study showed that in patients with postinfarction cardiosclerosi 34sand obesity there was an increase in echocardiographic parameters. The influence ofFABP 4 and CTRP 3 content on the structural and functional state of the left ventricularmyocardium was determined.