Mendelian randomization analyses reveal no genetic causal effects of major adipokines on systemic lupus erythematosus.

Epidemiological studies have shown that the levels of serum adipokine such as leptin and resistin are associated with the risk of developing systemic lupus erythematosus (SLE). Nevertheless, whether either leptin or resistin has causal impacts on the risk of SLE is still unknown. In this study, two-sample univariable MR analyses and multivariable MR analysis were performed to explore the causal relationships between adipokines and SLE. Additionally, the potential causal effects of SLE on major adipokines were evaluated using reverse MR analyses. The results of inverse-variance weighted (IVW), weighted median, weighted mode and MR‒Egger methods concordantly supported that major adipokines have no causal effects on the risk of SLE. In the multivariable MR IVW analysis with leptin and resistin as covariates, neither leptin (odds ratio (OR) = 3.093, P = 0.067) nor resistin (OR = 0.477, P = 0.311) was identified as an independent risk factor for SLE, which is in line with the univariable MR results. In conclusion, our analyses revealed no evidence to support that these three major adipokines are risk factors for SLE.

Mediterranean diet effects on vascular health and serum levels of adipokines and ceramides.

BACKGROUND: A randomized clinical trial to evaluate the effect of a Mediterranean-style diet on vascular health indices such as endothelial function indices, serum lipid and ceramide plasma and some adipokine serum levels. We recruited all consecutive patients at high risk of cardiovascular diseases admitted to the Internal Medicine and Stroke Care ward at the University Hospital of Palermo between September 2017 and December 2020. MATERIALS AND METHODS: The enrolled subjects, after the evaluation of the degree of adherence to a dietary regimen of the Mediterranean-style diet, were randomised to a Mediterranean Diet (group A) assessing the adherence to a Mediterranean-style diet at each follow up visit (every three months) for the entire duration of the study (twelve months) and to a Low-fat diet (group B) with a dietary "counselling" starting every three months for the entire duration of the study (twelve months).The aims of the study were to evaluate: the effects of adherence to Mediterranean Diet on some surrogate markers of vascular damage, such as endothelial function measured by means of the reactive hyperaemia index (RHI) and augmentation index (AIX), at the 6-(T1) and 12-month (T2) follow-ups; the effects of adherence to Mediterranean Diet on the lipidaemic profile and on serum levels of ceramides at T1 and T2 follow-ups; the effects of adherence to Mediterranean Diet on serum levels of visfatin, adiponectin and resistin at the 6- and 12-month follow-ups. RESULTS: A total of 101 patients were randomised to a Mediterranean Diet style and 52 control subjects were randomised to a low-fat diet with a dietary "counselling". At the six-month follow-up (T1), subjects in the Mediterranean Diet group showed significantly lower mean serum total cholesterol levels, and significantly higher increase in reactive hyperaemia index (RHI) values compared to the low-fat diet group. Patients in the Mediterranean Diet group also showed lower serum levels of resistin and visfatin at the six-month follow-up compared to the control group, as well as higher values ​​of adiponectin, lower values of C24:0, higher values of C22:0 and higher values of the C24:0/C16:0 ratio. At the twelve-month follow-up (T2), subjects in the Mediterranean Diet group showed lower serum total cholesterol levels and lower serum LDL cholesterol levels than those in the control group. At the twelve-month follow-up, we also observed a further significant increase in the mean RHI in the Mediterranean Diet group, lower serum levels of resistin and visfatin, lower values of C24:0 and of C:18:0,and higher values of the C24:0/C16:0 ratio. DISCUSSION: The findings of our current study offer a further possible explanation with regard to the beneficial effects of a higher degree of adherence to a Mediterranean-style diet on multiple cardiovascular risk factors and the underlying mechanisms of atherosclerosis. Moreover, these findings provide an additional plausible interpretation of the results from observational and cohort studies linking high adherence to a Mediterranean-style diet with lower total mortality and a decrease in cardiovascular events and cardiovascular mortality. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04873167. https://classic.clinicaltrials.gov/ct2/show/NCT04873167.

The Beneficial Effects of Nordic Walking Training Combined with Time-Restricted Eating 14/24 in Women with Abnormal Body Composition Depend on the Application Period.

The aim of the study was to assess the impact of two lengths of Nordic walking (NW) training interventions combined with time-restricted eating (TRE) on improving body-composition parameters, lipid profiles, and levels of selected adipokines in women with elevated body mass. Overweight and obese women (n = 55, age: 21-85) were recruited. Four groups were selected: 6 weeks (SG6, n = 13) and 12 weeks intervention (SG12, n = 13); and two control groups: CON6 (n = 13) and CON12 (n = 13). The training sessions took place three times a week (60 min each) and were conducted outdoors under the supervision of a professional coach. The training intensity was determined individually. The extended NW program combined with TRE induced a significant weight reduction in SG12 by 1.96 kg (p = 0.010) and fat tissue by 1.64 kg (p = 0.05). The proposed interventions did not affect LBM, TBW [kg], VFA, and lipid profile. The LDL/HDL ratio changed with a small size effect. The leptin concentration differed between groups (p = 0.006), but not over time. For resistin, the differentiating factor was time (p = 0.019), with lower results observed after the intervention. The change in leptin concentration was negatively correlated with its baseline concentration (p = 0.025). Extended to 12 weeks, this intervention allows for an improvement in body composition. Neither 6 nor 12 weeks of training and fasting affected the lipoprotein profile. It is, therefore, indicated to recommend prolonged training protocols and to inform patients that beneficial effects will be seen only after prolonged use of training and time-restricted eating.

Gestational Diabetes Mellitus and Colostral Appetite-Regulating Adipokines.

Gestational diabetes mellitus (GDM) is a complex metabolic disorder that has short- and long-term effects on maternal and offspring health. This study aimed to assess the impact of maternal hyperglycemia severity, classified as GDM-G1 (diet treatment) and GDM-G2 (insulin treatment) on colostral appetite-regulating molecules. Colostrum samples were collected from hyperglycemic (N = 30) and normoglycemic (N = 21) mothers, and the concentrations of milk hormones were determined by immunoenzymatic assay. A difference was found for milk ghrelin, but not for molecules such as adiponectin, leptin, resistin, or IGF-I levels, in relation to maternal hyperglycemia. The colostral ghrelin in the GDM-G1 cohort (0.21 ng/mL) was significantly lower than for GDM-G2 (0.38 ng/mL) and non-GDM groups (0.36 ng/mL). However, colostral resistin was higher, but not significantly, for GDM-G1 (13.33 ng/mL) and GDM-G2 (12.81 ng/mL) cohorts than for normoglycemic mothers (7.89 ng/mL). The lack of difference in relation to hyperglycemia for milk leptin, adiponectin, leptin-adiponectin ratio, resistin, and IGF-I levels might be the outcome of effective treatment of GDM during pregnancy. The shift between ghrelin and other appetite-regulating hormones might translate into altered ability to regulate energy balance, affecting offspring's metabolic homeostasis.

Macrophage-derived human resistin promotes perivascular adipose tissue dysfunction in experimental inflammatory arthritis.

Cardiovascular disease (CVD) is the leading cause of death in rheumatoid arthritis (RA). Resistin is an adipokine that induces adipose tissue inflammation and activation of monocytes/macrophages via adenylate cyclase-associated protein-1 (CAP1). Resistin levels are increased in RA and might cause perivascular adipose tissue (PVAT) dysfunction, leading to vascular damage and CVD. This study aimed to investigate the role of resistin in promoting PVAT dysfunction by increasing local macrophage and inflammatory cytokines content in antigen-induced arthritis (AIA). Resistin pharmacological effects were assessed by using C57Bl/6J wild-type (WT) mice, humanized resistin mice expressing human resistin in monocytes-macrophages (hRTN+/-/-), and resistin knockout mice (RTN-/-) with AIA and respective controls. We investigated AIA disease activity and functional, cellular, and molecular parameters of the PVAT. Resistin did not contribute to AIA disease activity and its concentrations were augmented in the PVAT and plasma of WT AIA and hRTN+/-/- AIA animals. In vitro exposure of murine arteries to resistin impaired vascular function by decreasing the anti-contractile effect of PVAT. WT AIA mice and hRTN+/-/- AIA mice exhibited PVAT dysfunction and knockdown of resistin prevented it. Macrophage-derived cytokines, markers of types 1 and 2 macrophages, and CAP1 expression were increased in the PVAT of resistin humanized mice with AIA, but not in knockout mice for resistin. This study reveals that macrophage-derived resistin promotes PVAT inflammation and dysfunction regardless of AIA disease activity. Resistin might represent a translational target to reduce RA-driven vascular dysfunction and CVD.

Association of resistin (rs3138167) gene polymorphism with metabolic response after a hypocaloric Mediterranean diet / Asociación del polimorfismo del gen de la resistina (rs3138167) con la respuesta metabólica trasuna dieta mediterránea hipocalórica

Background: the single nucleotide polymorphism (SNP) (rs3138167) is a polymorphism that has been associated with metabolic disorder in obese subjects and its effect on the metabolic response after a dietary intervention has not been evaluated. Objective: our aim was to analyze the effects of the rs3138167 on metabolic changes secondary to weight loss with a hypocaloric diet with a Mediterranean pattern. Method: one thousand and eight Caucasian obese patients were evaluated. Before and after 12 weeks on a hypocaloric diet with Mediterranean pattern, an anthropometric evaluation and a biochemical analysis were performed. The statistical analysis was performed as a dominant model (CC vs CT + TT). Results: the values of insulin, HOMA-IR and resistin were higher in T allele carriers than non-T allele carriers in pre- and post-intervention time. In non-T allele carriers, resistin, insulin, HOMA-IR, triglycerides and C-reactive protein levels decreased. The improvement was statistically superior in non-T allele carriers; resistin (-1.2 ± 0.2 ng/dl; p = 0.02), triglycerides (-18.3 ± 4.3 mg/dl; p = 0.02), C-reactive protein (-2.6 ± 0.3 mg/dl; p = 0.02), insulin -4.4 ± 1.9 mUI/l; p = 0.02) and HOMA-IR (-2.1 ± 0.7; p = 0.03). Conclusion: we report an association of rs3138167 with a worse metabolic response (insulin, HOMA-IR, triglyceride and C-reactive protein) in T allele carriers after weight loss with a hypocaloric diet with Mediterranean pattern.(AU)

Antecedentes: el polimorfismo de nucleótido único (SNP) (rs3138167) se ha asociado con trastorno metabólico en sujetos obesos y no se ha evaluado su efecto sobre la respuesta metabólica después de una intervención dietética.Objetivo: nuestro objetivo fue analizar los efectos del polimorfismo rs3138167 sobre los cambios metabólicos secundarios a la pérdida de peso con una dieta hipocalórica de patrón mediterráneo. Métodos: se evaluaron 1.008 pacientes caucásicos con obesidad. Antes y tras 12 semanas de dieta hipocalórica con patrón mediterráneo, se realizaron una evaluación antropométrica y un análisis bioquímico. El análisis estadístico se realizó como un modelo dominante (CC vs. CT + TT). Resultados: los valores de insulina, HOMA-IR y resistina fueron más elevados en los portadores del alelo T, tanto antes como después de la intervención dietética. En los no portadores del alelo T, los niveles de resistina, insulina, HOMA-IR, triglicéridos y proteína C reactiva disminuyeron. Las mejorías fueron estadísticamente significativas, de manera superior en los no portadores del alelo T; resistina (-1,2 ± 0,2 ng/dl; p = 0,02), triglicéridos (-18,3 ± 4,3 mg/dl; p = 0,02), proteína C reactiva (-2,6 ± 0,3 mg/dl; p = 0,02), insulina -4,4 ± 1,9 mUI/l; p = 0,02) y HOMA-IR (-2,1 ± 0,7; p = 0,03). Conclusión: describimos una asociación del rs3138167 con una peor respuesta metabólica en los portadores del alelo T (insulina, HOMA-IR, triglicéridos y proteína C reactiva) tras la pérdida de peso con una dieta hipocalórica de patrón mediterráneo.(AU)

Circulatory resistin levels in inflammatory bowel disease: a systematic review and meta-analysis.

BACKGROUND: Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is a chronic relapsing-remitting systemic disease of the gastrointestinal tract with rising incidence. Studies have shown that adipocytes play a crucial role in patients with IBD by actively participating in systemic immune responses. The present study was designed to investigate the correlation between the circulatory levels of resistin, as an adipokine, and active and remission phases of IBD in comparison with healthy controls. METHODS: Relevant articles were retrieved from PubMed, Embase, the Web of Science, and Scopus from inception until June 2023. Estimation of the standardized mean difference (SMD) and 95% confidence interval (CI) for comparison of plasma/serum resistin levels between IBD patients, patients in remission, and healthy controls were conducted through random-effect meta-analysis. RESULTS: A total of 19 studies were included, assessing 1836 cases. Meta-analysis indicated that generally, serum/plasma resistin levels were higher in IBD patients in comparison with healthy controls (SMD 1.33, 95% CI 0.58 to 2.08, p-value < 0.01). This was true for each of the UC and CD separate analyses, as well. Moreover, it was shown that higher serum/plasma resistin levels were detected in the active phase of IBD than in the remission phase (SMD 1.04, 95% CI 0.65 to 1.42, p-value = 0.01). Finally, higher serum/plasma resistin levels were found in the remission phase compared to healthy controls (SMD 0.60, 95% CI 0.15 to 1.06, p-value < 0.01). CONCLUSION: The results of this systematic review and meta-analysis support the conclusion that circulating resistin levels are increased in IBD (both UC and CD). Also, higher resistin levels were recorded in the remission phase of IBD in comparison with healthy controls. This indicates that further studies may provide valuable insights into the role of resistin in the pathogenesis of IBD.

Label-Free Electrochemical Immunosensor Based on Conjugated Polymer Film Coated Disposable Electrode for Ultrasensitive Determination of Resistin Potential Obesity Biomarker.

A new label-free immunosensor was designed for sensitive detection of resistin obesity biomarker in human biological fluids. To construct a sensing interface, the monomer of double epoxy groups-substituted thiophene (TdiEpx) was synthesized for the fabrication of the biosensing system. A disposable indium tin oxide sheet was first modified by electrochemical polymerization of the TdiEpx monomer, and this robust and novel surface was characterized using different spectroscopic and electrochemical analyses. The double epoxy ends were linked to the amino ends of anti-resistin, and they served as binding points for the covalent binding of biomolecules. The double epoxy ends present in each TdiEpx monomer ensured an extensive surface area, which improved the quantity of attached anti-resistin. The determination of resistin antigen was based on the specific coupling of resistin with anti-resistin, and this interaction hindered the electron transfer reaction. The immunosensor introduced a wide linear range of 0.0125-15 pg/mL, a low detection limit of 4.17 fg/mL, and an excellent sensitivity of 1.38 kohm pg mL-1 cm2. In this study, a sandwich enzyme-linked immunosorbent assay spectrophotometric method was utilized as a reference technique for the quantitative analysis of resistin in human serum and saliva samples. Both measurements in clinical samples displayed correlations and high-correlation coefficients. In addition, this immunosensor had good storage stability, acceptable repeatability and reproducibility, high specificity, and good accuracy. The proposed immunosensor provided a simple and versatile impedimetric immunosensing platform and a promisingly sensitive way for clinical applications.

Interaction effect between low birthweight and resistin gene rs1862513 variant on insulin resistance and type 2 diabetes mellitus in adulthood: Toon Genome Study.

AIMS/INTRODUCTION: Gene-environment interactions are considered to critically influence type 2 diabetes mellitus development; however, the underlying mechanisms and specific interactions remain unclear. Given the increasing prevalence of low birthweight (LBW) influenced by the intrauterine environment, we sought to investigate genetic factors related to type 2 diabetes development in individuals with LBW. MATERIALS AND METHODS: The interaction between 20 reported type 2 diabetes susceptibility genes and the development of type 2 diabetes in LBW (<2,500 g) individuals in a population-based Japanese cohort (n = 1,021) was examined by logistic regression and stratified analyses. RESULTS: Logistic regression analyses showed that only the G/G genotype at the rs1862513 locus of the resistin gene (RETN), an established initiator of insulin resistance, was closely related to the prevalence of type 2 diabetes in individuals with LBW. Age, sex and current body mass index-adjusted stratified analyses showed a significant interaction effect of LBW and the RETN G/G genotype on fasting insulin, homeostatic model assessment 2-insulin resistance, Matsuda index and the prevalence of type 2 diabetes (all P-values for interaction <0.05). The adjusted odds ratio for type 2 diabetes in the LBW + G/G genotype group was 7.33 (95% confidence interval 2.43-22.11; P = 0.002) compared with the non-LBW + non-G/G genotype group. Similar results were obtained after excluding the influence of malnutrition due to World War II. CONCLUSIONS: Simultaneous assessment of LBW and the RETN G/G genotype can more accurately predict the risk of future type 2 diabetes than assessing each of these factors alone, and provide management strategies, including early lifestyle intervention in LBW population.

Role of Adipose Tissue Hormones in Pathogenesis of Cryptoglandular Anal Fistula.

The cryptoglandular perianal fistula is a common benign anorectal disorder that is managed mainly with surgery and in some cases may be an extremely challenging condition. Perianal fistulas are often characterized by significantly decreased patient quality of life. Lack of fully recognized pathogenesis of this disease makes it difficult to treat it properly. Recently, adipose tissue hormones have been proposed to play a role in the genesis of cryptoglandular anal fistulas. The expression of adipose tissue hormones and epithelial-to-mesenchymal transition (EMT) factors were characterized based on 30 samples from simple fistulas and 30 samples from complex cryptoglandular perianal fistulas harvested during surgery. Tissue levels of leptin, resistin, MMP2, and MMP9 were significantly elevated in patients who underwent operations due to complex cryptoglandular perianal fistulas compared to patients with simple fistulas. Adiponectin and E-cadherin were significantly lowered in samples from complex perianal fistulas in comparison to simple fistulas. A negative correlation between leptin and E-cadherin levels was observed. Resistin and MMP2 levels, as well as adiponectin and E-cadherin levels, were positively correlated. Complex perianal cryptoglandular fistulas have a reduced level of the anti-inflammatory adipokine adiponectin and have an increase in the levels of proinflammatory resistin and leptin. Abnormal secretion of these adipokines may affect the integrity of the EMT in the fistula tract. E-cadherin, MMP2, and MMP9 expression levels were shifted in patients with more advanced and complex perianal fistulas. Our results supporting the idea of using mesenchymal stem cells in the treatment of cryptoglandular perianal fistulas seem reasonable, but further studies are warranted.

Insulin resistance prior to term age in very low birthweight infants: a prospective study.

OBJECTIVE: To explore the glucose-related hormone profile of very low birthweight (VLBW) infants and assess the association between neonatal hyperglycaemia and insulin resistance during the admission period. DESIGN: A prospective observational study-the Very Low Birth Weight Infants, Glucose and Hormonal Profiles over Time study. SETTING: A tertiary neonatal intensive care unit and four neonatal units in county hospitals in Sweden. PATIENTS: 48 infants born <1500 g (VLBW) during 2016-2019. OUTCOME MEASURES: Plasma concentrations of glucose-related hormones and proteins (C-peptide, insulin, ghrelin, glucagon-like peptide 1 (GLP-1), glucagon, leptin, resistin and proinsulin), insulin:C-peptide and proinsulin:insulin ratios, Homoeostatic Model Assessment 2 (HOMA2) and Quantitative Insulin Sensitivity Check (QUICKI) indices, measured on day of life (DOL) 7 and at postmenstrual age 36 weeks. RESULTS: Lower gestational age was significantly associated with higher glucose, C-peptide, insulin, proinsulin, leptin, ghrelin, resistin and GLP-1 concentrations, increased HOMA2 index, and decreased QUICKI index and proinsulin:insulin ratio. Hyperglycaemic infants had significantly higher glucose, C-peptide, insulin, leptin and proinsulin concentrations, and lower QUICKI index, than normoglycaemic infants. Higher glucose and proinsulin concentrations and insulin:C-peptide ratio, and lower QUICKI index on DOL 7 were significantly associated with longer duration of hyperglycaemia during the admission period. CONCLUSIONS: VLBW infants seem to have a hormone profile consistent with insulin resistance. Lower gestational age and hyperglycaemia are associated with higher concentrations of insulin resistance markers.

The strong inverse association between plasma concentrations of soluble tumor necrosis factor receptors type 1 with adiponectin/leptin ratio in older women.

Complex inflammatory crosstalk between muscular and adipose organs during ageing is controlled by adipokines and myokines. The Adiponectin/Leptin ratio (A/L ratio) has proven to be a promising biomarker for identifying insulin sensitivity, cardiovascular risk and adipose tissue inflammation. Although the A/L ratio has been related to inflammatory conditions, its ability to associate with or indicate the behavior of other inflammatory mediators remains unknown. The present study aimed to verify the association between the A/L ratio and a panel of inflammatory biomarkers in community-dwelling older women. The plasmatic concentrations of adiponectin, leptin, resistin, brain-derived neurotrophic factor (BDNF), interferon-gamma (IFN-γ), interleukins 2, 4, 5, 6, 8 and 10, tumour necrosis factor (TNF) and its soluble receptors (sTNF-r) 1 and 2 were evaluated in 71 community-dwelling older women with 75 (±7) years. The A/L ratio was negative and inverse correlated with BNDF (r = -0.29; p = 0.01), IL-8 (r = -0.37; p = 0.001) and sTNFr- 1 (r = -0.98; p < 0.001) levels. A strong and inverse association, with proportional effect, between A/L ratio and sTNFr-1 concentrations was found (Adjusted R2 = 0.22; ß = -0.48; p > 0.001). It suggests that the presence of sTNFr-1 causes an inflammatory effect that affect cross-talk between muscle and adipose tissue, contributing to pro-inflammatory imbalance, which may have molecular and functional consequences. In addition, we provide insights into diagnostic biomarkers for inflammation, especially related to muscle wasting and intrinsic capacity in older people.

Serum resistin and lipid profile in primigravida females with and without preeclampsia: An analytical cross-sectional study.

OBJECTIVE: To measure and compare the serum levels of resistin and lipid profile parameters in primigravida females with and without preeclampsia. Methods: The analytical cross-sectional study was conducted at the Department of Physiology and Cell Biology, University of Health Sciences, Lahore, Pakistan, from 2018 to 2020, and comprised primigravida females having gestational age 30-36 weeks. Those with preeclampsia constituted group 1, while normotensive females constituted group 2. All the participants were subjected to detailed history and general physical examination. Serum resistin levels were measured by enzymelinked immunosorbent assay, and lipid profile parameters were measured using the colorimetric method. Data was analysed using SPSS 20. RESULTS: Of the 80 women, 40(50%) were in group 1 with mean age 23.07±2.10 years and mean gestation age 33.45±2.30 weeks. There were 40(50%) women in group 2 with mean age 23.02±2.11 years and mean gestational age 34.45±1.75 weeks. Mean serum resistin was significantly higher in group 1 compared to group 2 (p<0.02). Mean levels of lipid parameters were significantly different between the groups (p˂0.05). Conclusion: Preeclampsia was found to be associated with higher levels of resistin and lipid parameters compared to normal pregnancy.

Predictive value of adipokines for the severity of acute pancreatitis: a meta-analysis.

BACKGROUND: Severe acute pancreatitis (SAP) is a dangerous condition with a high mortality rate. Many studies have found an association between adipokines and the development of SAP, but the results are controversial. Therefore, we performed a meta-analysis of the association of inflammatory adipokines with SAP. METHODS: We screened PubMed, EMBASE, Web of Science and Cochrane Library for articles on adipokines and SAP published before July 20, 2023. The quality of the literature was assessed using QUADAS criteria. Standardized mean differences (SMD) with 95% confidence intervals (CI) were calculated to assess the combined effect. Subgroup analysis, sensitivity analysis and publication bias tests were also performed on the information obtained. RESULT: Fifteen eligible studies included 1332 patients with acute pancreatitis (AP). Pooled analysis showed that patients with SAP had significantly higher serum levels of resistin (SMD = 0.78, 95% CI:0.37 to 1.19, z = 3.75, P = 0.000). The difference in leptin and adiponectin levels between SAP and mild acute pancreatitis (MAP) patients were not significant (SMD = 0.30, 95% CI: -0.08 to 0.68, z = 1.53, P = 0.127 and SMD = 0.11, 95% CI: -0.17 to 0.40, z = 0.80, P = 0.425, respectively). In patients with SAP, visfatin levels were not significantly different from that in patients with MAP (SMD = 1.20, 95% CI: -0.48 to 2.88, z = 1.40, P = 0.162). CONCLUSION: Elevated levels of resistin are associated with the development of SAP. Resistin may serve as biomarker for SAP and has promise as therapeutic target.

A new immunosensing platform based on conjugated Poly(ThidEp-co-EDOT) copolymer for resistin detection, a new obesity biomarker.

The design of a novel electrochemical impedimetric biosensor for label-free analysis of resistin, a biomarker for obesity, is reported. For the fabrication of the immunosensor, a novel approach composed of electrochemical copolymerization of double epoxy groups-substituted thiophene (ThidEp) and 3,4-Ethylenedioxythiophene (EDOT) monomers was utilized. Anti-resistin antibodies were covalently attached to the copolymer-coated electrode. The capture of resistin antigens by anti-resistin antibodies caused significant variations in charge transfer resistance (Rct) because of the immunoreactions between these proteins. Under optimum experimental variables, the changes in impedance signals were employed for the determination of resistin antigen concentration, and the prepared immunosensor based on conjugated copolymer illustrated a wide linear range between 0.0125 and 22.5 pg/mL, a low detection limit (LOD) of 3.71 fg/mL, and a good sensitivity of 1.22 kΩ pg-1mL cm2. The excellent analytical performance of the resistin immunosensor in terms of selectivity, sensitivity, repeatability, reproducibility, storage stability, and low detection limit might be attributed to the conductive copolymer film layer generation on the disposable indium tin oxide (ITO) platform. The capability of this system for the determination of resistin in human serum and saliva samples was also tested. The immunosensor results were in accordance with the enzyme-linked immunosorbent assay (ELISA) results. The matrix effects of human serum and saliva were also investigated, and the proposed immunosensor displayed good recovery ranging from 95.91 to 106.25%. The engineered immunosensor could open new avenues for obesity monitoring.

Pre-diagnostic circulating resistin concentrations and mortality among individuals with colorectal cancer: Results from the European Prospective Investigation into Cancer and Nutrition study.

Resistin is a protein involved in inflammation and angiogenesis processes and may play a role in the progression of colorectal cancer (CRC). However, it remains unclear whether resistin is associated with increased mortality after CRC diagnosis. We examined pre-diagnostic serum resistin concentrations in relation to CRC-specific and all-cause mortality among 1343 incident CRC cases from the European Prospective Investigation into Cancer and Nutrition cohort. For CRC-specific mortality as the primary outcome, hazard ratios (HRs) and 95% confidence intervals (95% CI) were estimated from competing risk analyses based on cause-specific Cox proportional hazards models and further in sensitivity analyses using Fine-Gray proportional subdistribution hazards models. For all-cause mortality as the secondary outcome, Cox proportional hazards models were used. Subgroup analyses were performed by sex, tumor subsite, tumor stage, body mass index and time to CRC diagnosis. Resistin was measured on a median of 4.8 years before CRC diagnosis. During a median follow-up of 8.2 years, 474 deaths from CRC and 147 deaths from other causes were observed. Resistin concentrations were not associated with CRC-specific mortality (HRQ4vsQ1 = 0.95, 95% CI: 0.73-1.23; Ptrend = .97; and HRper doubling of resistin concentration = 1.00; 95% CI: 0.84-1.19; P = .98) or all-cause mortality. Results from competing risk (sensitivity) analysis were similar. No associations were found in any subgroup analyses. These findings suggest no association between pre-diagnostic circulating resistin concentrations and CRC-specific or all-cause mortality among persons with CRC, and the potential insignificance of resistin in CRC progression.

The effect of resistin on the redox state of breast cancer cells.

PURPOSE: Resistin is an inflammatory cytokine secreted mostly by adipocytes and immune cells that plays a role in the development of insulin resistance, diabetes, and cancer. We hypothesized that resistin's inflammatory activity influences the free radical and oxidative stress pathways. METHODS: We used human breast carcinogenic (MCF-7 and MDA-MB-231) and non-carcinogenic (MCF-10A) cells in this investigation and correlated the absorbed resistin concentration with the change in oxidative stress (TBARS, carbonated proteins) and antioxidant activity (Antioxidant Capacity, SuperOxideDismutase, CATalase, Glutathione Peroxidase). RESULTS: Resistin was substantially more effective as a prooxidant at lower (12.5 ng/ml) concentrations, than at higher concentrations (25.0 ng/ml). Vitamin C did not appear to be an effective oxidative stress protector at antioxidant concentrations of 5.10-4 M. Leptin, at 100 ng/ml, did not result in conclusive oxidative stress or antioxidant defence stimulation, as expected. CONCLUSION: Taken together, the findings support resistin's role as a non-oxidative stress marker and a metabolic signaling molecule.

Adipokines and stroke: A systematic review and meta-analysis of disease risk and patient outcomes.

Obesity is reported to increase stroke risk, with adipocyte-derived cytokines or adipokines implicated as mediators. However, the relationship between adipokines and stroke is not well clarified. Thus, we aimed to evaluate the association of adipokines with stroke using fully adjusted risk estimates that incorporated body mass index in a meta-analysis. Data from 52 studies (62,428 patients) were pooled in a random-effects meta-analysis. Adiponectin was independently associated with a lower risk of pre-existing stroke (adjusted odds ratio: 0.64 [95% confidence interval: 0.46-0.88], p < 0.01), whereas leptin (1.08 [1.00-1.17], p = 0.04), resistin (1.06 [1.04-1.08], p < 0.01) and visfatin (1.04 [1.01-1.07], p = 0.01) are associated with a higher risk of stroke, but none with incident stroke. Adipokines independently associated with an ischaemic stroke subtype were adiponectin (0.48 [0.30-0.77], p < 0.01), leptin (1.10 [1.01-1.20], p = 0.04), and resistin (1.06 [1.04-1.08], p < 0.01). Fatty acid-binding protein-4 (FABP-4) independently predicted 6-month poor functional outcomes in stroke patients (adjusted hazard ratio: 1.09 [1.06-1.12], p < 0.01); whereas both FABP-4 (1.17 [1.03-1.34], p = 0.01) and visfatin (1.24 [1.00-1.55], p = 0.05) were predictive of 6-month mortality. Adipokines are associated with a greater risk of pre-existing stroke, but not with the relationship with incident stroke. Adipokines, such as FABP-4 and visfatin, may serve as biomarkers of stroke severity and worsening of stroke outcomes.

Resistin in endocrine pancreas of sheep: Presence and expression related to different diets.

Resistin (RETN), a recently discovered adipokine, is a cysteine-rich and secretory protein produced by adipocytes. RETN has been detected in several tissues, including human and laboratory animals' pancreas, wherein impairs glucose tolerance and insulin (INS) action and causes INS resistance. This study aims to evaluate the presence and expression of RETN in the pancreas of 15 adult female sheep reared on Apennine pastures, which show a decrease in their nutritional value due to the drought stress linked to the increasing summer aridity. The sheep were divided into 3 groups according to the diet they were subjected to: maximum pasture flowering (MxF) group, maximum pasture dryness (MxD) group, and experimental (Exp) group which received a feed supplementation in addition to the MxD group feeding. Immunohistochemistry and immunofluorescence were performed on formalin-fixed and paraffin-embedded sections of the pancreas to detect the RETN presence and to evaluate the co-localization of RETN with both glucagon (GCG)- and INS-producing cells. In addition, the expression of the three molecules was evaluated also in relation to different diets. RETN was observed only in the endocrine pancreas, showing a wide distribution throughout the pancreatic islets with few negative cells and the RETN producing cells colocalized with both α cells and ß cells. No differences in distribution and immunostaining intensity of RETN, GCG and INS were observed among the three groups. Quantitative PCR showed the expression of RETN, GCG and INS in all tested samples. No significant differences were observed for RETN and GCG among all three groups of sheep. Instead, a high statistically significant expression of INS was detected in the MxF group with respect to the Exp and MxD groups. These results highlight the localization of RETN in GCG- and INS-secreting cells involved in glucose homeostasis suggesting a modulatory role for RETN. Furthermore, the RETN expression is not influenced by food supplementation and thus is not affected by diet.

Adipocytokines levels as potential biomarkers for discriminating patients with a diagnosis of depressive disorder from healthy controls.

BACKGROUND: Depressive disorder is a complex mental health condition in which the etiopathogenesis involves several factors. Suitable biomarkers for the development of depression have not yet been established. Alterations in cytokines are assumed to be involved in the pathophysiology of depressive disorder. Adipokines (also known as adipocytokines) are important factors that not only regulate the energy balance but also regulate the inflammatory and immune responses. This study investigated the serum levels of adiponectin, leptin, resistin, chemerin, and fetuin A and the possible role of these adipokines in depressive disorder. METHODS: We recruited a total of 73 patients diagnosed with recurrent depressive disorder (rDD) and 54 age- and sex-matched healthy controls (HCs). Serum adipocytokines were determined using ELISA kits (R&D, USA). The serum levels of the investigated molecules between depressive patients and HCs were compared, and diagnostic values were evaluated using the receiver operating characteristic (ROC) curve method for discriminating depressive patients from HCs. Correlations between the molecules and clinical variables were also evaluated. RESULTS: Patients with rDD had lower levels of serum adiponectin and chemerin and higher levels of serum leptin, resistin and fetuin A (p < 0.05) vs. controls. Moreover, ROC curve analysis showed that the area under the curve (AUC) values of above set of adipocytkines were >0.7, with a sensitivity and specificity over 80% in discriminating patients with rDD from HCs. CONCLUSIONS: These results suggest that circulating adipocytokies may hold promise as biomarkers for the diagnosis of rDD.