Fatty acid-binding protein 4 (FABP4), a fatty acid transporter that coordinates lipid metabolism, is reported to exert a tumorigenic role in certain cancers. We investigated the effects of FABP4 in the carcinogenesis of thyroid cancer. Bioinformatics data about FABP4 in thyroid cancer were collected from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Sixteen paired papillary thyroid cancer (PTC) tissues from Taipei Medical University (TMU) were gathered, and commercial thyroid cancer complementary (c)DNA and tissue arrays were purchased to measure FABP4 messenger (m)RNA and protein levels. By analyzing data from the GEO and TCGA, we showed that FABP4 mRNA was reduced in PTC and follicular thyroid carcinoma (FTC). In addition, a lower FABP4 mRNA level in PTC was associated with poor clinical parameters and outcomes in the TCGA database. Moreover, FABP4 transcripts and proteins were downregulated in PTC and FTC, and its mRNA expression was associated with PTC staging in clinical specimens. In the TCGA database and TMU cohort, FABP4 mRNA levels were associated with thyroglobulin (r = 0.511 and r = 0.656, respectively), thyroid peroxidase (r = 0.612 and r = 0.909, respectively), and sodium iodide symporter (r = 0.485 and r = 0.637, respectively) transcripts. In conclusion, FABP4 mRNA and protein levels were reduced in PTC and FTC, and may be used as a potential indicator for thyroid cancer evolution in clinical settings. Further, well-designed research to dissect the molecular mechanism of FABP4 in modulating thyroid carcinogenesis is needed.

The increasing side effects of traditional medications used to treat type II diabetes have made research into the development of safer and more effective natural medications necessary. ACT001, a derivative of parthenolide, has been shown to have good anti-inflammatory and antitumor effects; however, its role in diabetes is unclear. The short-chain fatty acid propionate is a common food preservative that has been found to cause disturbances in glucose metabolism in mice and humans. This study aimed to investigate whether sodium propionate could aggravate insulin resistance in obese mice and cause diabetes and to study the alleviative effects and potential mechanisms of action of ACT001 on insulin resistance in diabetic mice. Type II diabetic mice were adminietered sodium propionate combined with a high-fat diet (HFD + propionate) by gavage daily for four weeks. Biochemical analysis showed that ACT001 significantly affected blood glucose concentration in diabetic mice, mainly by downregulating the expression of phosphoenolpyruvate carboxykinase 2 and glucose-6-phosphatase. Meanwhile, the level of fatty acid-binding protein 4 in the liver was significantly decreased. ACT001 has a protective effect on the liver and adipose tissue of mice. In addition, the results of the running wheel experiment indicated that ACT001 alleviated the circadian rhythm disorder caused by insulin resistance to a certain extent. This study revealed the potential mechanism by which ACT001 alleviates insulin resistance and provides ideas for developing natural antidiabetic drugs.

Prolonged activation of microglia leads to excessive release of proinflammatory mediators, which are detrimental to brain health. Therefore, there are significant efforts to identify pathways mediating microglial activation. Recent studies have demonstrated that fatty acid-binding protein 4 (FABP4), a lipid binding protein, is a critical player in macrophage-mediated inflammation. Given that we have previously identified FABP4 in microglia, the aim of this study was to assess whether FABP4 activity contributed to inflammation, metabolism and immune function (i.e. immunometabolism) in immortalised mouse microglia (BV-2 cells) using the proinflammatory stimulus lipopolysaccharide (LPS) to induce general microglial activation. Microglial FABP4 expression was significantly increased following exposure to LPS, an outcome associated with a significant increase in microglial proliferation rate. LPS-stimulated BV-2 microglia demonstrated a significant increase in the production of reactive oxygen species (ROS) and tumour necrosis factor-alpha (TNF-α), phosphorylation of c-Jun N-terminal kinase (JNK), increased expression of Toll-like receptor 4 (TLR4), and reduced expression of uncoupling protein 2 (UCP2), all of which were reversed following FABP4 genetic silencing and chemical inhibition with BMS309403. The oxidation rate of 3H-oleic acid and microglial uptake of 3H-2-deoxy-D-glucose were modulated with LPS activation, processes which were restored with genetic and chemical inhibition of FABP4. This is the first study to report on the critical role of FABP4 in mediating the deleterious effects of LPS on microglial immunometabolism, suggesting that FABP4 may present as a novel therapeutic target to alleviate microglia-mediated neuroinflammation, a commonly reported factor in multiple neurodegenerative diseases.

Accumulating evidence has shown that medicinal plants have been exploited for treatment purposes since time immemorial. Thus, this study investigated the mitigating potentials of the ligands; n-hexadecanoic acid, 9-octadecenoic acid and octadecanoic acid from Copaifera salikounda seed pond extract reported to have antidiabetic potentials in our previous study using computational techniques. Fatty acid-binding protein 4 (FABP4) and peroxisome proliferator-activated receptor alpha (PPARα) were identified as potential receptors. Both molecular docking and Estimated ΔGbind revealed that each ligand exhibited high binding affinity to the respective proteins; this is quite sufficient to be termed favourable. A critical examination of the type and the nature of binding interactions and energy contributions have identified Arg106, Arg126 and Tyr128 in FABP4 and Gln277, Ser280, Tyr314, His440 and Tyr464 in PPARα as consistently being responsible for the binding interactions and stabilizations of each ligand to the individual proteins. The establishment of hydrogen bonding type of interaction and activity between the carboxylic acid moieties of these ligands and these crucial/unique residues goes further to buttress our assertion. A general study of the conformational state of these protein via RMSF and PCA plots goes further validate the observed structural trends wherein the presence of ligands induced seemly structural rigidity. In depth structural stability investigations went further to reveal that the 3D structures of these protein didn\'t deviate from it known native conformational stable state when bound with these ligands. Our findings indicate that the ligands have considerable inhibitory action against FABP4 and PPARα corroborating the reported antidiabetic potential of the extract.

Adipokines are signaling molecules involved in the integration of metabolism. Changes in their concentrations were observed in obesity, metabolic syndrome, diabetes mellitus and cardiovascular diseases, as well as endocrine disorders. Cushing\'s syndrome is associated with metabolic dysregulation, but the significance of adipokines in this entity and related complications is largely unknown. The aim of our study was to determine the concentrations of adipokines: fetuin A, fatty acid binding protein 4 (FABP4) and retinol binding protein 4 (RBP4) in Cushing\'s syndrome and to assess their relation to established cardiovascular and diabetes risk markers.
We examined 21 subjects with Cushing\'s syndrome and 24 healthy controls in a cross-sectional manner. Venous blood samples were analysed for adipokines, cortisol, adrenocorticotrophin, glucose, insulin, glycated haemoglobin (HbA1c), triglycerides, cholesterol fractions, thyrotropin and free thyroid hormones concentrations. Patients\' body mass index (BMI) was evaluated, homeostatic model assessment-insulin resistance and Systematic Coronary Risk Evaluation (SCORE) were calculated.
We found that the concentration of fetuin A was lower, while FABP4 and RBP4 concentrations were higher in Cushing\'s syndrome compared to controls [156.4 ± 60.0 µg/ml vs 260.7 ± 49.6 µg/ml; 79.8 (35.2-156.1) ng/ml vs 27.9 (17.1-36.7) ng/ml and 34 (30-37.7) mg/l vs 25.8 (23.6-27.7) mg/l, respectively]. Fetuin A correlated inversely, while FABP4 and RBP4 positively, with the concentrations of urinary free cortisol and adrenocorticotrophin. Fetuin A was positively related to LDL-cholesterol, and negatively to SCORE and HbA1c. FABP4 was associated positively with BMI, HbA1c and triglycerides, while RBP4 correlated positively with triglycerides and systolic blood pressure.
Adipokines\' concentrations change in hypercortisolism. Further research is needed to ascertain whether adipokines are involved in the development of metabolic complications accompanying Cushing\'s syndrome or secondarily reflect metabolic dysregulation.

UNASSIGNED: To explore the relationship between the level of fatty acid-binding protein 4 (FABP4) and reversion from prediabetes to normal glucose tolerance (NGT).
UNASSIGNED: A two-year retrospective cohort study was conducted on 398 participants with complete information. These 398 participants were divided into an NGT group and an abnormal glucose metabolism (AGM) group after 2 years of follow-up. The baseline level of FABP4 was determined, and the role of FABP4 in predicting reversion from prediabetes to NGT was investigated using an unconditional logistic regression model.
UNASSIGNED: Over the two-year follow-up period, 37.4% (149/398) of the participants reverted from prediabetes to NGT. The participants with AGM had a higher baseline level of FABP4 than those with NGT. The baseline level of FABP4 was significantly negatively correlated with reversion from prediabetes to NGT. After adjusting for age, sex, body mass index and waist-to-hip ratio, the level of fasting blood glucose (FBG) [odds ratio (OR) 0.336, 95% confidence interval (CI) (0.196-0.576)], 2-h post-challenge blood glucose (2hBG) [OR 0.697, 95% CI (0.581-0.837)], and FABP4 [OR 0.960, 95% CI (0.928-0.993)] at baseline were significant independent predictors of reversion from prediabetes to NGT. The area under the curve (AUC) value of the receiver operating characteristic curve for FABP4 was 0.605 (95% CI: 0.546-0.665), and the AUC for FABP4 combined with FBG and 2hBG was 0.716 (95% CI: 0.663-0.769).
UNASSIGNED: A higher baseline level of FABP4 was positively correlated with an adverse profile of diabetes risk factors and negatively correlated with reversion from prediabetes to NGT. FABP4, FBG and 2hBG were predictors of reversion from prediabetes to NGT.

Signalling between the tissues integrating synthesis, transformation and utilization of energy substrates and their regulatory hormonal axes play a substantial role in the development of metabolic disorders. Interactions between cytokines, particularly liver derived hepatokines and adipokines, secreted from adipose tissue, constitute one of major areas of current research devoted to metabolic dysregulation. The thyroid exerts crucial influence on the maintenance of basal metabolic rate, thermogenesis, carbohydrate and lipid metabolism, while its dysfunction promotes the development of metabolic disorders. In this review, we discuss the interplay between three adipokines: fatty acid binding protein type 4, fetuin-A, retinol binding protein type 4 and thyroid hormones, that shed a new light onto mechanisms underlying atherosclerosis, cardiovascular complications, obesity, insulin resistance and diabetes accompanying thyroid dysfunction. Furthermore, we summarize clinical findings on those cytokines in the course of thyroid disorders.

Background: Fatty acid-binding protein 4 (FABP4) is an adipokine that plays a causative role in obesity and diabetes. In a stratified cross-sectional study with adolescents, we explored whether changes in FABP4 are already present in lean adolescents, provided they display elements of insulin resistance (IR). Methods: Adolescents were divided in four groups according to body mass index and homeostasis model assessment-IR. Results: In metabolically unhealthy lean (MUL) adolescents (MUL, lean with IR), FABP4 was 33% higher than in healthy counterparts (metabolically healthy lean [MHL]). Obese adolescents without IR (metabolically healthy obesity [MHO]) had 50% higher levels of FABP4 than their lean counterparts (MHL), while levels of FABP4 in obese adolescents with IR (metabolically unhealthy obese [MUO]) were 220% higher than those of MUL adolescents. The differences were significant at least with P < 0.005. MUO > MHO > MUL. Our data demonstrate that the known FABP4 defect in adults with obesity also occurs in youth and even in lean adolescents, suggesting an early association between impaired glucose metabolism and FABP4 irrespective of body weight. FABP4 was more sensitive in discerning each of our 4 subgroups than either adiponectin or leptin. Moreover, evidence for a putative early adiponectin resistance in MUL suggests a combined defect in these adolescents that call for early detection and prevention of the metabolic disturbance that should stay away from concentrating only in subjects with obesity. Conclusions: Our data may serve to draw the considerable attention that is currently paid to FABP4 to the adolescent population, irrespective of the presence of obesity. Further studies with larger cohorts and analyses of visceral and liver fat are warranted.

Natural flavonoid pectolinarigenin (PEC) was reported to alleviate tubulointerstitial fibrosis of unilateral ureteral obstruction (UUO) mice in our previous study. To further investigate nephroprotective effects of PEC in hyperuricemic nephropathy (HN), adenine and potassium oxonate induced HN mice and uric acid-treated mouse kidney epithelial (TCMK-1) cells were employed in the study. As a result, PEC significantly lowered serum uric acid level and restored hyperuricemia-related kidney injury in HN mice. Meanwhile, PEC alleviated inflammation, fibrosis, and reduced adipokine FABP4 content in the kidneys of HN mice and uric acid-treated TCMK-1 cells. Mechanistically, PEC inhibited the TGF-β1 expression as well as the phosphorylation of transcription factor SMAD3 and STAT3 to regulate the corresponding inflammatory and fibrotic gene expression in kidney tissues. In conclusion, our results suggested that PEC could inhibit the activation of SMAD3 and STAT3 signaling to suppress inflammation and fibrosis, and thereby alleviate HN in mice.

OBJECTIVE: Peritoneal endometriosis is a chronic inflammatory disease particularly associated with macrophages. Of note, adipose tissues with fibrotic changes in the context of peritoneal endometriotic lesions are often observed during surgery. However, the characteristics of fibrotic adipose tissues in endometriosis are still unknown. In this study, we investigated the inflammatory status of retroperitoneal adipose tissues adjacent to pelvic endometriotic lesions.
METHODS: Thirty-two patients who underwent surgical treatment were assigned to either the endometriosis (n = 16) or the control (n = 16) groups. Retroperitoneal adipose tissues around the uterus were collected from patients in both groups. Fibrosis was evaluated via Masson\'s trichrome staining. Macrophage infiltration, the expression of fatty acid-binding protein 4 (FABP4), and angiogenesis in the retroperitoneal adipose tissues were evaluated via immunohistochemistry. The mRNA expression levels of cytokines was also evaluated in the adipose tissues using real-time PCR.
RESULTS: There was more fibrosis and angiogenesis in the adipose tissues adjacent to the endometriotic lesions with a significantly higher level of infiltration of macrophages and a predominance of the M1 type in the endometriosis group compared to the control group. In addition, FABP4 positivity in the adipose tissues of the peritoneum was significantly higher in the endometriosis group versus the control group. Moreover, the mRNA expression levels of FABP4, VEGF, and proinflammatory cytokines were also significantly higher in the endometriosis group.
CONCLUSIONS: Altogether, our results showed that the adipose tissue adjacent to endometriotic lesions are inflamed with fibrosis and angiogenesis.