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• Wheat germ improved markers of glucose homeostasis in overweight adults. • Wheat germ reduced the pro-inflammatory adipokine, resistin. • Gut microbiota and gut integrity markers were unaffected by wheat germ. Wheat germ (WG), a by-product of flour milling, is rich in bioactive substances that may help improve health complications associated with increased adiposity. This study investigated the effects of WG on gut health, metabolic, and inflammatory markers in adults classified as overweight. We hypothesized that WG, because of its many bioactive components, would improve gut health and metabolic, and inflammatory markers in overweight adults. Forty adults (18–45 years old) and with a body mass index between 25 and 30 kg/m2 participated in this single-blinded randomized controlled pilot study. Participants consumed the study supplements containing 30 g of either cornmeal (control, CL) or WG daily for 4 weeks. Primary outcome variables were gut health markers including gut microbiota, gut integrity markers, and fecal short-chain fatty acids, whereas secondary outcome variables included metabolic and inflammatory parameters assessed at baseline and at the end of supplementation. Thirty-nine participants (n = 19 and 20 for CL and WG group, respectively) completed the study. The genus Faecalibacterium was significantly higher in the WG group compared to CL post-supplementation but no significant changes in other gut health markers, short-chain fatty acids, inflammatory markers, and lipid profiles were observed. Compared with baseline, WG improved markers of glucose homeostasis including insulin (P =.02), homeostatic model assessment of insulin resistance (P =.03), glycated hemoglobin (P =.07), and the pro-inflammatory adipokine, resistin (P =.04). However, these parameters after intervention were not different with control. Our findings suggest that WG supplementation have modest effects on gut health but may provide an economical option for individuals to improve glycemic control. Daily consumption of 30 g of wheat germ supplement for 4 weeks by adults classified as overweight maintained the bacterial genus Faecalibacterium and improved several markers of glucose homeostasis including insulin, HOMA-IR, and HbA1c, and reduced the pro-inflammatory adipokine, resistin. Abbreviations: HbA1c, glycated hemoglobin; HOMA-IR, homeostatic model assessment of insulin resistance. [Display omitted] [ABSTRACT FROM AUTHOR]

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. 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. 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. [ABSTRACT FROM AUTHOR]

Polymorphisms in genes of leptin-melanocortin and insulin pathways have been associated with obesity and type 2 diabetes. We hypothesized that polymorphisms in IRS1, IRS2, MC3R , and MC4R influence metabolic and inflammatory markers and food intake composition in Brazilian subjects. This exploratory pilot study included 358 adult subjects. Clinical, anthropometric, and laboratory data were obtained through interview and access to medical records. The variants IRS1 rs2943634 A˃C, IRS2 rs1865434 C>T, MC3R rs3746619 C>A, and MC4R rs17782313 T>C were analyzed by real-time polymerase chain reaction. Food intake composition was assessed in a group of subjects with obesity (n = 84) before and after a short-term nutritional counseling program (9 weeks). MC4R rs17782313 was associated with increased risk of obesity (P =.034). Multivariate linear regression analysis adjusted by covariates indicated associations of IRS2 rs1865434 with reduced low-density lipoprotein cholesterol and resistin, MC3R rs3746619 with high glycated hemoglobin, and IRS1 rs2943634 and MC4R rs17782313 with increased high-sensitivity C-reactive protein (P <.05). Energy intake and carbohydrate and total fat intakes were reduced after the diet-oriented program (P <.05). Multivariate linear regression analysis showed associations of IRS2 rs1865434 with high basal fiber intake, IRS1 rs2943634 with low postprogram carbohydrate intake, and MC4R rs17782313 with low postprogram total fat and saturated fatty acid intakes (P <.05). Although significant associations did not survive correction for multiple comparisons using the Benjamini-Hochberg method in this exploratory study, polymorphisms in IRS1, IRS2, MC3R , and MC4R influence metabolic and inflammatory status in Brazilian adults. IRS1 and MC4R variants may influence carbohydrate, total fat, and saturated fatty acid intakes in response to a diet-oriented program in subjects with obesity. Clinical, anthropometric, and laboratory data were obtained from 358 Brazilian adult subjects. IRS1 rs2943634, IRS2 rs1865434, MC3R rs3746619, and MC4R rs17782313 polymorphisms were evaluated. Food intake composition was assessed in 84 subjects with obesity before and after a short-term nutritional counseling program. Variants in IRS1, IRS2, MC3R , and MC4R influence metabolic and inflammatory status. IRS1 and MC4R variants may influence carbohydrate, total fat, and saturated fatty acids intakes in response to a diet-oriented program. Abbreviations: HbA1c, glycated hemoglobin; hsCRP, high-sensitivity C-reactive protein; InsR, insulin receptor; IRS1, insulin receptor substrate 1; IRS2, insulin receptor substrate 2; LDL-c, low-density lipoprotein cholesterol; LepR, leptin receptor; MC3R, melanocortin receptor 3; MC4R, melanocortin receptor 4; SFA, saturated fatty acids; 9w, 9 weeks. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: In current intensive care treatment, some patients with severe burns cannot be saved due to progressive organ failure. Further investigation of the pathogenesis of severe burns is needed to improve the mortality rate. In burns, inflammatory cytokines form a network that leads to an inflammatory response. Adipocytes secrete physiologically active substances (adipokines). The roles of adipokines have not been completely clarified in burn patients. This study aimed to determine the relation between serial changes of adipokines and clinical course in severely burned patients.Methods: This was a single-center, retrospective, observational study. Patients' blood samples were collected on the day of injury and around 1 week later. Adipokines (adiponectin, angiotensinogen, chemerin, CXCL-12/SDF-1, leptin, resistin, vaspin, visfatin), various inflammatory cytokines, syndecan-1 and C1 esterase inhibitor were measured.Results: Thirty-eight patients were included. Resistin levels were significantly higher in the non-survivors versus survivors on Day 1 after burn injury. Hierarchical clustering analysis showed common clusters on Day 1 and at 1 Week after burn injury (resistin, IL-6, IL-8, IL10 and MCP-1). The correlation coefficient of resistin to SOFA score at 1 Week was significant. Logistic regression analysis showed a significant relation of resistin levels on Day 1 with prognosis; the area under the ROC curve for resistin was 0.801.Conclusions: In the acute phase of burns, resistin was associated with other pro-inflammatory cytokines and was related to the severity and prognosis of major burns. [ABSTRACT FROM AUTHOR]

Irisin is a myokine with a potential role in cardiometabolic diseases, but previous studies have described inconsistencies between serum irisin and physical activity (PA). Our aim was to analyze the relationship between serum irisin and leisure-time PA (LTPA) in a large sample of the general adult population, and secondarily, to evaluate its relationship with two PA-related biomarkers (HDL cholesterol and resistin). A cross-sectional study was nested in the "CDC of the Canary Islands" cohort participants (n = 3827, 18–75 years, 60% women). PA was collected by administering the Minnesota leisure-time physical activity questionnaire, and physical examination and blood tests (irisin, resistin, HDL-cholesterol) were performed. Irisin inversely correlated with BMI (p < 0.001 in women) and resistin (p = 0.038 in women, p = 0.004 in men), and directly with HDL cholesterol (p < 0.001in women). There was a direct association of irisin with leisure-time and energy expenditure in light, moderate and vigorous LTPA, which was stronger in women than men. The distribution of leisure-time and PA variables across irisin quintiles showed a significant trend, except for light LPTA in men. Adjusting for age, sex and BMI, the association of irisin with leisure-time and LTPA variables was stronger than the association of these variables with resistin and HDL cholesterol, reaching the strongest association for irisin with the 80th percentile of time of LTPA (OR = 2.57; 95% CI = 2.00–3.31). There is a direct and independent association between serum irisin levels and LTPA in the general adult population, which is stronger than other biomarkers of PA. Findings on exercise-related irisin support the possibility of irisin health benefits. [ABSTRACT FROM AUTHOR]

The discovery that metabolic alterations often coexist with neurodegenerative conditions has sparked interest in the examination of metabolic regulatory factors as potential modulators of brain health. Here, we examined the role of adipokines (leptin, adiponectin, resistin, and IL6) and insulin on different markers of brain atrophy in participants on the spectrum of Alzheimer's Disease. We included 566 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset with 1063 follow-up time points (average follow-up: one year); and examined the association between metabolic regulatory factors and volumetric MRI values, white matter hyperintensities, and measures of cognitive impairment. Higher leptin, resistin, IL6, and insulin were associated with markers of cerebral atrophy, such as lower total brain volume, or higher ventricular volume. Higher leptin and resistin were also associated with greater impairment in daily life activities. Higher adiponectin was associated with lower ventricle volume. There was no association between adipokines or insulin with white matter hyperintensities. Our findings indicate a co-occurrence between alterations in metabolic regulatory factors and in brain volume along the preclinical to clinical spectrum of Alzheimer's Disease. These results suggest that strategies aimed at promoting metabolic health may positively impact brain health. • Metabolic dysregulations and brain disability often come hand in hand. • We examined the association between adipokines, insulin, and brain atrophy. • Higher leptin, resistin, IL6, and insulin were associated with lower brain volume. • Higher adiponectin was associated with lower ventricular volume. • Our findings suggest that metabolic alterations coexist with worse brain outcomes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

To investigate the blood levels of adipokines in obese patients with endometrial cancer who have and have not undergone omentectomy. Between September 2017 and September 2019, the study recruited 54 patients with endometrial cancer. Measurements were taken of blood levels of human leptin, perilipin-1, adiponectin, adipolin, resistin, visfatin, and estrone preoperatively and postoperatively before adjuvant therapy or at the end of one month. The serum samples were separated by centrifugation for 10 mins at 3,000 revolutions/min, then stored at −80 °C until assay. In this prospective study, a total of 54 endometrial cancer patients were analyzed in two separate groups according to the omentectomy status. Comprehensive staging surgery with omentectomy and without omentectomy was performed in 26 patients and 28 patients, respectively. The age, body mass index, body fat index, waist circumference, and skin thickness values of the patients with and without omentectomy were found to be similar. No statistically significant difference was determined between the patients with and without omentectomy in respect of the blood level of the adipokines measured preoperatively. A strong statistically significant correlation was determined between the pre and postoperative levels of Human Leptin (p = 0.002), perilipin-1(p = 0.001), adipolin (p < 0.001), adiponectin (p < 0.001), resistin (p = 0.001), visfatin (p < 0.001), and estrone (p = 0.004) (r = −0.43, −0.47, 0.75, 0.84, −0.47, - 0.58, −0.41, respectively) Omentectomy affected the postoperative blood levels of adipokines in obese patients with endometrial cancer. As omentectomy may have some positive effects on metabolism in these patients, it may be considered during endometrial cancer surgery due to the possible positive metabolic effects. • The coexistence of endometrial cancer with obesity is common. • Omentectomy changed blood levels of adipokines. • Adipokines have a critical role on the metabolism of glucose or lipid [ABSTRACT FROM AUTHOR]

Here we developed a powerful tool for comprehensive data collection and mapping of molecular and elemental signatures in the Melanoma-bearing Libechov Minipig (MeLiM) model. The combination of different mass spectrometric methods allowed for detail investigation of specific melanoma markers and elements and their spatial distribution in tissue sections. MALDI-MSI combined with HPLC-MS/MS analyses resulted in identification of seven specific proteins, S100A12, CD163, MMP-2, galectin-1, tenascin, resistin and PCNA that were presented in the melanoma signatures. Furthermore, the ICP-MS method allowed for spatial detection of zinc, calcium, copper, and iron elements linked with the allocation of the specific binding proteins. [ABSTRACT FROM AUTHOR]

Aims: Although overweight and obesity are associated with increased risk of atrial fibrillation (AF), the underlying mechanisms are not well characterised. Recent data suggest that this link may be partly due to abnormal adipose tissue-derived cytokines or adipokines. However, this relationship is not well clarified. To evaluate the association between adipokines and AF in a systematic review and meta-analysis.Data Synthesis: PubMed, Embase, and Web of Science Core Collection were searched from inception through 1st March 2021. Studies were included if they reported any adipokine and AF, with their quality assessed using the Newcastle-Ottawa scale. Data were independently abstracted, with unadjusted and multivariable adjusted estimates pooled in a random-effects meta-analysis. Data are presented for overall prevalent or incident AF and AF subtypes (paroxysmal, persistent, or non-paroxysmal AF). A total of 34 studies, with 31,479 patients, were included. The following adipokines were significantly associated with AF in the pooled univariate data - apelin (risk ratio for prevalent AF: 0.05 [0.00-0.50], p = 0.01; recurrent AF: 0.21 [0.11-0.42], p < 0.01) and resistin (incident AF: 2.05 [1.02-4.1], p = 0.04; prevalent AF: 2.62 [1.78-3.85], p < 0.01). Pooled analysis of multivariable adjusted effect size estimates showed adiponectin as the sole independent predictor of AF incidence (1.14 [1.02-1.27], p = 0.02). Moreover, adiponectin was associated with non-paroxysmal AF (persistent AF: 1.45 [1.08-1.94, p = 0.01; non-paroxysmal versus paroxysmal AF: 3.14 [1.87-5.27, p < 0.01).Conclusions: Adipokines, principally adiponectin, apelin, and resistin, are associated with the risk of atrial fibrillation. However, the association is not seen after multivariate adjustment, likely reflecting the lack of statistical power. Future research should investigate these relationships in larger prospective cohorts and how they can refine AF monitoring strategies.Prospero Id: CRD42020208879. [ABSTRACT FROM AUTHOR]

[Display omitted] 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. [ABSTRACT FROM AUTHOR]

• The RETN-CAP1 ligand-receptor pair, which mediated Resistin signaling, was enhanced in monocytes of septic patients when compared to healthy controls. • The signaling of IL-16, mediated by the IL16-CD4 ligand-receptor pair, was enhanced in monocytes of septic shock patients when compared to sepsis patients. • Single-cell transcriptome data revealed monocyte heterogeneity in sepsis progression. Sepsis is a disease characterized by infection-induced multiorgan dysfunction, which can progress to septic shock if not promptly treated. Early identification of sepsis is crucial for its treatment. However, there are currently limited specific biomarkers for sepsis or septic shock. This study aims to identify potential biomarkers for sepsis and septic shock. We analyzed single-cell transcriptomic data of peripheral blood mononuclear cells (PBMCs) from healthy individuals, sepsis and septic shock patients, identified differences in gene expression and cell–cell communication between different cell types during disease progression. Moreover, our analyses were further validated with flow cytometry and bulk RNA-seq data. Our study elucidates the alterations in cellular proportions and cell–cell communication among healthy controls, sepsis, and septic shock patients. We identified a specific augmentation in the Resistin signaling within sepsis monocytes, mediated via RETN-CAP1 ligand-receptor pairs. Additionally, we observed enhanced IL16 signaling within monocytes from septic shock patients, mediated through IL16-CD4 ligand-receptor pairs. Subsequently, we confirmed our findings by validating the increase in CAP-1+ monocytes in sepsis and IL16+ monocytes in septic shock in mouse models. And a significant upregulation of CAP-1 and IL16 was also observed in the bulk RNA-seq data from patients with sepsis and septic shock. Furthermore, we identified four distinct clusters of CD14+ monocytes, highlighting the heterogeneity of monocytes in the progress of sepsis. In summary, our work demonstrates changes in cell–cell communication of healthy controls, sepsis and septic shock, confirming that the molecules CAP-1 and IL16 on monocytes may serve as potential diagnostic markers for sepsis and septic shock, respectively. These findings provide new insights for early diagnosis and stratified treatment of the disease. [ABSTRACT FROM AUTHOR]

Extra-coronary calcification (ECC) is a marker of atherosclerosis and independently associated with cardiovascular disease (CVD). Adipokines may mediate the effect of obesity on atherosclerosis. However, the relationship of adipokines with ECC is not well-established. We examined the associations of leptin, resistin and adiponectin with ECC in a diverse community-based cohort. We performed a cross-sectional analysis of 1897 adults without clinical CVD in the MESA cohort. Serum adipokine levels and non-contrast cardiac CT scans were obtained at Exam 2 or 3 (randomly assigned). ECC was quantified by Agatston score and included calcification of the mitral annulus (MAC), aortic valve (AVC), ascending thoracic aorta (ATAC) and descending thoracic aorta (DTAC). We used multivariable regression to evaluate the associations between leptin, resistin and adiponectin [per 1 SD ln(adipokine] with ECC prevalence (score >0) and extent [ln(score+1)]. The mean age of participants was 65 ± 10 years; 49% women. After adjusting for demographic factors, adiponectin was inversely associated with AVC prevalence and extent; leptin positively associated with MAC prevalence and extent; and resistin positively associated with ATAC prevalence and extent and DTAC extent. After adjustment for BMI and other CVD risk factors, adiponectin remained inversely associated with AVC prevalence, and resistin remained associated with greater ATAC prevalence and extent. Leptin was not associated with measures of ECC after full adjustment. No adipokine was associated with MAC after full adjustment. We identified significant associations between select adipokines and specific markers of ECC. Adipokines may play a role in the development of systemic atherosclerosis. [Display omitted] • Adiponectin, resistin, and leptin levels are dysregulated in obese individuals. • Low adiponectin levels were associated with aortic valve calcification progression. • Higher resistin levels were associated with thoracic aortic calcification progression. • Leptin does not appear to be associated with extra-coronary calcification. • There is complex interplay between obesity, adipokine levels, and atherosclerosis. [ABSTRACT FROM AUTHOR]

To evaluate resistin level in systemic lupus erythematosus (SLE) patients and to assess the relationship with insulin resistance, disease characteristics, inflammatory markers and carotid intima-media thickness (CIMT) as a marker of subclinical atherosclerosis. Thirty adult SLE patients and twenty age and sex-matched control were enrolled. All patients were subjected to history taking, clinical examination and assessment of anthropometric measurements. Laboratory investigations included serum resistin, measures of insulin resistance, highly sensitive C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR) and lipid profile. Carotid duplex was performed for measurement of CIMT. SLE disease activity index (SLEDAI-2k) and damage index were evaluated. The 30 patients were 23 (76.7%) females and 7 (23.3%) males (F:M 3.3:1) with a mean age of 30.9 ± 7.9 years. The disease duration was 4.8 ± 1.8 years. The mean serum resistin in patients was 7.7 ± 2.9 ng/dl and in control was 8.5 ± 5.1 ng/dl (p = 0.8). The ESR and hs-CRP were significantly increased (p < 0.001) and the high-density lipoprotein (HDL) decreased (p < 0.001). The mean CIMT was significantly increased in cases (0.62 ± 0.16 mm) compared to control (0.51 ± 0.11 mm)(p = 0.006). Serum resistin significantly correlated with hs-CRP, HDL and anti-nuclear antibody (p = 0.027, p < 0.001,p = 0.013 respectively). There was no significant correlation between resistin and markers of insulin resistance, SLEDAI-2 k and CIMT. Resistin expression in the serum of patients with SLE was not significantly higher than controls. Although resistin was correlated with two cardiovascular risk factors (HDL-C, hs-CRP), it did not correlate significantly with insulin resistance, disease activity, damage index and CIMT in SLE patients. [ABSTRACT FROM AUTHOR]

Previous studies have reported a link between metabolic parameters and disease activity in rheumatoid arthritis (RA), although the evidence is limited in early RA. We aimed to investigate the relationship between disease activity and adipocytokine levels in subjects with early RA. Forty-seven patients with early RA (symptom duration ≤12 months) were enrolled. Disease activity was determined by DAS28-CRP. Patients were treated with DMARDs according to the EULAR recommendations. Subjects were tested before and five months after treatment. Early RA patients with high disease activity (DAS28-CRP > 4.9) had greater BMI (31.2 ± 6.8 kg/m2 vs. 26.7 ± 4.1 kg/m2; p = 0.006) and higher leptin levels (14.62 ± 15.60 ng/mL vs. 7.82 ± 8.00 ng/mL; p = 0.048). Levels of other adipocytokines were not significantly different. Leptin levels were similar in subjects with mild/moderate disease activity and controls. DAS28-CRP was correlated with leptin (r = 0.303, p = 0.039). Leptin levels decreased significantly after treatment (from 10.86 ± 12.34 ng/mL to 9.22 ± 9.29 ng/mL; p = 0.047) along with insulin levels (from 13.68 ± 21.90 mU/L to 7.09 ± 4.72 mU/L; p = 0.010) and HOMA-IR (from 4.39 ± 9.53 to 1.70 ± 1.38; p = 0.012). HDL cholesterol levels increased (from 41 ± 10 mg/dL48 ± 10 mg/dL; p <0.001). Leptin levels were associated with disease activity in patients with early RA and these levels decreased after treatment with DMARDs. Further research is needed to elicit leptin's role to regulate disease activity in early RA. [ABSTRACT FROM AUTHOR]

Metabolic syndrome is a clustering of metabolic disorder with unclear molecular mechanism. Increasing studies have found that the pathogenesis and progression of metabolic syndrome are closely related to inflammation. Here, we report celastrol, a traditional Chinese medicine, can improve high fat diet-induced metabolic syndrome through suppressing resistin-induced inflammation. Mechanistically, celastrol binds to adenylyl cyclase associated protein 1 (CAP1) and inhibits the interaction between CAP1 and resistin, which restrains the cyclic adenylate monophosphate (cAMP)–protein kinase A (PKA)–nuclear factor kappa-B (NF- κ B) signaling pathway and ameliorates high fat diet-induced murine metabolic syndrome. Knockdown of CAP1 in macrophages abrogated the resistin-mediated inflammatory activity. In contrast, overexpression of CAP1 in macrophages aggravated inflammation. Taken together, our study identifies celastrol, which directly targets CAP1 in macrophages, might be a promising drug candidate for the treatment of inflammatory metabolic diseases, such as metabolic syndrome. In obesity, adipose tissue generates resistin, which binds to CAP1 on macrophages and activates the cAMP–PKA–NF- κ B signaling pathway and promotes proinflammatory cytokines expression. These factors further aggravate inflammation, insulin resistance, and hepatic steatosis. Celastrol ameliorates metabolic syndrome via binding to CAP1 and inhibiting its interaction with resistin. [Display omitted] [ABSTRACT FROM AUTHOR]

Fibrates are widely used in the treatment of dyslipidemia and associated metabolic abnormalities; however, their effects on adipokines are unclear. Aim of the study. This meta-analysis of clinical trials aimed to evaluate the effect of fibrates on circulating adipokine levels. Only randomized controlled trials investigating the impact/effect of fibrate treatment on circulating adipokine levels were included from searches in PubMed-Medline, SCOPUS, ClinicalTrials.gov, Web of Science, and Google Scholar databases. A random effects model and the generic inverse variance method were used for the meta-analysis. Sensitivity analysis was conducted using the leave-one-out method. This meta-analysis of 22 clinical trials showed a significant reduction on/in leptin (WMD: –1.58 ng/mL, 95% CI: –2.96, –0.20, p = 0.02, I2 = 0%), plasminogen activator inhibitor-1 (PAI-1) (WMD: –13.86 ng/mL, 95% CI: –26.70, –1.03, p = 0.03, I2 = 99%), and visfatin (WMD: –1.52 ng/mL, 95% CI: –2.49, –0.56, p = 0.002, I2 = 0%) after fibrate therapy; no significant effect was observed on adiponectin (WMD: –0.69 µg/ml, 95% CI: –1.40, 0.02, p = 0.06, I2 = 83%) and resistin (WMD: –2.27 ng/mL, 95% CI: –7.11, 2.57, p = 0.36, I2 = 0%). The sensitivity analysis was robust only for visfatin, while the effect size was sensitive to one arm for leptin, four for adiponectin, and two for PAI-1. This meta-analysis showed that fibrate treatment significantly improves adipokine levels with a decrease in leptin, PAI-1, and visfatin, suggesting potential additional clinical therapeutic benefits through/of fibrate treatment on adipose tissue. [ABSTRACT FROM AUTHOR]

Considering the role of adipokine on diseases related to metabolic syndrome and even chronic diseases, it seems necessary to investigate effective interventions on these factors. This study aimed to comprehensively investigate the effects of metformin on adipokines. A comprehensive search was conducted in five databases using established keywords. The purpose of this search was to uncover controlled studies that have examined the impact of metformin on adipokines, specifically leptin, adiponectin, and resistin. The random-effects model analysis was used to provide pooled weighted mean difference and 95% confidence intervals. Forty-nine studies were included in this article. The pooled findings showed that that the administration of metformin significantly decreases leptin (WMD: −3.06 ng/ml, 95 % CI: −3.81, −2.30, P < 0.001) and resistin (WMD: −1.27 µg/mL, 95 % CI: −2.22, −0.31, P = 0.009) levels in different populations compared to the control group. However, no significant effect of this antidiabetic drug on adiponectin levels was reported. The results obtained from the subgroup results in the present study also showed that metformin in people with a BMI greater than 30 kg/m2 compared to a BMI ≤ 30 kg/m2 causes a significant decrease in leptin levels and an increase in adiponectin levels. Also, metformin in lower doses (≤1500 mg/day) and younger people (<30 years) causes a significant increase in adiponectin levels. In general, considering the role of adipokines on metabolic disease and even chronic disease, this drug can be used as a potentially useful drug, especially in obese people, to improve these factors. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the possible link between different types of systemic sclerosis-specific antinuclear antibodies, adipokines and endothelial molecules which were recently found to have a pathogenic significance in systemic sclerosis. Serum concentration of adiponectin, resistin, leptin, endothelin-1, fractalkine and galectin-3 were determined in the sera of patients with systemic sclerosis (n ​= ​100) and healthy controls (n ​= ​20) using ELISA. The following associations between antinuclear antibodies and increased serum concentrations were identified: anticentromere antibodies with endothelin-1 (p ​< ​0.0001; mean level in patients 2.21 vs control group 1.31 ​pg/ml), anti-topoisomerase I antibodies with fractalkine (p ​< ​0.0001; 3.68 vs 1.68 ​ng/ml) and galectin-3 (p ​= ​0.0010, 6.39 vs 3.26 ​ng/ml). Anti-RNA polymerase III antibodies were associated with increased resistin (p ​< ​0.0001; 15.13 vs 8.54 ​ng/ml) and decreased adiponectin (p ​< ​0.0001; 2894 vs 8847 ​ng/ml). In systemic sclerosis metabolic and vascular factors may serve as mediators between immunological abnormalities and non-immune driven clinical symptoms. [ABSTRACT FROM AUTHOR]

Obesity is one of the major modifiable risk factors in breast cancer, with obese adipose tissue showing a pathological role in breast cancer development and malignancy via the release of secretory factors, such as proinflammatory cytokines and adipocytokines. The current article focuses on visfatin and resistin, two such adipocytokines that have emerged over the last two decades as leading breast cancer promoting factors in obesity. The clinical association of circulating visfatin and resistin with breast cancer and their biological mechanisms are reviewed, in addition to their role in the context of tumor-stromal interactions in the breast cancer microenvironment. Recent findings have unraveled several mediators of visfatin and resistin that are involved in the crosstalk between breast cancer cells and adipose tissue in the breast tumor microenvironment, including growth differentiation factor 15 (GDF15), interleukin 6 (IL-6), and toll-like receptor 4 (TLR4). Finally, current therapeutics targeting visfatin and resistin and their respective pathways are discussed, including future therapeutic strategies such as new drug design or neutralizing peptides that target extracellular visfatin or resistin. These hold promise in the development of novel breast cancer therapies and are of increasing relevance as the prevalence of obesity-related breast cancer increases worldwide. [ABSTRACT FROM AUTHOR]

• Resistin triggers various intracellular signal transduction pathways upon binding to membrane receptors TLR4 and CAP1. • Serum resistin is a potential biomarker for the diagnosis and prognosis of CAD. • Resistin promotes atherosclerosis progress via multiple mechanisms. Resistin, a cysteine-rich secretory protein, has a pleiotropic role in humans. Resistin usually presents as trimer or hexamer in plasma, and targets specific receptors Toll Like Receptor 4 (TLR4) or Adenylyl Cyclase-Associated Protein 1 (CAP1). Upon binding to TLR4 and CAP1, resistin can trigger various intracellular signal transduction pathways to induce vascular inflammation, lipid accumulation, and plaque vulnerability. These pro-atherosclerotic effects of resistin appear in various cell types, including endothelial cells, vessel smooth muscle cells and macrophages, which cause diverse damages to cardiovascular system from dyslipidemia, atherosclerosis rupture and ventricular remodeling. In this review, we gather recent evidence about the pro- atherosclerotic effects of resistin and highlight it as a candidate therapeutic or diagnostic target for cardiovascular disease. [ABSTRACT FROM AUTHOR]

Objective: Evaluation of serum concentration of leptin, adiponectin, resistin, and MCP-1 in pregnant patients with different types of diabetes mellitus (DM) considering preconception planning and method of DM correction in 11-14th and 30-34th weeks of pregnancy.Study Design: Longitudinal, prospective study included 130 pregnant women divided into the following comparison groups: type 1 DM (T1DM, n = 40), type 2 DM (T2DM, n = 35), GDM (n = 40), and the control group (n = 15). The ELISA method defined the levels of leptin, resistin, adiponectin, and MCP-1 concentration in serum, which was assessed in 11-14th and 30-34th weeks of pregnancy. Statistical analysis was accomplished using SPSS 23.0 and "Prism 8-GraphPad" software.Results: The leptin level in the 1st trimester was the highest in T2DM insulin group compared to the control due to gestational age, hence in the 3rd trimester in all groups its serum concentrations appeared higher than in healthy patients (p = 0.0001). In the 1st trimester leptin levels directly correlated with women's BMI, newborns' weight and macrosomia rate, in the 3rd trimester - with OGTT levels, HbA1c, gestational hypertension, and preeclampsia rates. Resistin levels in the 1st and 3rd trimesters were increased in almost all DM groups compared to the control group (p = 0.0001). The study established direct positive correlation between resistin and HbA1c, birth weight, and preeclampsia. In the 1st trimester, adiponectin demonstrated the lowest levels in T2DM insulin compared to T1DM and the control group (p = 0.0001) while in the 3rd trimester, adiponectin levels declined alongside gestational age in DM patients and all the groups compared to the control group (p < 0.05). Adiponectin negatively correlated with BMI, OGTT levels, and preeclampsia rate. MCP-1 levels in T2DM appeared higher than in T1DM patients and the control group in the 1st trimester, whereas in the 3rd trimester MCP-1 declined, correlating with BMI, preeclampsia and OGTT levels.Conclusion: High rate of adverse perinatal outcomes in diabetic pregnancy might be developed due to more severe metabolic failures and further disturbances of adipokines expression. [ABSTRACT FROM AUTHOR]

Background and Aims: Pediatric obesity associates with both low-grade inflammation and cardiometabolic risk on the population level. Yet on an individual patient level, overweight/obesity does not always equal increased cardiometabolic risk. In this study, we examine whether low-grade inflammation associates with cardiometabolic risk in Danish children, independent of degree of adiposity. We further assess the value of integrating multiple inflammation markers to identify children with very-high cardiometabolic risk profiles.Method and Results: We studied 2192 children and adolescents aged 6-18 years from an obesity clinic cohort and a population-based cohort, in a cross-sectional study design. Anthropometry, blood pressure, pubertal stage and body composition by dual-energy X-ray absorptiometry were assessed, and biomarkers including fasting serum high sensitivity C-reactive protein (hsCRP), white blood cells (WBC), resistin, lipid profile and glucose metabolism were measured. Adjusted correlation analysis and odds ratios were calculated. We found that, independent of degree of adiposity, having high-normal inflammation marker concentrations associated with increased cardiometabolic risk: for girls, hsCRP >0.57-9.98 mg/L (mid/upper tertile) associated with ~2-fold higher odds of dyslipidemia and hepatic steatosis (vs. lower tertile). For both sexes, WBC >7.0-12.4 109/L (upper tertile) associated with 2.5-fold higher odds of insulin resistance. Lastly, children with multiple inflammation markers in the high-normal range exhibited the most severe cardiometabolic risk profile.Conclusion: Low-grade inflammation associates with cardiometabolic risk in children independent of degree of adiposity. The associations vary with sex and inflammation marker measured. Finally, integrating multiple low-grade inflammation markers identifies a very-high-risk subgroup of children with overweight/obesity and may have clinical value. [ABSTRACT FROM AUTHOR]

• Obesity induces alterations in adipose tissue microenvironment. • Adipocytes are dysfunctional with producing excessive adipokines under obese status. • Immune cells display functional alteration under obese status. • Leptin, resistin, TNF-α, osteopontin, SAA, and IL-6 promote obesity and CVD by respective mechanisms. • Adiponectin, omentin and IL-10 improve obesity and CVD by several pathway. Obesity, defined as having a body mass index (BMI) greater than 30 kg/m2, has been verified to be associated with several health problems which are always grouped as metabolic syndrome. However, the underlying pathogenic mechanisms remain unclear. The hallmarks of obesity are dysfunctional changes in adipose tissue and dyslipidemia characterized by elevated serum levels of low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), and reduced serum levels of high density lipoprotein cholesterol (HDL-C). Currently, it is widely accepted that rather than being a reservoir for energy storage, the adipose tissue could also secrete multiple hormones and molecules, named adipokines. Notably, growing evidence has put forward that under obese status, the adipocytes are dysfunctional with excessive secretion of multiple pro-inflammatory adipokines, contributing to a chronic inflammatory reaction and promote the progression of metabolic and cardiovascular complications. Although some adipokines have been shown to be causally linked to various disease processes, the functions of other novel adipokines in modulating diseases are still not elucidated. In this review, we focus on the microenvironment of adipose tissue and how it influences obesity and cardiovascular disorders. We also summarize the role of adipokines in modulating systemic inflammatory responses that contribute to cardio-metabolic disorders. [ABSTRACT FROM AUTHOR]

Background: Synbiotic foods, which combine the action of prebiotics and probiotics along the gastrointestinal tract, can affect inflammatory and glucose-related markers.Objective: The aim of this study was to investigate the effects on inflammatory and glycemia-related markers of a whole-grain pasta containing barley β-glucans and Bacillus coagulans BC30, 6086 in healthy overweight or obese volunteers.Methods: A single-blind, parallel, randomized, placebo-controlled dietary intervention study was carried out. Forty-one healthy sedentary overweight (body mass index [BMI] 25-29.9 kg/m2) and obese (BMI ≥30) volunteers, aged 30-65 y and low consumers of fruit and vegetables, ate 1 serving/d of whole-grain control (CTR) or innovative (INN) pasta for 12 wk and maintained their habitual diets. Biological samples were collected at baseline and every 4 wk for primary (plasma high-sensitivity C-reactive protein [hs-CRP] and fasting plasma lipid profile) and secondary outcomes (glycemia-related markers, blood pressure, fecal microbiota composition, and body weight). Between (CTR compared with INN) and within (among weeks) group differences were tested for the whole population and for subgroups stratified by baseline values of BMI (≥30) and glycemia (≥100 mg/dL).Results: INN or CTR pasta consumption had no effect on primary and secondary outcomes over time, except for a significant increase in plasma γ-glutamyltransferase (GGT) after 12 wk of CTR pasta consumption. Comparisons between intervention groups revealed differences only at 12 wk: plasma GGT was higher in the CTR group; plasma hs-CRP, plasma LDL/HDL cholesterol ratio, and Bifidobacterium spp. were lower in the INN subgroup of obese volunteers; plasma resistin was lower and Faecalibacterium prausnitzii abundance was higher in the INN subgroup of hyperglycemic volunteers.Conclusions: A daily serving of a synbiotic whole-grain pasta had limited effects on primary and secondary outcomes in the entire group of volunteers but affected glycemia- and lipid-related markers and resistin in a subgroup of healthy obese or hyperglycemic volunteers. This trial was registered at clinicaltrials.gov as NCT02236533. [ABSTRACT FROM AUTHOR]

Resistin acts as an endogenous ligand of Toll-like receptor (TLR)-4 that triggers major inflammatory pathways and mediates inflammatory processes. The role of resistin in osteoarthritis (OA) pathogenesis is unclear. The aim of this study is to describe the longitudinal associations of serum levels of resistin with knee synovitis measures and structural abnormalities in patients with knee OA. A prospective cohort study. Patients (n = 200) with symptomatic knee OA (mean age 63.1 years, range 49-79; female 46.5%) participated. All measures were performed at baseline and 2 years later. Serum resistin was measured using enzyme-linked immunosorbent assay. Infrapatellar fat pad (IPFP) high signal intensity alteration and effusion synovitis were measured from magnetic resonance imaging (MRI). Knee structures including cartilage volume, cartilage defects, and bone marrow lesions (BMLs) were also assessed by MRI semiquantitatively or quantitatively. Linear or logistic mixed effects regression analyses were used in longitudinal analyses. Serum resistin was positively associated with high signal intensity alteration measures of IPFP as well as the presence [relative risk = 1.06, 95% confidence interval (CI) 1.02, 1.10] and volume (β = 0.77, 95% CI 0.01, 1.53) of effusion synovitis in multivariable analyses. Serum levels of resistin were also positively associated with higher tibiofemoral cartilage defect (β = 1.98, 95% CI 0.34, 3.57) and BML scores (β = 3.18, 95% CI 0.99, 5.37) after adjustment for covariates. Higher serum levels of resistin are associated with knee synovitis surrogate measures and structural abnormalities, suggesting that obesity may promote OA not only by increasing weight loading on joints but also by triggering 1 or more inflammatory pathways. [ABSTRACT FROM AUTHOR]

While the role of adipokines in inducing and regulating inflammation is emerging, adipokines have not been studied in acute dengue. Therefore, we sought to determine different adipokine levels in patients with varying severity of acute dengue to understand their role in disease pathogenesis. We determined the levels of leptin, resistin, omentin and adiponectin, by using quantitative ELISA in patients with dengue fever (DF=27) and dengue haemorrhagic fever (DHF=13), at admission (≤ 4 day since onset of illness) (A) and at the time of discharge (day 7 to 8 since onset of illness) (D). Viral loads and the serotype of all samples were quantified using quantitative realtime RT- PCR. The levels of omentin were significantly higher in patients who proceeded to develop DHF compared to DF during admission (p=0.04). In patients with DHF and DF, the omentin levels declined at the time of discharge, which was significant (p=0.04) in patients with DF. The levels of resistin were higher in patients with DHF (median, 1.2, IQR 0.8 to 1.6 pg/ml) compared to those with DF (median 0.75, IQR 0.5 to 1.0 pg/ml) although this was not significant. There was no difference in adiponectin and leptin levels in patients with DF on admission and discharge. In patients who developed DHF, leptin levels increased during these two time points, whereas adiponectin levels decreased. 37/40 (92.5%) individuals were seropositive for DEN-2 and there was no difference in the viral loads in patients who progressed to develop DHF, compared to those who had DF. Omentin is known to be upregulated by type 2 cytokines and induce production of MCP-1. Resistin has shown to induce many proinflammatory cytokines. Therefore, it would be important to further investigate the possible role of these adipokines in dengue disease pathogenesis. [ABSTRACT FROM AUTHOR]

Inflammatory is one of the main cause of aortic valve stenosis (AS), so discovering novel biomarkers for the targeted therapy of inflammation could be an attractive strategy in AS prevention. The objectives of our study were to clarify the modulatory role of resistin and silent information regulator 1 (SIRT1) before and after surgery and also to evaluate the therapeutic effects of resveratrol. Nineteen AS patients and 15 healthy subjects were studied as the case and control groups, respectively. Peripheral blood mononuclear cells (PBMCs) were isolated and cultured to determine the levels of resistin and SIRT1 and the effects of resveratrol on them. Significant increase in resistin expression was observed in the patients compare to the control (p ≤0.01), and this upregulation was augmented 72 h following surgery (p ≤0.01). The SIRT1 expression decreased in the AS group compare to the control but this reduction was not significant. Aortic valve replacement caused a higher decrease in the protein (p ≤0.01) and mRNA level (p ≤0.05) of SIRT1. Resveratrol in the AS group significantly diminished the resistin level (p ≤0.05) but increased the SIRT1 level (p ≤0.001). In our patients with AS, the resistin level was increased, whereas the expression of SIRT1 was reduced and surgery augmented these alterations. Resveratrol improved inflammation in the PBMCs of the patients through the SIRT1/resistin pathway. These findings suggest that pharmacological therapy with resveratrol might be a novel approach to alleviating inflammation in patients with AS. [ABSTRACT FROM AUTHOR]

As the inflammatory regulators, Resistin-like molecule β (RELMβ) and Resistin might be potential biomarkers of necrotizing enterocolitis (NEC), while thrombocytopenia is often related to the severity of NEC, clinical observation suggests that thrombocytopenia might be an early biomarker of NEC. The aim of this study was to evaluate whether RELMβ, Resistin and thrombocytopenia could be biomarkers for early diagnosis of NEC in preterm infants. From January 2016 to March 2018, twenty-nine NEC preterm infants who were diagnosed with NEC (Bell's stage ≥Ⅱ) by two independent neonatologists and twenty-nine non NEC preterm infants at neonatal intensive care unit in our hospital were enrolled in this case-control study. Preterm infants with a history of serious infections (sepsis, pneumonia), asphyxia, and congenital malformations were excluded from the study. The plasma RELMβ and Resistin were evaluated by enzyme linked immunosorbent assay (ELISA) and serum platelet levels were measured directly by ordinary light microscope at the diagnosis of NEC (Bell's stage ≥Ⅱ). Plasma RELMβ levels in NEC group were significantly higher than control group (P < 0.05). The optimal cut-off value of RELMβ determined by receiver operating characteristic curve (ROC) was 378.3 ng/L. The overall estimates for sensitivity and specificity of high RELMβ concentrations in the detection of neonatal NEC were 71.4% and 91.7%, respectively. No significant difference was found in plasma Resistin levels between two groups (P > 0.05). If platelet level was less than 157 × 109/L, the sensitivity and specificity were 69.34% and 82.87%, respectively. Interestingly, the combination of RELMβ and thrombocytopenia increased sensitivity and specificity to 82.89% and 93.21%, respectively. The combination of RELMβ and thrombocytopenia was a reliable biomarker for the early diagnosis of NEC in this study with 82.89% sensitivity and 93.21% specificity, respectively. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVDs) are major causes of morbidity and mortality in systemic lupus erythematosus (SLE) patients. Resistin is an inflammatory adipocytokine associated with insulin resistance and an increased risk of CVD. To study the possible role of resistin (RETN) +299A>G and +62G˃A gene polymorphisms in the development of CVDs among Egyptian SLE patients and their impact on cardio metabolic risk and disease activity. +299A>G and +62G˃A genes polymorphisms were assessed in 140 patients and 100 controls by polymerase chain reaction (PCR). The carotid intima-media thickness (CIMT) was measured. SLE disease activity index (SLEDAI) was assessed. Serum resistin, homeostasis model assessments (HOMA-IR and HOMA-β), fibrinogen and homocysteine were measured. The mean age of patients was 31.1 ± 7.6 years and disease duration 5.4 ± 2.5 years. Serum resistin was significantly increased in patients (4.9 ± 0.2 ng/ml) compared to control (3.02 ± 0.9 ng/ml) (p < 0.001). Serum resistin significantly correlated with uric acid (p < 0.001), homocysteine (p < 0.001), fibrinogen (<0.001) and SLEDAI (p < 0.001). AA genotypes and A allele +299G>A were significantly higher in patients than control (37.9% vs 10% and 63.6% vs 33.5%; p < 0.001). Serum resistin, CIMT, uric acid, fibrinogen and homocysteine was significantly higher in +299G>A GA and AA patients compared to GG (p < 0.001) and HOMA-β decreased (p < 0.001). HOMA-β, fibrinogen and uric acid were independently correlated with resistin (p < 0.001). Resistin +299G/A gene polymorphisms especially the AA genotype and A allele may play an important role in pathogenesis and activity of SLE as well as susceptibility to develop CVD in Egyptian population. [ABSTRACT FROM AUTHOR]

Abstract Interactions among cytokines have important roles in the inflammatory processes underlying Guillain-Barré syndrome (GBS). Resistin and high mobility group box 1 (HMGB1) are involved in many inflammatory processes. This study examined 51 GBS patients, and found that serum resistin levels were elevated in 51 patients with GBS and correlated with HMGB1 levels. In vitro, resistin induced the release of HMGB1, interleukin (IL)-1β, and IL-6 in THP-1 macrophages. This process was dependent on activation of p38 mitogen-activated protein kinase and NF-κB signaling pathways. These results suggest that signaling between resistin and HMGB1 might be a potential therapeutic target in GBS. Graphical abstract Unlabelled Image Highlights • Cytokine interactions affect the pathogenesis of Guillain-Barré syndrome (GBS). • Resistin and high mobility box 1 (HMGB1) are involved in inflammatory processes. • Serum resistin levels, correlated with HMGB1 levels, are elevated in GBS patients. • In THP-1 macrophages, resistin induced the release of HMGB1, IL-1β, and IL-6. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) is characterized as a cluster of metabolic disorder including increased blood pressure, elevated blood glucose level, high cholesterol level and visceral fat obesity. Polypeptide hormones such as adiponectin and resistin play a significant role in glucose and lipids metabolism, liver and pancreas function. This study aimed to investigate the relationship between serum adiponectin and resistin with MetS criteria among Temiar subtribe in Kuala Betis. This cross sectional study involved 123 subjects from Temiar subtribe in Kuala Betis, Gua Musang, Kelantan. MetS criteria were measured according to standard protocol by modified National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) guideline. Anthropometric and biochemical measurements were performed including serum adiponectin and resistin for every study subjects. Serum adiponectin was significantly lower in MetS subjects (7.98 ± 5.65 ng/ml) but serum resistin was found to be significantly higher in MetS subjects (11.22 ± 6.34 ng/ml) compared to non-MetS subjects with p < 0.001 and p = 0.002 respectively. Serum adiponectin was negatively correlated with most of the cardio-metabolic risk factors; BMI, waist circumference, systolic and diastolic blood pressure, fasting blood glucose, triglyceride and total cholesterol. Serum resistin was found to be positively correlated with BMI, waist circumference, fasting blood glucose and total cholesterol. The difference in serum adiponectin and resistin level among MetS individuals indicated the potential of serum adiponectin and resistin to be used as a biomarker for the diagnosis of MetS among Temiar subtribe. [ABSTRACT FROM AUTHOR]

• Phytochemical characterization of ethanolic extract of the leaves from Mangifera indica. • Analyzes with extract of M. indica and its isolated majority compound (mangiferin). • Cytotoxic and anti-inflammatory evaluation of M. indica and mangiferin in vitro. • Post and co-treatment in vivo evaluated with M. indica and mangiferin. • Activity differences between extracts of M. indica and mangiferin. This study aimed phytochemical characterization (UPLC-DAD-MS/MS) of ethanolic extract of the leaves from Mangifera indica (EMI) and Mangiferin (MAN), analysis of the cytotoxic (MTT) and anti-inflammatory potential (expression of TNF-α) of EMI and MAN in vitro. In addition, was evaluate the effect on the mRNA expression of genes (CB1, PPARγ, adiponectin, resistin and leptin) associated with adipogenesis in adipose tissue of rats fed a cafeteria diet. Thus, wistar rats were treated by gavage with EMI and MAN for several days (according to the post and co-treatments). The adipose tissue was weighed and checked the expression of different markers by RT-PCR. The presence of MAN as major compound in EMI was verified. Both EMI and MAN were not cytotoxic, with lower EMI expression of TNF-α. Furthermore, EMI and MAN had proadipogenic action on post-treatment, while in the co-treatment, EMI attenuated the effect of adipogenesis and MAN increased the adipogenic process. [ABSTRACT FROM AUTHOR]

Type-II Endometrial Cancer (EMC) is one of the most common types of gynaecological cancer affecting more than 2.7 million people worldwide. Clinical evidence shows that adipokines levels are abnormally altered in Type-II EMC and reported to be one of the major responsible factor for uncontrolled proliferation and metastasis in Type-II EMC. Reversing the altered adipokine levels, therefore, help to control Type-II EMC proliferation and metastasis. In the present hypothesis we focus on the possible role of Thiazolidinediones in favourably altering the adipokine levels to benefit in the management of Type-II EMC. [ABSTRACT FROM AUTHOR]

Abstract Ethanolic extract of leaves of Morus alba L. (M. alba), known as white mulberry, was orally administered (100 mg/kg b.wt) for 8 weeks to female Wistar rats that were fed a high-cholesterol diet (HCD), to investigate the potential of M. alba leaves in attenuation of obesity, dyslipidemia, insulin resistance, and deficits in mood, cognitive as well as motor activity that are linked to the adipokines secretions of visceral adipose tissue. Results showed that M. alba diminished body weight gain, hypercholesterolemia, hypertriglyceridemia, atherogenic (AI) & coronary artery indices (CRI), and ameliorated glucose level and insulin resistance index in rats on HCD, compared with untreated HCD rats. Moreover, M. alba administration significantly decreased serum leptin and resistin contents as well as their mRNA expression in visceral adipose tissue, but significantly increased serum adiponectin level, and its mRNA expression in visceral adipose tissue in rats fed on HCD, compared to those in untreated HCD group. Regarding behavioral alterations, M. alba attenuated motor deficit, declined memory, depression and anxiety-like behavior, as well in rats on HCD, compared to that noticed in untreated HCD rats. The current data showed that serum leptin and resistin showed a positive correlation with and body weight gain, triglycerides (TG), AI as well as CRI, but showed a negative correlation with exploration, declined memory, depression- and anxiety-like behavior. Conversely, serum adiponectin showed a negative correlation with and body weight gain, TG, AI as well as CRI, but showed a positive correlation with locomotor activity, exploration, declined memory, and depression- and anxiety-like behavior. In conclusion, M. alba leaves supplementation could attenuate adiposity, insulin resistance behavioral deficits via down-regulation of regulation of gene expression of leptin, resistin, but up-regulation of adiponectin gene expression in the visceral adipose tissue of rats fed a high-cholesterol diet. Graphical abstract Unlabelled Image Highlights • Morus alba extract is rich in caffeic acid and quercetin derivatives. • Morus alba reduces obesity by targeting visceral adiposity and adipokines expression in obese rats. • Morus alba has anti-hyperglycemic and anti-hyperlipidemic effects. • Morus alba improves motor and cognitive behavior in obese rats. • Morus alba has anti-depressive and anxiolytic effects. [ABSTRACT FROM AUTHOR]

Abstract Continuously rising trends in obesity-related malignancies render this disease spectrum a public health priority. Worldwide, the burden of cancer attributable to obesity, expressed as population attributable fraction, is 11.9% in men and 13.1% in women. There is convincing evidence that excess body weight is associated with an increased risk for cancer of at least 13 anatomic sites, including endometrial, esophageal, renal and pancreatic adenocarcinomas; hepatocellular carcinoma; gastric cardia cancer; meningioma; multiple myeloma; colorectal, postmenopausal breast, ovarian, gallbladder and thyroid cancers. We first synopsize current epidemiologic evidence; the obesity paradox in cancer risk and mortality; the role of weight gain and weight loss in the modulation of cancer risk; reliable somatometric indicators for obesity and cancer research; and gender differences in obesity related cancers. We critically summarize emerging biological mechanisms linking obesity to cancer encompassing insulin resistance and abnormalities of the IGF-I system and signaling; sex hormones biosynthesis and pathway; subclinical chronic low-grade inflammation and oxidative stress; alterations in adipokine pathophysiology; factors deriving from ectopic fat deposition; microenvironment and cellular perturbations including vascular perturbations, epithelial-mesenchymal transition, endoplasmic reticulum stress and migrating adipose progenitor cells; disruption of circadian rhythms; dietary nutrients; factors with potential significance such as the altered intestinal microbiome; and mechanic factors in obesity and cancer. Future perspectives regarding prevention, diagnosis and therapeutics are discussed. The aim of this review is to investigate how the interplay of these main potential mechanisms and risk factors, exerts their effects on target tissues provoking them to acquire a cancerous phenotype. Highlights • Excess body weight is associated with an increased risk for a range of malignancies. • The triad of obesity, insulin resistance and adipokine aberrations is linked to cancer. • Subclinical chronic low-grade inflammation and oxidative stress is another mechanism. • Altered gut microbiome contributes to inflammation and release of carcinogenic products. • Microenvironmental perturbations and circadian rhythm disruption are additional mechanisms. [ABSTRACT FROM AUTHOR]

Summary Adipokines are biologically active cytokines that are mainly produced in adipose tissue. There is evidence, in man and mice, that some adipokines may be secreted in other tissues including the vascular endothelium, epithelia and sebaceous glands. Moreover, modified serum levels of adipokines have been detected in people with acne vulgaris or psoriasis; it is suspected that adipokines could contribute to local and systemic inflammatory conditions. We aimed to evaluate the expression of three adipokines (i.e. leptin, adiponectin and resistin) in normal canine skin. Formalin-fixed, paraffin wax-embedded punch biopsy samples were obtained from the sparsely-haired skin of the caudal ventral abdomen of a single clinically healthy dog with no history of skin disease. Immunohistochemistry was applied, using rabbit polyclonal primary antibodies specific for leptin, adiponectin and resistin. Adipokines were not expressed in normal canine dermis or hypodermis. In contrast, they were detected in the keratinocytes of all epidermal layers and hair follicle segments, sebocytes, apocrine gland cells and in the vascular endothelium. This is the first report on the expression of adipokines in normal canine skin, a first step in studying their role in the skin physiology and inflammatory skin diseases of dogs. [ABSTRACT FROM AUTHOR]

Abstract Objective Resistin is a hormone that has been associated with metabolic syndrome and cardiovascular disease. The role of resistin in patients with peripheral artery disease (PAD) has not been fully explored. This study seeks to understand the relationship between serum resistin, vascular function, and cardiovascular outcomes in patients with PAD. Methods There were 106 patients with PAD who were recruited between 2011 and 2016. Patients attended a baseline visit during which a comprehensive vascular physiology assessment including medical and surgical history, radial artery tonometry, and flow mediated-vasodilation (FMD) was completed. A blood sample was drawn, and serum resistin was assayed using enzyme-linked immunosorbent assay kits. Using the time of study enrollment as the time of origin, incident major adverse cardiac events (MACEs) were identified by subsequent chart review and defined as a composite end point of myocardial infarction, coronary revascularization, transient ischemic attack, stroke, or death from a cardiac cause. Results Patients had a mean age of 68 ± 8 years, were largely white (75%), and had comorbidities commonly associated with PAD including hypertension (92%), hyperlipidemia (87%), coronary artery disease (37%), and diabetes mellitus (38%). After stratification by resistin quartile, higher resistin quartiles were significantly associated with an older age, a greater number of pack-years smoked, and a lower estimated glomerular filtration rate. Despite similar comorbidities and medication use, endothelial function, as measured by FMD, was significantly lower with increasing resistin quartile (I, 9.1% ± 3.3%; II, 7.1% ± 3.5%; III, 5.8% ± 4.0%; IV, 5.6% ± 3.5%; P =.002). In multivariable linear regression, higher resistin quartiles (III and IV) were associated with lower FMD relative to quartile I after adjusting for several patient characteristics, medications, and comorbidities (III, −2.26 [95% confidence interval (CI), −4.51 to −0.01; P =.05]; IV, −2.53 [95% CI, −4.87 to −0.20; P =.03]). During a median follow-up period of 36 months (interquartile range, 29-45 months), 21 patients experienced the primary end point. In a Cox proportional hazards model adjusted for smoking status, coronary artery disease, and age, each 1 ng/mL increase in resistin was associated with a 10% increased risk of MACEs (hazard ratio, 1.10; 95% CI, 1.00-1.20; P =.04). Conclusions In patients with PAD, higher levels of resistin were associated with impaired endothelial function and an increased rate of MACEs. These results suggest that resistin may be a marker or effector of impaired vascular physiology and adverse cardiac outcomes in patients with PAD. Further research is needed to determine the potential mechanisms by which resistin may impair endothelial function and increase MACEs in this population. [ABSTRACT FROM AUTHOR]

Highlights • Resistin inhibits thrombin induced protein C activation. • Resistin reduces the expression of EPCR but not TM in HUVECs, mediated by SP1. • Blockage of SP1 abolished the effects of Resistin on protein C activation. Abstract Endothelial cells are vital to blood coagulation and maintain whole body hemostasis. Binding of endothelial cells to endothelial protein C receptor (EPCR) and thrombomodulin (TM) is essential to the formation of activated protein C (APC), one of the key factors regulating blood coagulation. In our study, we showed that resistin, an adipocyte hormone, suppresses thrombin-induced protein C activation in endothelial cells. Resistin treatment results in a reduction in EPCR expression, but not TM. Mechanistically, we demonstrate that resistin induces expression of the nuclear transcription factor SP-1, which could lead to downregulation of EPCR. Both inhibition and silencing of SP1 protein abolishes abnormal APC generation induced by resistin. Collectively, our data support a new role of resistin in disturbing APC formation. [ABSTRACT FROM AUTHOR]

Abstract Background Resistin is an immunometabolic mediator that is elevated in several inflammatory disorders. A ligand for Toll-like receptor 4, resistin modulates the recruitment and activation of myeloid cells, notably neutrophils. Neutrophils are major drivers of cystic fibrosis (CF) lung disease, in part due to the release of human neutrophil elastase- and myeloperoxidase-rich primary granules, leading to tissue damage. Here we assessed the relationship of resistin to CF lung disease. Methods Resistin levels were measured in plasma and sputum from three retrospective CF cohorts spanning a wide range of disease. We also assessed the ability of neutrophils to secrete resistin upon activation in vitro. Finally, we constructed a multivariate model assessing the relationship between resistin levels and lung function. Results Plasma resistin levels were only marginally higher in CF than in healthy control subjects. By contrast, sputum resistin levels were very high in CF, reaching 50–100 fold higher levels than in plasma. Among CF patients, higher plasma resistin levels were associated with allergic bronchopulmonary aspergillosis, and higher sputum resistin levels were associated with CF-related diabetes. Mechanistically, in vitro release of neutrophil primary granules was concomitant with resistin secretion. Overall, sputum resistin levels were negatively correlated with CF lung function, independently of other variables (age, sex, and genotype). Conclusions Our data establish relationships between resistin levels in the plasma and sputum of CF patients that correlate with disease status, and identify resistin as a novel mechanistic link between neutrophilic inflammation and lung disease in CF. [ABSTRACT FROM AUTHOR]

Highlights • The relationship between resistin levels with obesity and inflammatory markers in women without cardiovascular diseases was investigated. • Serum resistin levels were found to be increased in overweight and obese women. • It is suggested that resistin may be related to low-grade inflammation among obese subjects in the absence of overt cardiovascular diseases. Abstract Aims The convergence of obesity and inflammation in the pathogenesis of cardiovascular diseases (CVD) has been recognized over the past decade. Resistin has emerged as a novel secreted protein with links to both insulin resistance and inflammation. We aimed to investigate the relationship between changes in serum resistin levels with metabolic parameters, including obesity and inflammatory markers in women free of CVD. Methods and results A total of 200 apparently healthy women were consecutively recruited from the Out-patients Clinics at King Abdulaziz university Hospital in Jeddah, Saudi Arabia. They were classified into 4 groups based on quartile for serum resistin. Anthropometric variables were measured in all study subjects. Fasting blood samples were collected for measurement of lipid profile, blood glucose and inflammatory markers. Study subjects within the upper quartile (Q4) had significantly higher body height (p < 0.0001), waist and hip circumferences (p < 0.05) and inflammatory markers (p < 0.0001) values than those in the lower quartile (Q1). Significant correlations were found between circulating resistin levels and systolic blood pressure, some anthropometric measures as well as inflammatory markers. Conclusion Serum resistin levels were found to be increased in overweight and obese women. Resistin was also independently associated with hs-CRP in women free of CVD, suggesting that resistin may be related to low-grade inflammation among obese subjects in the absence of overt CVD. [ABSTRACT FROM AUTHOR]

Highlights • Considerable changes occur in adipokines' behaviour following critical illness. • Lower adiponectin at admission with gradual consequent increase might be a useful pattern in determining better outcomes. • Some clinical studies have suggested the adverse effects of elevated resistin and potential prognostic value of visfatin. • Experimental studies have proposed the therapeutic value of ghrelin in critical care. • High ADMA levels and low arginine: ADMA ratio were suggested as predictors of ICU mortality and morbidities. Abstract Adipose tissue products or adipokines play a major role in chronic endocrine and metabolic disorders; however, little is known about critical conditions. In this article, the experimental and clinical evidence of alterations of adipokines, adiponectin, leptin, resistin, visfatin, asymmetric dimethylarginine (ADMA), and ghrelin in critical illness, their potential metabolic, diagnostic, and prognostic value, and the gaps in the field have been reviewed. The results showed considerable changes in the concentration of the adipokines; while the impact of adipokines on metabolic disorders such as insulin resistance and inflammation has not been well documented in critically ill patients. There is no consensus about the circulatory and functional changes of leptin and adiponectin. However, it seems that lower concentrations of adiponectin at admission with gradual consequent increase might be a useful pattern in determining better outcomes of critical illness. Some evidence has suggested the adverse effects of elevated resistin concentration, potential prognostic importance of visfatin, and therapeutic value of ghrelin. High ADMA levels and low arginine:ADMA ratio were also proposed as predictors of ICU mortality and morbidities. However, there is no consensus on these findings. Although primary data indicated the role of adipokines in critical illness, further studies are required to clarify whether the reason of these changes is pathophysiological or compensatory. The relationship of pathophysiological background, disease severity, baseline nutritional status and nutrition support during hospitalization, and variations in body fat percentage and distribution with adipokines, as well as the potential prognostic or therapeutic role of these peptides should be further investigated in critically ill patients. [ABSTRACT FROM AUTHOR]

Abstract Background Neutrophil functions have been shown to be modulated by adipocytokines during atherogenesis. The immuno-regulatory role of resistin on neutrophil-mediated activities in atherosclerotic patients remains elusive. Here, we aimed at exploring the association between serum levels of resistin and neutrophil products either in the systemic circulation or within plaques in a cohort of patients with severe carotid plaque stenosis undergoing endarterectomy. In addition, we assessed the effects of resistin on neutrophil pro-atherosclerotic functions in vitro. Methods Inflammatory biomarkers, neutrophil products and resistin levels were assessed in patients' sera and carotid plaques by ELISA and immunohistochemistry analysis. In vitro, human primary neutrophils isolated from healthy donors were assessed on different substrate cultures for: degranulation (by ELISA), migration (by microchemotaxis Boyden chamber), F-actin polymerization (by fluorescent assay), integrin and chemokine receptor expression (by flow cytometry) and apoptosis (by both morphologic analysis and flow cytometry). Results Serum resistin was positively correlated with serum levels of neutrophil granule products, but inversely with intraplaque neutrophil and MMP-9 contents. In vitro, resistin was detected in supernatants of degranulating neutrophils and positively correlated with other granule products. Although resistin did not affect neutrophil degranulation, apoptosis and integrin or chemokine receptor expression, pre-incubation with human recombinant resistin abrogated CXCL8-induced neutrophil migration and F-actin polymerization by inhibiting ERK2 phosphorylation. Conclusion Resistin can be released by degranulating neutrophils and blunts neutrophil plaque infiltration by modulating their migration towards known atherosclerotic mediators. These results suggest a potential immunoregulatory role of resistin in inhibiting neutrophil-mediated atherosclerotic activities. Highlights • Resistin is positively correlated with neutrophil granule products in serum. • Resistin is inversely correlated with intraplaque neutrophil and MMP-9 contents. • Resistin does not affect neutrophil degranulation and apoptosis. • Resistin abrogates CXCL8-induced neutrophil migration in vitro. [ABSTRACT FROM AUTHOR]

Highlights • This study is the first to determine resistin levels in patients with CPP. • CPP patients have lower concentrations of resistin than prepubertal and pubertal girls with overweight or obesity without CPP. • Resistin levels were not found to be related to z-BMI, body fat percentage or CPP treatment status. Abstract Objective To compare serum resistin concentrations between prepubertal girls with a BMI > 85th percentile and girls with precocious puberty (CPP) who have and have not undergone GnRH analog treatment. Patients and methods This is a cross-sectional study in girls with a BMI > 85th percentile and a median age of 8 years. We included 31 girls with CPP who did not receive treatment (CPPoT), 23 girls with CPP who were treated with leuprolide (CPPT), 22 prepubertal girls and 24 pubertal girls. Anthropometric data and the fasting plasma concentrations of lipids, glucose, insulin, and resistin were measured. Results The z-BMI scores were similar among the groups (p = 0.344), and body fat percentage (BF%) was similar among CPPT, CPPoT and prepubertal girls (p = 0.151). Resistin and insulin levels were lower in girls with CPP (CPPT and CPPoT) than in prepubertal and pubertal girls (median resistin level: CPPT 11.8 pg/ml vs CPPoT 11 pg/ml vs prepubertal 16 pg/ml vs pubertal 16 pg/ml, p = 0.001; median insulin level: CPPT 10.7 μUI/mL vs CPPoT 10.2 μUI/mL vs prepubertal 14.4 μUI/mL vs pubertal 32 μUI/mL p = 0.02). ANCOVA analysis, after adjustments for pubertal stage, BF% and z-BMI, showed that CPP modifies resistin levels (F = 31.4; p = 0.0001) independently of these parameters (p < 0.05). Conclusions In the group of girls with overweight or obesity, the resistin level was lower in girls with CPP than in prepubertal and pubertal girls. More studies are needed to understand the role of resistin in CPP patients. [ABSTRACT FROM AUTHOR]

Highlights • Intermuscular adipose tissue may contribute to the chronic inflammation associated with obesity and increased risk of cardiometabolic disease. • Intermuscular adipose tissue may contribute to the chronic inflammation associated with increased risk of cardiometabolic disease. Abstract Objective This study examined the associations between abdominal IMAT area and density with inflammatory markers associated with cardiometabolic disease. Methods 1897 participants enrolled in the Multi-Ethnic Study of Atherosclerosis underwent computed tomography to quantify body composition and measurements of adiponectin, leptin, interleukin-6 (IL-6), C-reactive protein (CRP), and resistin. Results The mean age and body mass index of participants was 65 years and 28 kg/m2, respectively, and 50% were female. After adjustment for age, sex, and race/ethnicity, as IMAT area increased and density decreased from the first to fourth quartile, markers of inflammation increased linearly (p < 0.01). Using linear regression, and with adjustment for demographics, cardiovascular disease risk factors, and abdominal muscle area and density, a 1-standard deviation (SD) increase in total abdominal IMAT area was associated with a 21%, 36% and 20% higher IL-6, leptin, and CRP, respectively, and 19% lower adiponectin (p < 0.001). With similar adjustment, a 1-SD decrease in total abdominal IMAT density was associated with a 14%, 32%, and 15% higher IL-6, leptin, and CRP, respectively, and 22% lower adiponectin (p < 0.001). These associations were attenuated with the addition of visceral fat (p > 0.05). Conclusions Abdominal IMAT area and density are associated with inflammatory markers, with these associations attenuated by central adiposity. [ABSTRACT FROM AUTHOR]

Background: Our recent research showed that resistin has a neuroprotective effect against stroke-induced injury through suppressing apoptosis and oxidative stress. However, the molecular mechanism of neuroprotection of resistin is unclear. This work was designed to examine the effect of mouse recombinant resistin on mRNA expression of Tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β), Interleukin-10 (IL-10), Transforming growth factor-β1 (TGF- β1), and Heat shock protein-70 (HSP-70) in mouse model of stroke.Materials and Methods: Transient focal cerebral ischemia was induced by the middle cerebral artery occlusion (MCAO) in mice. TNF-α, IL-1β, IL-10, TGF-β1, and HSP-70 mRNA were detected at sham (0 hour), 3 hours, 6 hours, 12 hours, and 24 hours after MCAO using real-time QRT-PCR method. Moreover, animals were treated with resistin at the dose of 400ng/mouse at the commencement of MCAO, and mRNA expression of the cytokines and HSP-70 was measured 24 hours after MCAO.Results: Tumor necrosis factor-α and IL-1β mRNA expression markedly increased at 12-hour time point and then returned to the basal level at 24 hours after MCAO; but HSP-70 mRNA expression increased at 24-hour time point. Furthermore, resistin (400 ng/mouse) significantly increased TGF-β1 and IL-10 and decreased HSP-70 gene expression at 24 hours after MCAO.Conclusions: Our findings revealed that a molecular mechanism of attenuating ischemic damage by resistin administration probably is increased mRNA expression of anti-inflammatory cytokines. However, applying resistin in the clinical settings for the treatment of stroke deserves further researches in the future. [ABSTRACT FROM AUTHOR]

Abstract Work in cattle and rodents has shown that resistin, in addition to its roles in insulin resistance and inflammation, is involved in the regulation of gonadal steroidogenesis. However, the role of resistin in the regulation of reproductive processes in other species, such as seasonally breeding sheep, is completely unknown. Herein, we tested the hypothesis that resistin can influence the secretion of anterior pituitary hormones and that its effect in ewes is dependent on the day length. Thirty Polish Longwool ewes, a breed that exhibits a strong seasonal reproductive pattern, were ovariectomized with estrogen replacement using subcutaneously inserted estradiol implants. Ewes were fed ad libitum and housed under a natural photoperiod (longitude: 19°57′ E, latitude: 50° 04′ N). Intravenous treatments consisted of control or recombinant bovine resistin (rbresistin) in saline: (1) control (saline; n = 10), (2) low resistin dose (1.0 μg/kg BW; n = 10), and (3) high resistin dose (10.0 μg/kg BW; n = 10). Experiments were conducted during both short-day (SD) and long-day (LD) seasons using 5 sheep per group within each season. Blood samples were collected every 10 min over 4 h. Blood plasma concentrations of FSH, LH, and prolactin (PRL) were assayed using RIA. A season × dose interaction was observed for all hormonal variables measured. Greater concentrations (P < 0.001) of LH and FSH were observed during SDs than during LDs in all groups. During SDs, the high dose (10 μg/kg BW) decreased (P < 0.001) basal LH levels and amplitude (P < 0.05) of LH pulses and increased (P < 0.001) circulating concentrations of FSH. However, the low dose of resistin decreased (P < 0.001) FSH concentrations compared to those of controls. During LDs, both the low and high resistin doses increased mean concentrations of LH (P < 0.001 and P < 0.05, respectively) and FSH (P < 0.001). A high dose of rbresistin increased (P < 0.001) the mean circulating concentrations of PRL during both seasons. However, in all groups, concentrations of PRL were greater during LDs than SDs. These results demonstrate for the first time that resistin is involved in the regulation of pituitary hormone secretion and that this effect is differentially mediated during LDs and SDs. Highlights • Depending on the dose and the length of the day, resistin modulates LH basal secretion (P < 0.001) and pulse pattern (P < 0.05) in seasonally breeding sheep. • During LDs, both the low and high resistin doses increased mean concentrations of FSH (P < 0.001). • A high dose of resistin increased (P < 0.001) the mean circulating concentrations of PRL during both seasons. • Resistin is engaged in modulation of reproductive hormone secretion on the level of pituitary in seasonally breeding sheep. [ABSTRACT FROM AUTHOR]

High-fat diet consumption causes hypothalamic inflammation, dysregulating the leptin pathway, which, in turn, compromises the modulation of hypothalamic neuronal activities and predisposes obesity development. Intermittent fasting (IF) and exercise training (ET) have been demonstrated as efficient interventions to modulate hypothalamic inflammation and neuronal activity. However, no studies have evaluated whether combining these interventions could induce better results in reestablishing hypothalamic homeostasis disrupted by high-fat diet intake. The 8-week-old male C57BL/6 mice were randomly assigned into 2 groups: sedentary mice fed a standard diet (CT), and sedentary mice fed a high-fat diet (HF). After 8 weeks of an HF diet, part of the HF group (now 16 weeks old) was randomly subjected to different interventions for 6 weeks: HF-IF = HF diet mice submitted to IF; HF-T = HF diet mice submitted to ET; HF-IFT = HF diet mice submitted to IF and ET. All interventions decreased the body weight gain induced by high-fat diet intake, associated with reduced calorie consumption in week 14. Only the HF-IFT group presented improved serum insulin, leptin, resistin, and Tnf-alpha levels concomitantly with decreased hypothalamic inflammation. The HF-IFT group also demonstrated increased Pomc mRNA expression associated with enhanced pSTAT3 expression in the hypothalamic arcuate and ventromedial hypothalamic nuclei. Our data indicate that the beneficial effects of the combination of IF and ET on energy homeostasis are associated with increased leptin sensitivity in the hypothalamic arcuate nucleus and ventromedial hypothalamic nucleus, which is likely due to an improvement in hypothalamic inflammatory pathways in these nuclei. [ABSTRACT FROM AUTHOR]