Changes in adipokine indicators depending on A1166C polymorphism of the angiotensin II type 1 receptor gene as a predictor of the arterial hypertension.

Objective. Genetic factors substantially contribute to the development and duration of arterial hypertension. The study of the A1166C polymorphism of the angiotensin II type 1 receptor gene (AGTR1) in arterial hypertension is an auspicious area for assessing the relationship between heredity, hypertension development, and adipokines, but it still remains debatable. The purpose of the current study was to investigate serum adipokines levels depending on the AGTR1 A1166C polymorphism. Methods. A total of 86 patients with arterial hypertension were examined, who underwent the evaluation of the allelic A1166C polymorphism of AGTR1 by polymerase chain reaction with electrophoretic detection and determination of serum adipokines levels using enzyme-linked immunosorbent assay. Results. In the group of patients with arterial hypertension, a significant increase in serum adipokines (resistin, adiponectin, and leptin) levels was found against the background of a decrease in the antianorexic hormone ghrelin with a predominance of CC genotype carriers compared with AA genotype carriers of the AGTR1. A statistically significant decrease in ghrelin and an increase in serum adipokines (resistin, adiponectin, and leptin) in CC genotype carriers compared with AA genotype carriers of the AGTR1 were found suggesting that CC genotype carriers may be predictors of the development of arterial hypertension in our patients. Conclusions. Statistically significant decrease in ghrelin and increase in serum adipokines (resistin, adiponectin, and leptin) were found in CC genotype carriers compared with AA genotype carriers of the AGTR1, which suggests that carriers of the CC genotype are predictors of the arterial hypertension development in our patients.

Comparative Effects of Gymnema sylvestre and Berberine on Adipokines, Body Composition, and Metabolic Parameters in Obese Patients: A Randomized Study.

Gymnema sylvestre (GS) and berberine (BBR) are natural products that have demonstrated therapeutic potential for the management of obesity and its comorbidities, as effective and safe alternatives to synthetic drugs. Although their anti-obesogenic and antidiabetic properties have been widely studied, comparative research on their impact on the gene expression of adipokines, such as resistin (Res), omentin (Ome), visfatin (Vis) and apelin (Ap), has not been reported. METHODOLOGY: We performed a comparative study in 50 adult Mexican patients with obesity treated with GS or BBR for 3 months. The baseline and final biochemical parameters, body composition, blood pressure, gene expression of Res, Ome, Vis, and Ap, and safety parameters were evaluated. RESULTS: BBR significantly decreased (p < 0.05) body weight, blood pressure and Vis and Ap gene expression and increased Ome, while GS decreased fasting glucose and Res gene expression (p < 0.05). A comparative analysis of the final measurements revealed a lower gene expression of Ap and Vis (p < 0.05) in patients treated with BBR than in those treated with GS. The most frequent adverse effects in both groups were gastrointestinal symptoms, which attenuated during the first month of treatment. CONCLUSION: In patients with obesity, BBR has a better effect on body composition, blood pressure, and the gene expression of adipokines related to metabolic risk, while GS has a better effect on fasting glucose and adipokines related to insulin resistance, with minimal side effects.

The role of adipokines in the pathogenesis of psoriasis - a focus on resistin, omentin-1 and vaspin.

BACKGROUND: Psoriasis is a chronic immune-mediated skin condition with several types of manifestation, including psoriatic arthritis. In recent years, studies have demonstrated multiple molecules and mechanisms that play important roles in the pathophysiology of psoriasis. Studies have been conducted to determine the role of adipokines, bioactive peptides secreted by the adipose tissue, in the pathogenesis of inflammatory diseases. These studies have shown that adipokines are dysregulated in psoriasis and their abnormal expression profile could contribute to the inflammatory mechanisms observed in psoriasis. AREAS COVERED: In this review, we discuss the immunomodulatory features of resistin, omentin-1, and vaspin, and discuss their potential involvement in the pathogenesis of psoriasis. EXPERT OPINION: The adipokines resistin, omentin, and vaspin appear to be promising therapeutic targets in psoriasis. It is important to seek to block the action of resistin, either by blocking its receptors or by blocking its systemic effects with antibodies. In the case of omentin and vaspin, substances that are receptor mimetics of these adipokines should be sought and studies conducted of their analogues for the treatment of psoriasis. To introduce these therapies into clinical practice, multicentre clinical trials are required to confirm their efficacy and safety after initial studies in animal models.

Resistin Gene Promoter -420C>G (rs1862513) and +299 G>A (rs3745367) Polymorphisms in Psoriasis.

BACKGROUND: The pro-inflammatory adipokine resistin is known to be related to obesity, insulin resistance, and inflammation. Resistin's significance in the etiology of inflammatory illnesses, such as psoriasis, is explored herein. We examined the link between resistin gene polymorphisms (-420 C>G and +299 G>A) and psoriasis in the Turkish population. METHODS: In this study, we examined 107 patients with psoriasis and 103 healthy controls. Resistin -420 C>G (rs1862513) and +299 G>A (rs3745367) gene polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: In patients with psoriasis, the frequency of the resistin -420 CG genotype was meaningfully lower than in the controls. In comparison with the controls, the resistin +299 GA genotype and A allele frequencies were significantly higher. The Resistin -420 CG genotype significantly reduced the risk of psoriasis incidence, while the resistin +299 GA genotype and A allele were found to be associated with a higher risk of psoriasis. CONCLUSIONS: In the Turkish community, resistin gene polymorphisms at -420 C>G and +299 G>A may exert an important influence on psoriasis etiology and susceptibility.

Resistin and omentin in breast cancer: A systematic review and meta-analysis.

Breast cancer (BC) is the most frequently diagnosed cancer and a leading cause of cancer-related mortality among women globally. Resistin, omentin and ghrelin, adipokines involved in inflammation and metabolic regulation, have been implicated in cancer development, yet their associations with BC remain unclear. This systematic review and meta-analysis aimed to elucidate the relationships between resistin, omentin, and ghrelin concentrations and BC, while exploring potential moderators such as body mass index (BMI) and menopausal status. A comprehensive search of electronic databases up to 13 May 2024 identified studies comparing resistin and omentin, but not ghrelin, concentrations in BC patients and healthy controls. Standardized mean differences (SMDs) were calculated using random-effects models, and meta-regression and subgroup analyses were performed to investigate sources of heterogeneity. Analysis of 11 studies showed that BC patients exhibited significantly higher resistin concentrations compared to controls, with a pooled SMD of 2.05 (95 % CI 1.24 to 2.86, p < 0.001). Meta-regression indicated that BMI significantly moderated the resistin-BC association (p = 0.003). In contrast, omentin concentrations presented a complex picture, with a pooled SMD of -0.27 (95 % CI -1.39 to 0.84, I^2 = 96.2 %, p < 0.001), indicating substantial heterogeneity and inconclusive results, whereas only one study investigated ghrelin. Our findings support a significant association between elevated resistin concentrations and BC, suggesting a potential role of resistin in BC pathophysiology. The data on omentin and ghrelin remain inconclusive, warranting further investigation. Future research should focus on large, longitudinal studies with standardized methodologies to validate these findings and clarify the role of adipokines in BC.

Association of selected adipokines with vitamin D deficiency in children with inflammatory bowel disease.

BACKGROUND: Adipose tissue is significantly involved in inflammatory bowel disease (IBD). Vitamin D can affect both adipogenesis and inflammation. The aim of this study was to compare the production of selected adipokines, potentially involved in the pathogenesis of IBD - adiponectin, resistin, retinol binding protein 4 (RBP-4), adipocyte fatty acid binding protein and nesfatin-1 in children with IBD according to the presence of 25-hydroxyvitamin D (25(OH)D) deficiency. METHODS: The study was conducted as a case-control study in pediatric patients with IBD and healthy children of the same sex and age. In addition to adipokines and 25(OH)D, anthropometric parameters, markers of inflammation and disease activity were assessed in all participants. RESULTS: Children with IBD had significantly higher resistin levels regardless of 25(OH)D levels. IBD patients with 25(OH)D deficiency only had significantly lower RBP-4 compared to healthy controls and also compared to IBD patients without 25(OH)D deficiency. No other significant differences in adipokines were found in children with IBD with or without 25(OH)D deficiency. 25(OH)D levels in IBD patients corelated with RBP-4 only, and did not correlate with other adipokines. CONCLUSIONS: Whether the lower RBP-4 levels in the 25(OH)D-deficient group of IBD patients directly reflect vitamin D deficiency remains uncertain. The production of other adipokines does not appear to be directly related to vitamin D deficiency.

The rs1862513 promoter variant of resistin gene influences susceptibility to nonalcoholic fatty liver disease.

OBJECTIVES: Nonalcoholic fatty liver disease is the term used for a range of conditions in which fat builds up in the liver and exceeds 5% of hepatocytes without inordinate alcohol intake or other causes of lipid accumulation. Regarding the fact that insulin resistance and obesity play key roles in the pathogenesis of nonalcoholic fatty liver disease, as well as the connection between resistin and these metabolic diseases, the association between nonalcoholic fatty liver disease and a resistin gene (RETN) polymorphism was examined. METHODS: In this genetic case-control association study, 150 biopsy-proven nonalcoholic fatty liver disease patients and 154 controls were enrolled and genotyped for the RETN rs1862513 (-420C>G) gene polymorphism using PCR-RFLP method. RESULTS: The -420C>G genotype frequency distributions in both groups were consistent with Hardy-Weinberg equilibrium (HWE; p>0.05). The carriers of the RETN -420C>G "CC" genotype compared with the "GG" genotype occurred less frequently in the cases with nonalcoholic fatty liver disease than in the controls, and the difference remained significant even after adjustment for confounding factors (p=0.030; OR=0.47, 95%CI=0.36-0.93). Interestingly, the RETN -420C>G "C" allele was also associated with a decreased risk for nonalcoholic fatty liver disease too (p=0.042; OR=0.72, 95%CI=0.53-0.95). CONCLUSION: We found for the first time an association between biopsy-proven nonalcoholic fatty liver disease and RETN -420C>G promoter polymorphism. The carriers of the RETN -420C>G "CC" genotype had a 53% decreased risk for nonalcoholic fatty liver disease. Our findings, however, need to be corroborated by further studies.

Adipokines-A Cohort Prospective Study in Children with Severe Burns.

Burns generate every year an important burden of morbidity, being a major global public health problem through prolonged hospitalization, complications, and increased mortality. This study's purpose was to evaluate the serum levels of three adipokines and to establish significant correlations with other circulating molecules and with some clinical parameters. We evaluated 32 children with severe burns (over 25% total burned surface area-TBSA) at 48 h, day 10, and day 21 post burn, and 21 controls. The serum levels of adiponectin, resistin, leptin, tumor necrosis factor-α (TNF-α), plasminogen activator inhibitor-1 (PAI-1), and C-reactive protein (CRP) (among nine other biochemical parameters) were detected by Multiplex technique. Significant statistical differences were obtained for resistin and leptin compared to the control group, in different moments of measurements. Adiponectin serum levels presented statistically significant correlations with hot liquid mechanism of burn, the Revised Baux score, TBSA, resistin, PAI-1, CRP, TNF-α, and triglycerides (TGLs) serum levels. Resistin serum levels presented statistically significant correlations with adiponectin, CRP, PAI-1, leptin, and TNF-α. Additionally, we found statistically significant correlations between leptin serum levels and length of hospitalization, TNF-α, resistin, adiponectin, and PAI-1 serum levels. In severely burned children, adiponectin, resistin, and leptin specifically correlate with clinical parameters and with proteins involved in the systemic inflammatory response and the hypermetabolic response.

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.

The effect of different high-intensity interval training protocols on cardiometabolic and inflammatory markers in sedentary young women: A randomized controlled trial.

Few studies have reported the cardiovascular health effects of different high-intensity interval training (HIIT) protocols among sedentary young women. We investigated the impact of a traditional HIIT programme and a high-intensity circuit training (HICT) programme on lipid profiles and inflammatory cytokine levels in sedentary young women. Forty-two women were randomly assigned to HICT (body weight-based training), HIIT (cycling-based training), or control groups (n = 14 each). HICT and HIIT participants completed an 8-week training programme of three sessions per week. Total cholesterol (TC), triglyceride, high- and low-density lipoprotein, leptin, resistin, tumour necrosis factor-alpha (TNF-α), interleukin-8, and interferon-gamma levels were measured before and after the intervention. Post-intervention, TC and leptin were decreased in the HICT group. The HICT group also demonstrated increased lean mass, upper and lower limb strength, and balance, while the HIIT group displayed improved lower limb strength. Additionally, the control group showed significant increases in triglyceride levels, weight, body mass index, and fat mass. In conclusion, although both HICT and HIIT interventions showed improvements in cardiovascular health and physical fitness, participants in the HICT group experienced more health benefits.

Inflammatory markers and body mass index amoung hispanic children.

BACKGROUND AND OBJECTIVES: Body mass index (BMI) is inversely proportional with adiponectin levels among adults, while insulin, C-reactive protein (CRP), interleukin 6 (IL-6), resistin and tumor necrosis factor-alpha (TNF-α) have been linked with elevated BMI. The role and relation of these biomarkers with BMI among a Hispanic pediatric population are less known. Thus, the objective of this study was to examine the association of inflammatory markers with the odds of overweight/obesity while controlling for several sociodemographic factors among a Hispanic youth population in Northeast Tennessee. METHODS: Height, weight, demographic information, and blood samples were collected from 107 Hispanic children aged 2 to 10 years recruited at a large community health center in 2015-2016 in Northeast Tennessee. Data for this research were accessed and analyzed in 2022. Multivariable logistic regression was conducted to assess the relations between adiponectin, insulin, resistin, CRP, TNF-α, and IL-6, and overweight/obesity vs. having a healthy (normal) weight. RESULTS: Adiponectin levels were significantly lower among overweight/obese Hispanic children (p = 0.0144) compared to healthy weight children. The odds of overweight/obesity decreased by 4% for every one-unit increase in serum adiponectin. Insulin levels were significantly higher among overweight/obese Hispanic children compared to healthy weight children (p = 0.0048). The odds of overweight/obesity increased by 7% for every one-unit increase in serum insulin. Resistin, IL-6, TNF-α, and CRP were not significantly associated with overweight/obesity in this population. CONCLUSION: Adiponectin behaves similarly in Hispanic youth as it does in other pediatric populations, possibly making it a valuable marker when examining metabolic health status in this population.

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.

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.

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.

Association of adipokine levels with obesity in periodontal health and disease: A systematic review with meta-analysis and meta-regression.

This study aimed to investigate the levels of serum, gingival crevicular fluid (GCF), and salivary adipokines and their possible relationship with periodontitis and obesity. An electronic search was conducted in the following databases: PubMed/ Medline, Scopus, and EBSCOhost through February 2023. Two independent reviewers screened the titles, abstracts, and full text of all the studies. Studies comparing the levels of adipokines in GCF, serum, and/or saliva in subjects with obesity and periodontitis (group 1), subjects with normal weight and periodontitis (group 2), and subjects with obesity and gingival health (group 3) were included. Meta-analyses and meta-regression were performed on the data from included studies. Seventeen studies with study participants ranging from 30 to 120 were included with subjects in each group ranging from 10 to 40. There was a significant increase in levels of serum TNF-α, leptin, IL-6, and CRP between groups 1 and 2 (p < .05). In GCF, TNF-α and resistin levels were significantly higher (p < .05) in Group 1 vs. 2. Serum level of leptin was higher for group 1 vs. 3 (p < .05). Meta-regression analysis revealed that the obesity definition (body mass index (BMI) cut-off value >25 or >30) was significant for serum resistin (p < .05) and GCF resistin (p < .05) between group 1 and 2. The current analysis indicates that both periodontitis and obesity can modulate the pro-inflammatory cytokines at systemic and local levels. This bidirectional interaction of periodontitis and obesity via the inflammation pathway seems likely plausible. Further studies are required to elucidate this mechanism in more detail.

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.

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.

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.