Resistin predicts disease severity and survival in patients with pulmonary arterial hypertension.

BACKGROUND: Abnormal remodeling of distal pulmonary arteries in patients with pulmonary arterial hypertension (PAH) leads to progressively increased pulmonary vascular resistance, followed by right ventricular hypertrophy and failure. Despite considerable advancements in PAH treatment prognosis remains poor. We aim to evaluate the potential for using the cytokine resistin as a genetic and biological marker for disease severity and survival in a large cohort of patients with PAH. METHODS: Biospecimens, clinical, and genetic data for 1121 adults with PAH, including 808 with idiopathic PAH (IPAH) and 313 with scleroderma-associated PAH (SSc-PAH), were obtained from a national repository. Serum resistin levels were measured by ELISA, and associations between resistin levels, clinical variables, and single nucleotide polymorphism genotypes were examined with multivariable regression models. Machine-learning (ML) algorithms were applied to develop and compare risk models for mortality prediction. RESULTS: Resistin levels were significantly higher in all PAH samples and PAH subtype (IPAH and SSc-PAH) samples than in controls (P < .0001) and had significant discriminative abilities (AUCs of 0.84, 0.82, and 0.91, respectively; P < .001). High resistin levels (above 4.54 ng/mL) in PAH patients were associated with older age (P = .001), shorter 6-min walk distance (P = .001), and reduced cardiac performance (cardiac index, P = .016). Interestingly, mutant carriers of either rs3219175 or rs3745367 had higher resistin levels (adjusted P = .0001). High resistin levels in PAH patients were also associated with increased risk of death (hazard ratio: 2.6; 95% CI: 1.27-5.33; P < .0087). Comparisons of ML-derived survival models confirmed satisfactory prognostic value of the random forest model (AUC = 0.70, 95% CI: 0.62-0.79) for PAH. CONCLUSIONS: This work establishes the importance of resistin in the pathobiology of human PAH. In line with its function in rodent models, serum resistin represents a novel biomarker for PAH prognostication and may indicate a new therapeutic avenue. ML-derived survival models highlighted the importance of including resistin levels to improve performance. Future studies are needed to develop multi-marker assays that improve noninvasive risk stratification.

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.

The Association Between the Severity of Psoriasis and Obesity Based on the Analysis of Visceral Fat Index and Serum Levels of Tumor Necrosis Factor-α, Interleukin-6, and Resistin.

Aim of this study was to investigate the relationship between the severity of psoriasis and obesity based on the analysis of the visceral fat index and serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and resistin. The study included 50 patients with psoriasis and 30 subjects in the control group. The measured parameters were height, weight, waist circumference, visceral fat index, and serum levels of TNF-α, IL-6, and resistin. The severity of the disease was evaluated using the psoriasis area and severity index (PASI). Visceral fat index was measured using the method of bioelectrical impedance analysis. Serum levels of TNF-α, IL-6, and resistin were correlated with visceral fat index, and the relationship of all these parameters with psoriasis severity was also analyzed. Patients with psoriasis have a significantly higher body mass index, waist circumference, and visceral fat index compared with the control group. Elevated serum levels of TNF-α, IL-6, and resistin, as well as a correlation with psoriasis severity and visceral fat index was also found in the patient group. Visceral fat index was a better indicator of the relationship between psoriasis severity and obesity than waist circumference and body mass index. We concluded that serum levels of TNF-α, IL-6, and resistin could be useful in assessing psoriasis activity and optimizing therapeutic strategies. It is suggested that visceral fat index should be evaluated in all patients with psoriasis, especially before the decision on systemic therapy.

Serum Resistin Levels and Related Genetic Variants Are Associated With Bone Mineral Density in Postmenopausal Women.

Background: Osteoporosis is a multifactorial disorder and a number of genetic variants or loci responsible for bone mineral density (BMD) have been identified. Resistin, a novel adipokine has diverse role in human body including its function in bone remodeling. The objective of this study was to see the association of serum resistin levels and related genetic variants (rs3931020, rs13144478) with BMD in postmenopausal females. Methods: This comparative analytical study was conducted on postmenopausal osteoporotic (n=101), osteopenic (n=77) and non-osteoporotic (n=74) females. For comparison and correlational analysis, Kruskal-Wallis test and Spearman's rho correlation were used respectively. Hardy-Weinberg equilibrium (HWE) was calculated by using Chi-square test (χ2). Results: There was significant difference in the serum levels of resistin (p <0.001), among the three groups. Significant negative correlation of resistin was observed with BMD at various sites. Serum resistin levels were significantly low in the rs3931020 AA homozygous genotype (p = 0.010), and significantly high in the rs13144478 AT heterozygous genotype (p = 0.020), BMD at all sites except left femoral neck was significantly high in rs3931020 AA genotype, while BMD at lumbar spine, left hip and total BMD were significantly low in the rs13144478 TT homozygotes. Conclusion: High serum resistin levels are associated with low BMD and single nucleotide variation in rs3931020 and rs13144478 may lead to high serum resistin levels and low bone mineral density. Resistin can serve as a new genetic marker, potential therapeutic target and predictor of osteoporosis.

Increased serum resistin but not G-CSF levels are associated in the pathophysiology of major depressive disorder: Findings from a case-control study.

BACKGROUND: Many studies have predicted major depressive disorder (MDD) as the leading cause of global health by 2030 due to its high prevalence, disability, and illness. However, the actual pathophysiological mechanism behind depression is unknown. Scientists consider alterations in cytokines might be tools for understanding the pathogenesis and treatment of MDD. Several past studies on several inflammatory cytokine expressions in MDD reveal that an inflammatory process is activated, although the precise causes of that changes in cytokine levels are unclear. Therefore, we aimed to investigate resistin and G-CSF in MDD patients and controls to explore their role in the pathogenesis and development of depression. METHODS: We included 220 participants in this study. Among them, 108 MDD patients and 112 age-sex matched healthy control (HCs). We used DSM-5 to evaluate study participants. Also, we applied the Ham-D rating scale to assess the severity of patients. Serum resistin and G-CSF levels were measured using ELISA kits (BosterBio, USA). RESULTS: The present study observed increased serum resistin levels in MDD patients compared to HCs (13.82 ± 1.24ng/mL and 6.35 ± 0.51ng/mL, p <0.001). However, we did not find such changes for serum G-CSF levels between the groups. Ham-D scores showed a significant correlation with serum resistin levels but not G-CSF levels in the patient group. Furthermore, ROC analysis showed a fairly predictive performance of serum resistin levels in major depression (AUC = 0.746). CONCLUSION: The present study findings suggest higher serum resistin levels are associated with the pathophysiology of MDD. This elevated serum resistin level may serve as an early risk assessment indicator for MDD. However, the role of serum G-CSF in the development of MDD is still unclear despite its neuroprotective and anti-inflammatory effects.

Roles of plasma leptin and resistin in novel subgroups of type 2 diabetes driven by cluster analysis.

BACKGROUND: A novel classification has been introduced to promote precision medicine in diabetes. The current study aimed to investigate the relationship between leptin and resistin levels with novel refined subgroups in patients with type 2 diabetes mellitus (T2DM). METHODS: The k-means analysis was conducted to cluster 541 T2DM patients into the following four subgroups: mild obesity-related diabetes (MOD), severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD) and mild age-related diabetes (MARD). Individuals meeting the exclusion criteria were eliminated, the data for 285 patients were analyzed. Characteristics were determined using various clinical parameters. Both the leptin and resistin levels were determined using enzyme-linked immunosorbent assay. RESULTS: The highest levels of plasma leptin were in the MOD group with relatively lower levels in the SIDD and SIRD groups (P < 0.001). The SIRD group had a higher resistin concentration than the MARD group (P = 0.024) while no statistical significance in resistin levels was found between the SIDD and MOD groups. Logistic regression demonstrated that plasma resistin was associated with a higher risk of diabetic nephropathy (odds ratios (OR) = 2.255, P = 0.001). According to receiver operating characteristic (ROC) curves, the area under the curve (AUC) of resistin (0.748, 95% CI 0.610-0.887) was significantly greater than that of HOMA2-IR (0.447, 95% CI 0.280-0.614) (P < 0.05) for diabetic nephropathy in the SIRD group. CONCLUSIONS: Leptin levels were different in four subgroups of T2DM and were highest in the MOD group. Resistin was elevated in the SIRD group and was closely related to diabetic nephropathy.

Expression of immune-related proteins and their association with neuropeptides in adolescent patients with anorexia nervosa.

Anorexia nervosa (AN) is a metabo-psychiatric disorder where alterations of cytokines, neuropeptides, neurotransmitters, and the interactions between these factors can play an important role. Thus, the primary goal of the presented study was a cross-sectional analysis of immune-related proteins in patients with AN. Moreover, the correlations between these molecules and selected neuropeptides were studied. Twenty-five adolescent inpatients girls in the acute stage of a restrictive type of AN were enrolled in the study within the first year of the disease. Additionally, thirty similar in age and height controls (CG) were also assessed. The levels of 24 immune-related proteins, including cytokines, chemokines, and proteases, were measured. Moreover, selected adipocytokines, gastrointestinal hormones, and centrally produced neuropeptides levels were determined. Finally, the correlations between these molecules were analyzed. The fasting levels of CXCL1, CXCL9, FGF2, GrB, IL1, IL6, IL8, MMP8, MMP9, CTSS were statistically lower in AN than in the CG. The concentrations of many immune-related proteins remain unchanged despite their metabolic and mental condition. Moreover, significant correlations were found between leptin and CXCL1, CXCL9, GrB, IL1, IL6, and MMP8. Leptin receptors were correlated with GrB, while resistin was associated with MMP9. Our findings suggest that the initial stage of restrictive AN among adolescents within the first year of the disease is not connected with a pro-inflammatory state. Some immune-related protein changes may be associated with altered neuropeptides, primarily leptin, its receptors, and resistin. Future research should clarify which changes are primary and secondary to weight loss and whether these changes normalize with increasing weight. This would aid in understanding the complex etiopathogenesis of AN and in the search for new methods of treatment.

Serum resistin is predictive marker of development of new digital ulcers in systemic sclerosis.

Systemic sclerosis (SSc) is autoimmune disease characterized by endothelial dysfunction and microvascular damage. Resistin has been implied in microvascular dysfunction. Objective of this study is to evaluate the association between baseline resistin and development of new digital ulcers (DUs) in SSc patients. At baseline, serum resistin has been assessed in 70 female SSc patients and 26 healthy controls (HC). In SSc patients, clinical assessment was performed at baseline and after a 52-weeks follow-up. Serum resistin level was increased in SSc patients compared to HC [5.89 ng/ml (2.5 ng/ml-8.1 ng/ml) vs 2.3 ng/ml (0.4 ng/ml-2.4 ng/ml), p = 0.0004)]. Resistin was lower (p = 0.005) in SSc patients with early capillaroscopic pattern than patients with active or late capillaroscopic pattern [2.49 ng/ml (0.89 ng/ml-5.81 ng/ml) vs 7.11 ng/ml (3.48 ng/ml-11.35 ng/ml) and 6.49 ng/ml (3.35 ng/ml-8.87 ng/ml), respectively]. After a 52-weeks follow-up, 34 (48.6%) patients developed new DUs. Median serum resistin was significantly higher in patients with new DUs than in patients without new DUs [6.54 ng/ml (3.35 ng/ml-11.02 ng/ml) vs 4.78 ng/ml (1.06 ng/ml-7.6 ng/ml), p = 0.019]. Kaplan-Meier curves show a significantly reduced free survival from DUs in patients with increased resistin (p = 0.002). In multivariate analysis, resistin is associated with the development of new DUs. Increased serum resistin level is a predictive marker of new DUs in SSc.

Positive Correlation of Serum Resistin Level with Peripheral Artery Disease in Patients with Chronic Kidney Disease Stage 3 to 5.

Chronic kidney disease (CKD) is associated with higher risk of cardiovascular disease-related ischemic events, which includes peripheral arterial disease (PAD). PAD is a strong predictor of future cardiovascular events, which can cause significant morbidity and mortality. Resistin has been found to be involved in pathological processes leading to CVD. Therefore, we aim to investigate whether resistin level is correlated with PAD in patients with non-dialysis CKD stage 3 to 5. There were 240 CKD patients enrolled in this study. Ankle-brachial index (ABI) values were measured using the automated oscillometric method. An ABI value < 0.9 defined the low ABI group. Serum levels of human resistin were determined using a commercially available enzyme immunoassay. Thirty CKD patients (12.5%) were included in the low ABI group. Patients in the low ABI group were older and had higher resistin levels as well as higher diabetes mellitus, hypertension and habit of smoking, and lower estimated glomerular filtration rate than patients in the normal ABI group. After the adjustment for factors that were significantly associated with PAD by multivariate logistic regression analysis, age and serum resistin level were independent predictors of PAD. A high serum resistin level is an independent predictor of PAD in non-dialysis CKD stage 3 to 5.

Association of circulating leptin, adiponectin, and resistin concentrations with long-term breast cancer prognosis in a German patient cohort.

Adipokines including leptin, adiponectin and resistin have been linked to risk of obesity-related cancers potentially through low-grade chronic inflammation pathways. We aimed to assess the role of post-diagnosis circulating adipokines on long-term prognosis in a prospective breast cancer cohort. Adipokines were measured in blood collected at baseline shortly after diagnosis (2002-2005) and at follow-up (2009) from 3112 breast cancer patients enrolled in the population-based MARIE study. Half of the patients had measurements at both time-points. All-cause mortality, breast cancer specific mortality and recurrences were ascertained up to June 2015 (11 years median follow-up). Associations with time-varying adipokine concentrations overall and stratified by estrogen and progesterone receptor (ERPR) were evaluated using adjusted proportional hazard regression. At baseline (n = 2700) and follow-up (n = 2027), median concentrations for leptin, adiponectin and resistin were 4.6 and 2.7 ng/ml, 24.4 and 30.0 mg/l, 15.4 and 26.2 ng/ml, respectively. After adjustment, there was no evidence for associations between adipokines and any outcome overall. In ERPR negative tumors, highest vs. lowest quintile of adiponectin was significantly associated with increased breast cancer specific mortality (HR 2.51, 95%CI 1.07-5.92). Overall, post-diagnosis adipokines were not associated with long-term outcomes after breast cancer. In patients with ERPR negative tumors, higher concentrations of adiponectin may be associated with increased breast cancer specific mortality and warrant further investigation.

Associations of Serum Resistin With the Severity and Prognosis in Patients With Community-Acquired Pneumonia.

Background: Resistin is an endogenous ligand of Toll-like receptor 4 that activates several inflammatory signals. But the physiological function of resistin in community-acquired pneumonia (CAP) remains unknown. The goal of this research was to explore the associations between serum resistin and the severity and prognosis in CAP patients through a retrospective cohort study. Methods: All 212 CAP patients and 106 healthy cases were enrolled. Demographic characteristics were extracted. Serum resistin was determined via enzyme-linked immunosorbent assay. The prognosis was tracked in CAP patients. Results: Serum resistin on admission was raised in CAP patients compared with control cases. The level of resistin was gradually increased in parallel with CAP severity scores in CAP patients. Pearson and Spearman analyses revealed that serum resistin was positively correlated with CAP severity scores, white blood cells, urea nitrogen, creatinine, and inflammatory cytokines among CAP patients. There were negative relationships between resistin and hematocrit and albumin in CAP patients. Besides, linear and logistic regression analyses further indicated that serum resistin on admission was positively associated with CAP severity scores among CAP patients. Follow-up research revealed that serum resistin elevation on admission prolonged hospital stay in CAP patients. Conclusion: Serum resistin on admission is positively correlated with the severity and hospital stay in CAP patients, indicating that resistin may be involved in the physiological process of CAP. Serum resistin may be a potential biomarker in the diagnosis and prognosis for CAP.

Positive effect of combined exercise on adipokines levels and pubertal signs in overweight and obese girls with central precocious puberty.

BACKGROUND: The prevalence of precocious puberty is increasing. Obesity has been demonstrated to be associated with changes in the adipokine profile and incidence of early puberty in girls. This study assessed the pubertal signs, the levels of adiponectin, resistin, and tumor necrosis factor-alpha (TNF-α) after 12 weeks of combined exercise and 4 weeks of detraining in overweight and obese girls with precocious puberty. METHODS: Thirty overweight and obese girls (aged 7-9) with precocious puberty, who had received Triptorelin, were randomly divided into two groups (15 exercise and 15 control). Initially, serum levels of adiponectin, resistin, TNF-α, luteinising hormone (LH), and follicle-stimulating hormone (FSH) and the signs of puberty progression (bone age, uterine length, and ovarian volume) were measured. The exercise group performed 60 min of combined (aerobic and resistance) exercise three times/week for 12 weeks. The control group did not receive any exercise. 48 h after the last training session and after 4 weeks of detraining, all research variables were measured (also in the control group). The statistical method used for data analysis was repeated measures ANOVA. RESULTS: In the exercise group, adiponectin significantly increased and resistin significantly decreased after 12 weeks. After 4 weeks of detraining, adiponectin significantly decreased, but resistin significantly increased. TNF-α levels did not change significantly during the study. There was no significant difference in all of the factors in the control group. Throughout the 16-week study period, the rate of puberty and LH significantly decreased in both exercise and control groups, but FSH, LH/FSH and ovarian volume significantly decreased in the exercise group alone (P<0.05). CONCLUSIONS: Combined exercise increased adiponectin and decreased resistin and the rate of puberty. However, after 4 weeks of detraining, these effects diminished but did not disappear. TRIAL REGISTRATION: IRCT, IRCT56471. Registered 25 may 2021 - Retrospectively registered, https://fa.irct.ir/user/profile.

Maternal Plasma and Amniotic Fluid LBP, Pentraxin 3, Resistin, and IGFBP-3: Biomarkers of Microbial Invasion of Amniotic Cavity and/or Intra-amniotic Inflammation in Women with Preterm Premature Rupture of Membranes.

BACKGROUND: We sought to determine whether lipopolysaccharide binding protein (LBP), pentraxin 3, resistin, and insulin-like growth factor binding protein (IGFBP)-3 in plasma and amniotic fluid (AF) can predict microbial invasion of the amniotic cavity (MIAC), intra-amniotic inflammation (IAI), and microbial-associated IAI in women with preterm premature rupture of membranes (PPROM). METHODS: This was a retrospective cohort study involving 168 singleton pregnant women with PPROM. AF obtained via amniocentesis was cultured and assayed for interleukin (IL)-6 to define IAI and for IL-8 to compare with AF biomarkers. Plasma samples were collected at the time of amniocentesis, and C-reactive protein (CRP) levels in serum were compared with plasma biomarkers. The stored plasma and AF samples were assayed for LBP, pentraxin 3 (PTX3), resistin, and IGFBP-3 by ELISA. RESULTS: Multivariate logistic regression analysis revealed that: 1) elevated plasma and AF levels of LBP were independently associated with increased risks of MIAC, IAI, and microbial-associated IAI; 2) elevated AF, but not plasma, PTX3, and resistin levels were independently associated with increased risks of MIAC, IAI, and microbial-associated IAI; 3) decreased IGFBP-3 levels in the plasma were independently associated with only IAI, whereas those in the AF were associated with only microbial-associated IAI. Among the tested biomarkers, AF PTX3 and resistin had the highest predictive performance for MIAC, IAI, and microbial-associated IAI (area under the curves [AUC] = 0.85-0.95), which is similar to the performance of AF IL-8. The AUCs of the plasma LBP and IGFBP-3 were similar to that of serum CRP with respect to IAI. CONCLUSION: Maternal plasma LBP and IGFBP-3 are potential biomarkers for the non-invasive identification of IAI in women with PPROM, with a similar accuracy to the serum CRP level. AF LBP, PTX3, resistin, and IGFBP-3 may be involved in the intra-amniotic inflammatory responses in PPROM complicated by MIAC.

Association of ANGPTL8 and Resistin With Diabetic Nephropathy in Type 2 Diabetes Mellitus.

Background: Previous studies showed altered angiopoietin-like protein-8 (ANGPTL-8) and resistin circulating levels in type 2 diabetes mellitus (T2DM). Whether or not the alteration in ANGPTL-8 and resistin level can be a predictive maker for increased diabetic nephropathy risk remains unclear. Aim: To Investigate the possible association of ANGPTL-8 and resistin with DN, and whether this association is affected by NAFLD status. Methods: A total of 278 T2DM patients were enrolled. Serum levels of ANGPTL8, resistin, BMI, blood pressure, duration of diabetes, glycosylated hemoglobin (HbA1c), fasting blood glucose (FPG), hypersensitive C-reactive protein (hs-CRP), lipid profile, liver, and kidney function tests were assessed. The relationship between DN with ANGPTL8 and resistin was analyzed in the unadjusted and multiple-adjusted regression models. Results: Serum levels of ANGPTL8 and resistin were significantly higher in DN compared with T2DM subjects without DN (respectively; P <0.001), especially in non-NAFLD populations. ANGPTL8 and resistin showed positive correlation with hs-CRP (respectively; P<0.01), and negative correlation with estimated GFR (eGFR) (respectively; P=<0.001) but no significant correlation to HOMA-IR(respectively; P>0.05). Analysis showed ANGPTL8 levels were positively associated with resistin but only in T2DM patients with DN(r=0.1867; P<0.05), and this significant correlation disappeared in T2DM patients without DN. After adjusting for confounding factors, both ANGPTL8(OR=2.095, 95%CI 1.253-3.502 P=0.005) and resistin (OR=2.499, 95%CI 1.484-4.208 P=0.001) were risk factors for DN. Data in non-NAFLD population increased the relationship between ANGPTL8 (OR=2.713, 95% CI 1.494-4.926 P=0.001), resistin (OR=4.248, 95% CI 2.260-7.987 P<0.001)and DN. The area under the curve (AUC) on receiver operating characteristic (ROC) analysis of the combination of ANGPTL8 and resistin was 0.703, and the specificity was 70.4%. These data were also increased in non-NAFLD population, as the AUC (95%CI) was 0.756, and the specificity was 91.2%. Conclusion: This study highlights a close association between ANGPTL8, resistin and DN, especially in non-NAFLD populations. These results suggest that ANGPTL-8 and resistin may be risk predictors of DN.

The Associations of Body Image Perception with Serum Resistin Levels in Highly Trained Adolescent Estonian Rhythmic Gymnasts.

Rhythmic gymnasts (RGs) are more likely to be dissatisfied with their body mass and shape compared to untrained controls (UCs). However, due to the lack of information, the aim of this study was to investigate the associations of body image perception (BIP) with body composition, daily energy consumption and different blood biochemical markers in adolescent RGs compared to UCs. Thirty-three highly trained RG girls and 20 UC girls aged 14-18 years participated in this cross-sectional study. Height, body mass, body composition, energy intake, resting energy expenditure, training volume and different blood biochemical markers were measured. The body attitude test (BAT) was used to evaluate the BIP of the participants. There were no differences in the total BAT scores between the groups. In RGs, the BAT score correlated positively with the serum resistin level (r = 0.35; p = 0.047). A stepwise multiple regression analysis showed that 40.8% of the variability in the BAT score was determined by resistin and BMI. The association of BIP with resistin values was observed only in RGs. In conclusion, our findings add to the increasing evidence that resistin may be a link between BIP and body composition, most likely through fat mass, in adolescent female RGs.

Resistin levels decrease as insulin resistance increases in a Mexican-American cohort.

AIMS: Links between resistin, insulin resistance (IR), and resistin-stimulated cytokine signaling remain unknown in Mexican-Americans. A Mexican-American cohort was examined to determine (1) relationships between circulating resistin and IR, (2) resistin's associations with cytokines and demographic and anthropometric variables, and (3) similar measurements with other adipokines. METHODS: For cross sectional analyses, 953 adults (367 males and 586 females) in the Cameron County Hispanic Cohort (CCHC) were stratified into three groups: normal glucose tolerance, prediabetes, and diabetes mellitus. Differences in resistin and other adipokine levels were examined using linear regression via unadjusted model (Model 1), model adjusted for cytokines (Model 2), and model further adjusted for demographic and anthropometric variables (Model 3). RESULTS: HOMA-IR increased with worsening glucose tolerance (p < 0.0001). In all models, resistin significantly decreased as glucose tolerance deteriorated. Model 3 resistin was positively associated with IL-1ß (p = 0.0252) and IL-8 (p < 0.0001), inversely associated with TNF-α (p = 0.0352), but nonsignificantly associated with IL-6 (p = 0.8671). Model 3 leptin was significantly lower in diabetes mellitus compared to other groups (p < 0.005) and positively associated with female sex (p < 0.0001), age (p = 0.024), and BMI (p < 0.0001), without significant cytokine associations. Adiponectin displayed no significant associations with glucose tolerance, but was significantly associated with sex, BMI, and lipids (Model 3). CONCLUSIONS: Resistin unexpectedly decreased as IR increased while supporting evidence of a resistin-stimulated cytokine pathway in this Mexican-American cohort. Leptin fell with elevated IR after adjusting for cytokines, demographic and anthropometric variables. Adiponectin nonsignificantly decreased as IR increased while showing significant associations with sex, BMI, and lipids.

Protective effects of p-coumaric acid against high-fat diet-induced metabolic dysregulation in mice.

p-Coumaric acid (PC), a naturally occurring phytochemical, possesses antioxidant and anti-inflammatory properties; however, the mechanisms underlying its protective effects against obesity-related metabolic dysfunction are largely unknown. Here, we treated C57BL/6J mice to a high-fat diet (HFD) with or without PC (10 mg/kg body weight/day) for 16 weeks to determine whether PC ameliorates HFD-induced obesity, insulin resistance, inflammation, and non-alcoholic fatty liver disease (NAFLD). We found no significant differences in food intake and body weight between the groups. However, PC-treated mice showed significantly lower white adipose tissue (WAT) weight, adipocyte size, and plasma leptin level, which were associated with decreased lipogenic enzyme activity and mRNA expression of their genes in the epididymal WAT. Moreover, hepatic lipogenic enzymes activities and expression of their genes and proteins were decreased with concomitant increases in hepatic fatty acid oxidation and mRNA expression of its gene; fecal lipid excretion was significantly increased, resulting in decreased liver weight, hepatic lipid levels, lipid droplet accumulation, and plasma aspartate aminotransferase and lipid levels. Additionally, PC-treated mice showed lower fasting blood glucose, plasma resistin, and MCP-1 levels, HOMA-IR, and mRNA expression of inflammatory genes in the epididymal WAT and liver. Our findings reveal potential mechanisms underlying the action of PC against HFD-induced adiposity, NAFLD, and other metabolic disturbances.

Evaluation of the frequency of RETN c.62G>A and RETN c.-180C>G polymorphisms in the resistin coding gene in girls with anorexia nervosa.

INTRODUCTION: Anorexia nervosa (AN) is a serious psychosomatic syndrome, classified as an eating disorder. AN patients strive to lose weight below the normal limits defined for a specific age and height, achieving their goal even at the expense of extreme emaciation. AN has a multifactorial aetiology. Genetic factors are believed to be significant in the predisposition to the development of AN. In girls suffering from AN significantly lower levels of resistin (RES) in blood serum are observed as compared to healthy girls. These differences may lead to a thesis that functional genetic polymorphisms in RES coding genes can be responsible for this phenomenon. In our pilot study we demonstrated significant differences in the distribution of genotypes in the locus RETN c.-180C>G of the RES gene in 67 girls with AN and 38 healthy girls. It seems reasonable to compare the frequency of polymorphisms of RETN c.62G>A and RETN c.-180C>G in the RES gene in girls with AN and in healthy subjects in a bigger cohort and to analyse correlations between individual variants of the polymorphisms referred to above and the RES levels in blood plasma. MATERIAL AND METHODS: The study covered 308 girls with the restrictive form of AN (AN) and 164 healthy girls (C) (aged 11-19 years). The RES levels in blood serum were determined by means of the ELISA method on a Bio-Vendor machine from LLC (Asheville, North Carolina, USA). The DNA isolation was carried out by means of Genomic Mini AX BLOOD (SPIN). The PCR reaction was carried out on a ThermoCycle T100 thermocycler. 80-150 ng of the studied DNA and relevant F and R starters were added to the reaction mixture. The reaction products were subjected to digestion by restriction enzymes and separated on agarose gels (RFLP). RESULTS: The average RES level in blood serum in the AN group was significantly lower (p < 0.0001) than in the C group. The distribution of genotypes in the locus RETN c.62 of the RES gene was similar in both groups. A significant difference was demonstrated in the distribution of genotypes in the polymorphic site RETN c.-180 of the RES gene between AN and C (p = 0.0145) and in the distribution of the C and G alleles in the locus RETN c.-180 (p < 0.0001). The C allele occurred significantly more frequently than the G allele in the C group as compared to the AN group. In all the study subjects jointly (AN and C) a significant positive correlation between the blood RES levels on one hand and the body mass (r = 0.42; p < 0.0001) and BMI (r = 0.61; p< 0.0001) on the other was observed. There was no correlation between the concentration of RES in blood serum and the distribution of genotypes in the loci of the resistin gene referred to above. CONCLUSIONS: The CG genotype in the locus RETN c.-180 C>G of the RES gene may constitute one of the factors predisposing to the development of AN in girls. The genotype in the loci RETN c.62 G>A and RETN c.-180 C>G of the resistin gene has no influence on the levels of this hormone in blood in AN patients.