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White adipose tissue (WAT) is not only an energy storage reservoir that is critical in energy homeostasis but is also a highly metabolically active endocrine organ. WAT can secrete a variety of adipocytokines, including leptin (LEP), adiponectin (APN), resistin, visfatin, tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6), and osteopontin (OPN). It can also synthesize and secrete exosomes, which enhance intercellular communication and participate in various physiological processes in the body. It can also synthesize and secrete exosomes to enhance intercellular communication and participate in a variety of physiological processes in the body. The skeleton is an important organ for protecting internal organs. It forms the scaffolding of the body and gives the body its basic form. It drives muscle contraction to produce movement under the regulation of the nervous system. It is also an important hematopoietic organ; and it is regulated by the cytokines secreted by WAT. As research related to the release of adipocytokines from WAT to affect the skeleton continues to progress, an inextricable link between bone lipid regulation has been identified. In this paper, we review the literature to summarize the structure, function and metabolism of WAT, elaborate the specific molecular mechanisms by which WAT‐secreted hormones, cytokines and exosomes regulate skeletal cells, provide a theoretical basis for the in‐depth study of WAT cross‐organ regulation of bone, and provide new ideas for finding new adipose‐secreted targeting factors for the treatment of skeletal diseases. [ABSTRACT FROM AUTHOR]

Purpose: Derangements of liver transcriptional factors and enzymes have important implications in diabetes-induced related complications. Hence, this study which consists of two experimental phases was aimed at evaluating the possible underlying molecular mechanisms of intermittent fasting (IF), exercise starvation and honey in streptozotocin (STZ)-mediated liver damage in diabetic rats. Methods: The diabetic rats were treated orally with distilled water (0.5 ml/kg), IF, starvation and honey at 1 g/kg body weight in the non-diabetic phase for four (4) weeks. After STZ injections, four (4) weeks of IF, exercise, starvation, and honey therapy were used as interventions prior to a biochemical evaluation of the liver. Results: IF and exercise greatly decreased liver transcription factor (resistin, SREBP-1c), inflammatory cytokines/enzyme (TNF-α, IL-6, IL-1ß, MPO) as well as oxidative and nitrergic stress with correspondence increased liver PPAR-γ, IL-10, SOD, CAT and GSH in diabetic rats unlike starvation and honey regimen relative to diabetic controls. Furthermore, IF and exercise significantly improved hepatic glycogen synthase and decreased glycogen phosphorylase in diabetic rats compared to the diabetic control group, but starvation and honey therapy had no such influence. IF and exercise strategically reduces STZ-induced liver metabolic disorder via through modulation of liver transcriptional factors and inhibition of pro-inflammatory cytokines, oxido-nitrergic and adipokine signaling pathway. [ABSTRACT FROM AUTHOR]

Resistin, an adipocyte-specific hormone involved in insulin resistance and adipocyte differentiation, was initially identified in adipose tissue and macrophages. The physiological role of this molecule in camels remains largely unexplored. This study analysed for the first time blood and tissue levels of resistin as well as expression of resistin gene by real time PCR in adipose tissue (hump, visceral & epididymal) and different muscles (gastrocnemius, heart and caecum) in dromedary camels. The results revealed that resistin concentration was significantly (P<0.01) higher in epididymal adipose tissue as compared to other tissues and the lowest concentration was detected in serum. Additionally, the differential mRNA expression levels of resistin gene showed the highest expression level in epididymal adipose tissue as compared to other tissues. In conclusion, the results demonstrated for the first time that resistin was expressed in different tissues of dromedary camels. These data underscore an important facet of the physiological role of resistin as a factor involved in insulin resistance and glucose metabolism in camels. [ABSTRACT FROM AUTHOR]

Crocetin (CCT) is a natural saffron-derived apocarotenoid that possesses healthy properties such as anti-adipogenic, anti-inflammatory, and antioxidant activities. Lipolysis is enhanced in obesity and correlates with a pro-inflammatory, pro-oxidant state. In this context, we aimed to investigate whether CCT affects lipolysis. To evaluate CCT's possible lipolytic effect, 3T3-L1 adipocytes were treated with CCT10μM at day 5 post-differentiation. Glycerol content and antioxidant activity were assessed using colorimetric assays. Gene expression was measured using qRT-PCR to evaluate the effect of CCT on key lipolytic enzymes and on nitric oxide synthase (NOS) expression. Total lipid accumulation was assessed using Oil Red O staining. CCT10μM decreased glycerol release from 3T3-L1 adipocytes and downregulated adipose tissue triglyceride lipase (ATGL) and perilipin-1, but not hormone-sensitive lipase (HSL), suggesting an anti-lipolytic effect. CCT increased catalase (CAT) and superoxide dismutase (SOD) activity, thus showing an antioxidant effect. In addition, CCT exhibited an anti-inflammatory profile, i.e., diminished inducible NOS (NOS2) and resistin expression, while enhanced the expression of adiponectin. CCT10μM also decreased intracellular fat and C/EBPα expression (a transcription factor involved in adipogenesis), thus revealing an anti-adipogenic effect. These findings point to CCT as a promising biocompound for improving lipid mobilisation in obesity. [ABSTRACT FROM AUTHOR]

Obesity is an emerging concern globally with increasing prevalence. Obesity is associated with many diseases, such as cardiovascular disease, dyslipidemia, and cancer. Thus, effective new antiobesity drugs should be urgently developed. We synthesized SW20.1, a compound that induces activating transcription factor 3 (ATF3) expression. The results of Oil Red O staining and quantitative real-time polymerase chain reaction revealed that SW20.1 was more effective in reducing lipid accumulation in 3T3-L1 preadipocytes than the previously synthesized ST32db, and that it inhibited the expression of the genes involved in adipogenesis and lipogenesis. A chromatin immunoprecipitation assay indicated that SW20.1 inhibited adipogenesis and lipogenesis by binding to the upstream promoter region of resistin at two sites (−2861/−2854 and −241/−234). In mice, the intraperitoneal administration of SW20.1 reduced body weight, white adipocyte weight in different regions, serum cholesterol levels, adipogenesis-related gene expression, hepatic steatosis, and serum resistin levels. Overall, SW20.1 exerts antiobesity effects by inhibiting resistin through the ATF3 pathway. Our study results indicate that SW20.1 is a promising therapeutic drug for diet-induced obesity. [ABSTRACT FROM AUTHOR]

Obesity is fast growing as a global pandemic and is associated with numerous comorbidities like cardiovascular disease, hypertension, diabetes, gastroesophageal reflux disease, sleep disorders, nephropathy, neuropathy, as well as asthma. Studies stated that obese asthmatic subjects suffer from an increased risk of asthma, and encounter severe symptoms due to a number of pathophysiology. It is very vital to understand the copious relationship between obesity and asthma, however, a clear and pinpoint pathogenesis underlying the association between obesity and asthma is scarce. There is a plethora of obesity-asthma etiologies reported viz., increased circulating pro-inflammatory adipokines like leptin, resistin, and decreased antiinflammatory adipokines like adiponectin, depletion of ROS controller Nrf2/HO- 1 axis, nucleotide-binding domain, leucine-rich-containing family, pyrin domaincontaining-3 (NLRP3) associated macrophage polarization, hypertrophy of WAT, activation of Notch signaling pathway, and dysregulated melanocortin pathway reported, however, there is a very limited number of reports that interrelates these pathophysiologies. Due to the underlying complex pathophysiologies exaggerated by obese conditions, obese asthmatics respond poorly to anti-asthmatic drugs. The poor response towards anti-asthmatic drugs may be due to the anti-asthmatics approach only that ignores the anti-obesity target. So, aiming only at the conventional antiasthmatic targets in obese-asthmatics may prove to be futile until and unless treatment is directed towards ameliorating obesity pathogenesis for a holistic approach towards amelioration of obesity-associated asthma. Herbal medicines for obesity as well as obesity-associated comorbidities are fast becoming safer and more effective alternatives to conventional drugs due to their multitargeted approach with fewer adverse effects. Although, herbal medicines are widely used for obesity-associated comorbidities, however, a limited number of herbal medicines have been scientifically validated and reported against obesity-associated asthma. Notable among them are quercetin, curcumin, geraniol, resveratrol, ß-Caryophyllene, celastrol, tomatidine to name a few. In view of this, there is a dire need for a comprehensive review that may summarize the role of bioactive phytoconstituents from different sources like plants, marine as well as essential oils in terms of their therapeutic mechanisms. So, this review aims to critically discuss the therapeutic role of herbal medicine in the form of bioactive phytoconstituents against obesity-associated asthma available in the scientific literature to date. [ABSTRACT FROM AUTHOR]

Background: To investigate the association between clinical periodontal parameters of periodontitis, serum lipid metabolism markers and adipokines' levels in patients with obesity and periodontitis. Methods: A total of 112 patients admitted to Hospital of Xi'an Jiaotong University were included in this study. They were divided into normal body weight group (18.5 < body mass index, BMI < 25, n = 36), overweight group (25 ≤ BMI < 30, n = 38), and obesity group (BMI ≥ 30, n = 38) accordingly. The diagnosis of periodontitis was based on the newest international classification of periodontitis. Full-mouth clinical periodontal measurements included: plaque index, periodontal pocket depth, clinical attachment level, and bleeding on probing. Gingival crevicular fluid samples were analyzed for: Interleukin-1β, tumor necrosis factor-α, Interleukin-6 and C-reactive protein. Serum triglycerides, total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol and glycosylated hemoglobin levels were measured. Visfatin, leptin, resistin, and adiponectin levels in serum were also measured. Results: The ratio of participants without periodontitis was significantly highest in normal weight group, and the proportion of severe periodontitis (stage III and IV) was highest in obesity group. The periodontal pocket depth, clinical attachment level, and the inflammatory cytokines in gingival crevicular fluid in obesity group and overweight group were higher than those in normal body weight group. The BMI and waist-to-hip ratio (WHR) were significantly positive correlated with periodontal pocket depth and clinical attachment level. Using a Multivariate logistic regression model, periodontitis correlates to BMI, WHR, serum levels of triglyceride, total cholesterol, low density lipoprotein, and adipokines such as visfatin, leptin, and resistin. Conclusions: Obesity is positively correlated with the aggravation of periodontitis. Obesity may aggravate the damage to periodontal tissue by regulating the secretion level of adipokines. [ABSTRACT FROM AUTHOR]

Context: Circulating adipokines and ghrelin affect bone remodeling by regulating the activation and differentiation of osteoblasts and osteoclasts. Although the correlation between adipokines, ghrelin, and bone mineral density (BMD) has been studied over the decades, its correlations are still controversial. Accordingly, an updated meta-analysis with new findings is needed. Objective: This study aimed to explore the impact of serum adipokine and ghrelin levels on BMD and osteoporotic fractures through a meta-analysis. Data sources: Studies published till October 2020 in Medline, Embase, and the Cochrane Library were reviewed. Study selection: We included studies that measured at least one serum adipokine level and BMD or fracture risk in healthy individuals. We excluded studies with one or more of the following: patients less than 18 years old, patients with comorbidities, who had undergone metabolic treatment, obese patients, patients with high physical activities, and a study that did not distinguish sex or menopausal status. Data extraction: We extracted the data that include the correlation coefficient between adipokines (leptin, adiponectin, and resistin) and ghrelin and BMD, fracture risk by osteoporotic status from eligible studies. Data synthesis: A meta-analysis of the pooled correlations between adipokines and BMD was performed, demonstrating that the correlation between leptin and BMD was prominent in postmenopausal women. In most cases, adiponectin levels were inversely correlated with BMD. A meta-analysis was conducted by pooling the mean differences in adipokine levels according to the osteoporotic status. In postmenopausal women, significantly lower leptin (SMD = -0.88) and higher adiponectin (SMD = 0.94) levels were seen in the osteoporosis group than in the control group. By predicting fracture risk, higher leptin levels were associated with lower fracture risk (HR = 0.68), whereas higher adiponectin levels were associated with an increased fracture risk in men (HR = 1.94) and incident vertebral fracture in postmenopausal women (HR = 1.18). Conclusions: Serum adipokines levels can utilize to predict osteoporotic status and fracture risk of patients. [ABSTRACT FROM AUTHOR]

Background: Asthma is a chronic inflammatory disorder of the airways with diverse overlapping pathologies and phenotypes contributing to a significant heterogeneity in clinical manifestations. Obesity may modify asthma risk, phenotype, and prognosis. A suggested mechanism linking obesity and asthma is through systemic inflammation. Adipokines secreted by adipose tissue were suggested to provide a link between obesity and asthma. Objective: To have an understanding for the contribution of adiponectin, resistin and MCP-1 to development of distinct asthma phenotype in overweight/obese children through assessment of their serum level and correlation to pulmonary function tests. Subjects and methods: The study included 29 normal weight asthmatics, 23 overweight/obese asthmatic children and 30 controls. All cases were subjected to detailed history taking, thorough examination and pulmonary function tests. Serum adiponectin, resistin, MCP-1 and IgE were assessed to all recruited subjects. Results: Adiponectin level was significantly higher in overweight/obese asthmatics (24900 ± 1600 ng/ml) compared to normal weight asthmatics (21700 ± 1700 ng/ml) and control (23000 ± 3200 ng/ml), (p < 0.001 & 0.051 respectively). Normal weight asthmatics had significantly lower adiponectin level than control, (p = 0.039). A significant low level of MCP-1 in overweight/obese asthmatics (149.5 (20—545) ng/L) compared to control (175 (28 -1123.5) ng/L), p = 0.037. No significant difference was found regarding resistin. Normal weight asthmatics had significantly lower FEV1% and FVC% compared to overweight/obese asthmatics (p = 0.036, 0.016 respectively). A significant positive correlation was found between (FEV1%, FVC) and BMI in normal weight asthmatics (P = 0.01, < 0.01 respectively) and a significant negative correlation between PEF and BMI (-0.42, p = 0.05) in obese/overweight asthmatics. Resistin/adiponectin ratio was not affected by sex, degree of asthma severity or level of asthma control in either normal weight or overweight/obese asthmatic. Conclusion: This work could suggest that adiponectin may play a role in overweight/obese asthma phenotype where it is possible to have a dual action (pro & anti- inflammatory). It seems that resistin had no role in asthma pathogenesis. [ABSTRACT FROM AUTHOR]

Introduction: Risk factors for type 2 diabetes mellitus (T2DM) include obesity and some genetic factors. Obesity involves mild chronic inflammation that predisposes cells to insulin resistance. Two genes that influence obesity and insulin resistance are Proconvertase-1 (PC-1) and resistin (RETN). PC-1 affects the activation of hormones that regulate satiety and hunger. Resistin is one of the inflammatory factors that influence the occurrence of insulin resistance. This study aimed to determine the influence of polymorphism in the PC-1 gene rs1044498 (C>A) and resistin gene RETN + 299 G>A rs3745367 on the risk of diabetes in obese Papua population. Methods: This study involved 58 obese people with T2DM and 58 obese people without DM. We examined the characteristics of blood pressure, lipid profile and insulin resistance by HOMA-IR. The genes examined were PC-1 rs1044498 (C>A) and RETN+ 299 G>A rs3745367 by the PCR-RFLP method. The relationship of gene variations with biochemical parameters was determined with analysis of variance. The results were considered significantly different if P < 0.05. Results: In this study, parameters of diastolic blood pressure, triglycerides and insulin resistance were higher while high density lipoprotein (HDL) levels were lower and significantly different in the obese with T2DM group compared to the obese only group. The carrier of the A allele in the PC-1 gene rs1044498 was higher in the obese group than the obese with T2DM but not significantly different in biochemical parameters. Carrier of the AA genotype in the RETN gene + 299 G>A rs3745367 had higher triglycerides and HOMA-IR and lower HDL levels significantly different (P<0.05) than other genotypes in the obesity with T2DM group. Conclusion: PC-1 rs1044498 gene was a risk factor for obesity but not for T2DM, while RETN gene rs3745367 was a risk factor for dyslipidemia and diabetes in obese people in the Papua population. [ABSTRACT FROM AUTHOR]

Aim/Introduction: Resistin, which induces insulin resistance, is mainly expressed in monocytes/macrophages in humans. We reported previously that serum resistin was highest in the G–A haplotype defined by resistin single nucleotide polymorphisms (SNPs) at −420 (rs1862513) and − 358 (rs3219175). As sarcopenic obesity is associated with insulin resistance, we aimed to examine whether serum resistin and its haplotypes were associated with sarcopenic obesity at a latent stage. Materials and Methods: We cross‐sectionally analyzed 567 community‐dwelling Japanese participants attending annual medical check‐ups in which the sarcopenic obesity index was evaluated. The age‐ and gender‐matched normal glucose tolerance subjects with G–A homozygotes and those with C–G homozygotes were examined via RNA‐sequencing and pathway analysis (each n = 3), and RT‐PCR (each n = 8). Results: In multivariate logistic regression analyses, the fourth quartile (Q4) of serum resistin and G–A homozygotes were both associated with the latent sarcopenic obesity index defined by a visceral fat area of ≥ 100 cm2 and grip strength Q1 after adjustment for age and gender, with or without other confounding factors. RNA sequencing and pathway analysis showed that tumor necrosis factor (TNF) was involved in the top five pathways in the whole blood cells of G–A homozygotes compared with C–G homozygotes. RT‐PCR revealed that TNF mRNA was higher in G–A homozygotes than in C–G homozygotes. Conclusions: The G–A haplotype was associated with the latent sarcopenic obesity index defined by grip strength in the Japanese cohort, could be mediated by TNF‐α. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is one of the most common neurodegenerative diseases affecting elderly people. Considering the gap in the literature on melatonin and adipokine levels in PD patients at various stages of the disease, we conducted a study to investigate the levels of selected parameters in PD patients at the disease's early (ES) and advanced (AS) stages. Melatonin, leptin, adiponectin, and resistin concentrations were measured in the blood serum of 20 PD patients without dyskinesia (ES), 24 PD patients with dyskinesia (AS), and 20 healthy volunteers as a control group (CG). The data were analyzed using ANOVA. Melatonin was significantly lower in ES (p < 0.05) and higher in AS patients (p < 0.05) compared to CG. The level of leptin was increased both in ES (p < 0.001) and AS (p < 0.001) versus CG, while resistin was increased only in patients with dyskinesia (p < 0.05). Higher melatonin (p < 0.001) and resistin (p < 0.05) and lower leptin (p < 0.05) levels were found in AS versus ES. The main findings of the study include the changes in inflammatory markers' levels during PD and a surprising increase in melatonin level in dyskinesia patients. Further research is necessary, which will be aimed at modulating the secretion of melatonin and adipokines as a treatment target for PD. [ABSTRACT FROM AUTHOR]

Due to their multidirectional influence, adipocytokines are currently the subject of numerous intensive studies. Significant impact applies to many processes, both physiological and pathological. Moreover, the role of adipocytokines in carcinogenesis seems particularly interesting and not fully understood. For this reason, ongoing research focuses on the role of these compounds in the network of interactions in the tumor microenvironment. Particular attention should be drawn to cancers that remain challenging for modern gynecological oncology—ovarian and endometrial cancer. This paper presents the role of selected adipocytokines, including leptin, adiponectin, visfatin, resistin, apelin, chemerin, omentin and vaspin in cancer, with a particular focus on ovarian and endometrial cancer, and their potential clinical relevance. [ABSTRACT FROM AUTHOR]

Background: Adipocytokines are signaling molecules secreted by adipose tissue contributing to the control of body fat, energy expenditure and secretion of insulin and cytokines. They have been related to the development of obesity, type-2 diabetes, cardiovascular diseases and cancer. Diet and physical activity (PA) may have beneficial effects on their level. We evaluated the effects of a 24-month dietary and/or PA intervention on plasma levels of adipocytokines as a secondary analysis in the DAMA (Diet, physical Activity and Mammography) trial. Methods: The 234 study participants (healthy postmenopausal women with high breast density, 50–69 years, non-smokers, no hormone therapy) were randomised to four arms: (1) isocaloric dietary intervention mainly based on plant-foods; (2) moderate-intensity PA intervention with at least 1 h/week of supervised strenuous activity; (3) both interventions; (4) general recommendations on healthy dietary and PA patterns. Leptin, resistin and adiponectin were measured at baseline and at the end of the intervention. Analyses were performed using Tobit regression. Results: After 24 months, women randomised to PA intervention (arms #2 + #3) showed significant lower level of leptin (37.5% lower) and resistin (65.6% lower) compared to the control group (arms #1 + #4). No significant differences emerged in adiponectin levels. No significant differences in leptin, resistin and adiponectin levels at follow-up emerged in women randomised to the dietary intervention (arms #1 + #3) in comparison with controls (arms #2 + #4). Conclusion: This study supports the effectiveness of PA, even at moderate intensity, in improving the leptin and resistin profile in postmenopausal women. Trial registration number: ISRCTN28492718, date of trial registration 17/05/2012. [ABSTRACT FROM AUTHOR]

Background: An imbalance of adipokines, hormones secreted by white adipose tissue, is suggested to play a role in the immunopathology of multiple sclerosis (MS). In people with MS (PwMS) of the same age, we aimed to determine whether the adipokines adiponectin, leptin, and resistin are associated with MS disease severity. Furthermore, we aimed to investigate whether these adipokines mediate the association between body mass index (BMI) and MS disease severity. Methods: Adiponectin, resistin, and leptin were determined in serum using ELISA. 288 PwMS and 125 healthy controls (HC) were included from the Project Y cohort, a population-based cross-sectional study of people with MS born in the Netherlands in 1966, and age and sex-matched HC. Adipokine levels and BMI were related to demographic, clinical and disability measures, and MRI-based brain volumes. Results: Adiponectin levels were 1.2 fold higher in PwMS vs. HC, especially in secondary progressive MS. Furthermore, we found a sex-specific increase in adiponectin levels in primary progressive (PP) male patients compared to male controls. Leptin and resistin levels did not differ between PwMS and HC, however, leptin levels were associated with higher disability (EDSS) and resistin strongly related to brain volumes in progressive patients, especially in several grey matter regions in PPMS. Importantly, correction for BMI did not significantly change the results. Conclusion: In PwMS of the same age, we found associations between adipokines (adiponectin, leptin, and resistin) and a range of clinical and radiological metrics. These associations were independent of BMI, indicating distinct mechanisms. [ABSTRACT FROM AUTHOR]

Background: Proinflammatory and immunomodulatory adipokines are linked to inflammation in critically ill patients but are poorly studied after injury. We hypothesized that trauma would induce systemic adipokine release and influence erythroid suppression. Methods: Blood and bone marrow (BM) were collected from trauma patients (ISS > 15, n = 90) and compared to patients undergoing elective hip replacement (n = 37). Plasma adipokine levels were measured, and BM was assayed for adipokine transcription and erythroid progenitor growth potential. Differences were detected using t-tests and correlations using simple linear regression. Results: Trauma patients exhibited decreased adiponectin (1.8* vs 3.4 mg/mL) and increased leptin (7.8* vs 4.6 ng/mL) and resistin (3.1* vs 2.5 ng/mL), with sex- and age-specific differences. They also showed increased BM visfatin transcription. Adipokine transcription negatively correlated with erythroid progenitor growth. Conclusion: Adipose tissue activity is linked to inflammatory responses after injury, with variability by age and sex. Bone marrow adipose tissue may influence erythroid recovery after trauma. [ABSTRACT FROM AUTHOR]

Summary: Obesity is recognized as a risk factor for adverse outcome in COVID‐19, but the molecular mechanisms underlying this relationship remain unknown. Adipose tissue functions as an endocrine organ by secreting multiple pro‐inflammatory and anti‐inflammatory factors, known as adipocytokines, which could be involved in COVID‐19 severity. We explored the role of adipocytokines in COVID‐19 and its association with BMI, clinical outcome, and inflammation. This is an observational study in 195 hospitalized COVID‐19 patients. Serial plasma concentrations of the adipocytokines leptin, adiponectin, resistin, and various inflammatory cytokines were assessed. Adipocytokines were compared between patients with normal weight (BMI: 18.5–24.9 kg/m2), overweight (BMI: 25.0–29.9 kg/m2), and obesity (BMI ≥ 30 kg/m2), between patients admitted to the ICU and to non‐ICU clinical wards, and between survivors and non‐survivors. Patients with overweight and obesity displayed higher leptin concentrations and lower adiponectin concentrations throughout hospital admission (p <.001), whereas resistin concentrations were not different from patients with normal weight (p =.12). Resistin concentrations correlated with inflammatory markers and were persistently higher in ICU patients and non‐survivors compared to non‐ICU patients and survivors, respectively (both p <.001), whereas no such relationships were found for the other adipocytokines. In conclusion, leptin and adiponectin are associated with BMI, but not with clinical outcomes and inflammation in COVID‐19 patients. In contrast, resistin is not associated with BMI, but high concentrations are associated with worse clinical outcomes and more pronounced inflammation. Therefore, it is unlikely that BMI‐related adipocytokines or differences in the inflammatory response underlie obesity as a risk factor for severe COVID‐19. [ABSTRACT FROM AUTHOR]

Background: The purpose of the current study was evaluation of the utility of seminal plasma (SP) resistin and leptin in predicting successful surgical sperm retrieval (SSR) in men with non-obstructive azoospermia (NOA). Methods: This prospective comparative study was conducted in the andrology clinic of a specialized fertility center. In total, 53 NOA men as candidates for either first time micro‐testicular sperm extraction (micro-TESE) or repeat micro-TESE and 28 normozoospermic controls were included. ELISA was used for measurement of SP resistin and leptin levels in all participants. Significance level was defined as p< 0.05. Results: The current study demonstrated a significant positive correlation between estradiol (E2) level in serum and SP resistin (r=0.342, p=0.025). Also, there was a highly significant positive correlation between SP leptin and SP resistin (r=0.568, p= 0.001). Interestingly, SP leptin was the only variable that demonstrated a significant correlation with eventful micro-TESE outcome in men who underwent micro-TESE for the first time. Finally, ROC curve showed that SP leptin level of 4.05 ng/ml predicted successful SSR in men who underwent micro-TESE for the first time with a sensitivity of 73.3% and a specificity of 75% as 11 out of 27 (41%) cases showed eventful micro-TESE at or above this cut-off level [AUC of 0.747, 95% CI, lower bound of 0.555, and upper bound of 0.939, p=0.030]. Conclusion: SP leptin can be used as a non-invasive biomarker to predict successful SSR in NOA cases undergoing first time micro-TESE, while SP resistin failed to play the same role. [ABSTRACT FROM AUTHOR]

This study attempts to assess the concentration of two opposite-acting adipokines (anti-inflammatory adiponectin and pro-inflammatory resistin) in antidepressant-resistant patients undergoing ketamine infusion (KI) and electroconvulsive therapy (ECT). The study group comprised 52 patients hospitalised due to episodes of depression in the course of bipolar disorders. The Hamilton depression scale was used to assess the intensity of the depression symptoms before starting therapy and one day after its completion. The serum concentration of adipokines was determined before and after the therapeutic intervention using an ELISA method. Baseline adipokine levels differed between patients receiving KI and ECT therapy. Regardless of the procedure used, these levels changed after treatment, with the nature of these changes being different. In the case of KI, the adiponectin levels increased, and resistin levels decreased. In contrast, after ECT, the concentrations of both adipokines decreased. Changes in adipokine concentrations correlated with improvement in mental status, as assessed by the Hamilton Rating Scale, type of bipolar disorder, and gender. Adipokines remain interesting candidate biomarkers in assessing the state and course of the disease depending on the therapeutic procedure applied. However, the relatively small study group and limited original research available for discussion justify further investigation. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic and immune-mediated skin condition characterized by pro-inflammatory cytokines and keratinocyte hyperproliferation. Dendritic cells, T lymphocytes, and keratinocytes represent the main cell subtypes involved in the pathogenesis of psoriasis, while the interleukin-23 (IL-23)/IL-17 pathway enhances the disease progression. Human adipose tissue is an endocrine organ, which secretes multiple proteins, known as adipokines, such as adiponectin, leptin, visfatin, or resistin. Current evidence highlights the immunomodulatory roles of adipokines, which may contribute to the progression or suppression of psoriasis. A better understanding of the complexity of psoriasis pathophysiology linked with adipokines could result in developing novel diagnostic or therapeutic strategies. This review aims to present the pathogenesis of psoriasis and the roles of adipokines in this process. [ABSTRACT FROM AUTHOR]

Background: Resistin is a molecule that belongs to the Resistin-Like Molecules family (RELMs), the group of proteins taking part in inflammatory processes. Increased resistin concentrations are observed in cardiovascular complications. Resistin contributes to the onset of atherosclerosis and intensifies the atherosclerotic processes. The aim of this study was to investigate the relationship between resistin and cardiovascular (CV) risk in men with chronic kidney disease (CKD) not treated with dialysis. Materials and Methods: One hundred and forty-two men were included in the study: 99 men with eGFR lower than 60 mL/min/1.73 m2 and 43 men with eGFR ≥ 60 mL/min/1.73 m2. CV risk was assessed. Serum resistin, tumor necrosis factor-alpha (TNF-alpha) and plasminogen activator inhibitor-1 (PAI-1) were measured among other biochemical parameters. Results: We observed that resistin concentrations were significantly higher in patients with CKD compared to individuals with eGFR ≥ 60 mL/min/1.73 m2 (p = 0.003). In CKD, after estimating the general linear model (GLM), we found that resistin is associated with CV risk (p = 0.026) and PAI-1 serum concentrations (0.012). The relationship of PAI-1 with resistin depends on the level of CV risk in CKD (p = 0.048). Conclusions: Resistin concentrations rise with the increase of CV risk in CKD patients and thus resistin may contribute to the progression of cardiovascular risk in this group of patients. The relationship between resistin and CV risk is modified by PAI-1 concentrations. [ABSTRACT FROM AUTHOR]

BackgroundAdipokines have inflammatory and fibrotic properties that may be critical in interstitial lung disease (ILD). We examined associations of serum adipokine levels with CT imaging-based measures of subclinical ILD and lung function among community-dwelling adults.MethodsA subset of the original Multi-Ethnic Study of Atherosclerosis cohort (n = 1,968) had adiponectin, leptin, and resistin measured during follow-up visits (2002-2005). We used regression models to examine associations of adiponectin, leptin, and resistin levels with (1) high-attenuation areas (HAAs) from CT scans (2004-2005, n = 1,144), (2) interstitial lung abnormalities (ILAs) from CT scans (2010-2012, n = 872), and (3) FVC from spirometry (2004-2006, n = 1,446). We used -(1/HAA2), which we denoted with H, to model HAA as our outcome to meet model assumptions.ResultsHigher adiponectin was associated with lower HAA on CT imaging among adults with a BMI ≥ 25 kg/m2 (P for BMI interaction = .07). Leptin was more strongly associated with ILA among never smokers compared with ever smokers (P for smoking interaction = .004). For every 1-SD increment of log-transformed leptin, the percent predicted FVC was 3.8% lower (95% CI, -5.0 to -2.5). Higher serum resistin levels were associated with greater HAA on CT in a fully adjusted model. For every 1-SD increment of log-transformed resistin there was an increase in H of 14.8 (95% CI, 3.4-26.3).ConclusionsHigher adiponectin levels were associated with lower HAA on CT imaging among adults with a higher BMI. Higher leptin and resistin levels were associated with lower FVC and greater HAA, respectively.

Abstract Some studies proposed the anti‐inflammatory effect of soy protein and soy isoflavones by changing the serum adiponectin and resistin levels. The purpose of this research was to determine the impact of soy isoflavones and soy protein on blood adiponectin and resistin levels in adults. Scopus, PubMed, Cochrane Library, ISI Web of Science, and ClinicalTrials.gov databases were searched until April 2022. The effect size was computed by the mean changes from the beginning for intervention and comparison groups and their standard deviation. In the case of significant heterogeneity, DerSimonian and Laird random‐effects model was used. Six and five clinical trials were selected for the systematic review and meta‐analysis, respectively. The overall estimate indicated that soy isoflavones in combination with soy protein did not significantly change serum adiponectin level (weighted mean differences (WMD) = 0.36 μg/ml; 95% confidence interval (CI): −0.26, 0.99; p = .25), but significantly increased serum resistin level (WMD = 0.64 ng/ml, 95% CI: 0.25, 1.04; p = .001). In combination with soy protein, soy isoflavones nonsignificantly increased serum adiponectin levels, but significantly increased resistin levels. New intervention studies with a high dose of soy isoflavones and soy protein in different parts of the world and an updated meta‐analysis are needed to confirm the results of our study.

Background Plasminogen activator inhibitor 1 (PAI-1) and resistin are associated with dysfunctional adipose tissue (AT)-related metabolic complications. The role of dietary eicosapentaenoic (EPA) and docosahexaenoic (DHA) fatty acids in this relationship is unknown. Aim To investigate the association of EPA and DHA with PAI-1 and resistin, as well as the role of this association on the glucose metabolism of apparently healthy subjects. Subjects and methods Thirty-six healthy individuals were included. Validated food frequency questionnaires were used to analyse dietary habits. Inflammatory and glucose metabolism markers were quantified. Subcutaneous AT samples were obtained, and adipocyte number, area, and macrophage content were assessed. Results In 36 subjects aged 56 ± 8 years and with a body mass index of 26 ± 4 kg/m2, logEPA, and logDHA showed significant association with logresistin and a marginal association with PAI-1. Adipocyte number, area, and lognumber of macrophages per adipocyte significantly correlated with PAI-1 but not with logresistin. Although logEPA and logDHA were independently associated with loginsulin, loginsulin resistance, and C-Peptide, the addition of logresistin, but not of PAI-1, into the multivariable model, abolished the associations. Conclusions EPA and DHA could modulate glucose metabolism across AT functional states. Our data indicate that this association is independent of other metabolic risk factors.

Early screening of complications of diabetes mellitus (DM) is one of the priorities for public health. Most patients with type 1 diabetes mellitus (T1DM) are patients of working age. New strategies for the primary prevention of cardiovascular disease (CVD) are needed to prevent their early disability. Aim. To assess the predictive value of adipokines in relation to a personalized approach to the need for an in-depth examination of young patients with T1DM. Materials and methods. The study included 98 patients without CVD: 70 patients with T1DM (mean age 26.48.1 years) and 28 patients without DM (mean age 279 years). All patients underwent a general clinical examination, the levels of adipokines were determined, ergospirometry, echocardiography, and bioimpedancemetry were performed. Results. Changes in the cardiorespiratory system in patients with T1DM were revealed, in comparison with persons without T1DM: anaerobic threshold was reached faster (p=0.001), maximum oxygen consumption was lower (p=0.048), metabolic equivalent was reduced (p=0.0001). Signs of myocardial remodeling were found in the T1DM group: there was an increase in the relative wall thickness (p=0.001), the posterior wall of the left ventricle (p=0.001), myocardial mass index (p=0.049), in comparison with persons without T1DM. Changes in the adipokines system were revealed: higher levels of resistin (p=0.002) and visfatin (p=0.001), lower level of adiponectin (p=0.040) in T1DM. A positive correlation was found between posterior wall of the left ventricle and visfatin (p=0.014) and a negative relationship between adiponectin and relative wall thickness (p=0.018) in T1DM. Conclusion. In T1DM, even at a young age, there are multifactorial changes in the heart, which can be detected even at the preclinical stage. The data obtained can be used to identify groups of patients at high risk of developing dangerous CVD in T1DM, which can form the basis for determining the timing of the start of preventive therapy.

Abstract Background Periodontitis is a major inflammatory disease of the oral mucosa that is not limited to the oral cavity but also has systemic consequences. Although the importance of chronic periodontitis has been emphasized, the systemic immune response induced by periodontitis and its therapeutic effects remain elusive. Here, we report the transcriptomes of peripheral blood mononuclear cells (PBMCs) from patients with periodontitis. Methods Using single-cell RNA sequencing, we profiled PBMCs from healthy controls and paired pre- and post-treatment patients with periodontitis. We extracted differentially expressed genes and biological pathways for each cell type and calculated activity scores reflecting cellular characteristics. Intercellular crosstalk was classified into therapy-responsive and -nonresponsive pathways. Results We analyzed pan-cellular differentially expressed genes caused by periodontitis and found that most cell types showed a significant increase in CRIP1, which was further supported by the increased levels of plasma CRIP1 observed in patients with periodontitis. In addition, activated cell type-specific ligand-receptor interactions, including the BTLA, IFN-γ, and RESISTIN pathways, were prominent in patients with periodontitis. Both the BTLA and IFN-γ pathways returned to similar levels in healthy controls after periodontal therapy, whereas the RESISTIN pathway was still activated even after therapy. Conclusion These data collectively provide insights into the transcriptome changes and molecular interactions that are responsive to periodontal treatment. We identified periodontitis-specific systemic inflammatory indicators and suggest unresolved signals of non-surgical therapy as future therapeutic targets.

Abstract Aims Resistin is a circulating inflammatory biomarker that is associated with cardiovascular disease. We investigated the associations of resistin and incident heart failure (HF) and its subtypes, as well as specific measures of subclinical HF (myocardial fibrosis and relevant biomarkers). Methods We analysed data from 1968 participants in the Multi‐Ethnic Study of Atherosclerosis with measurements of plasma resistin levels at clinic visits from 2002 to 2005. Participants were subsequently followed for a median of 10.5 years for HF events. The associations between resistin levels and incident HF, HF with reduced ejection fraction (HFrEF), and HF with preserved ejection fraction (HFpEF) were examined using multivariable Cox proportional hazards models. Linear regression models assessed the associations between resistin levels and myocardial fibrosis from cardiac magnetic resonance imaging, as well as hs‐cTnT and NT‐proBNP. Results The mean age of the cohort was 64.7 years, and 50.0% were female. Seventy‐four participants (4%) developed incident HF during follow‐up. In a Cox proportional hazards model adjusted for age, gender, education level, race/ethnicity, and traditional risk factors, higher resistin levels were significantly associated with incident HF (HR 1.44, CI 1.18–1.75, P = 0.001) and HFrEF (HR 1.47, CI 1.07–2.02, P = 0.016), but not with HFpEF (HR 1.25, CI 0.89–1.75, P = 0.195). Resistin levels showed no significant associations with myocardial fibrosis, NT‐proBNP, or hs‐cTnT levels. Conclusions In a multi‐ethnic cohort free of cardiovascular disease at baseline, elevated resistin levels were associated with incident HF, more prominently with incident HFrEF than HFpEF, but not with subclinical myocardial fibrosis or biomarkers of HF.

Latar belakang. Sepsis merupakan penyebab utama morbiditas dan mortalitas pada layanan kesehatan anak di seluruh dunia. Resistin merupakan salah satu hormon peptida yang berpotensi sebagai penanda dalam sepsis didasari dari aktivitas resistin dalam sekresi mediator inflamasi. Tujuan. Penelitian ini bertujuan menilai korelasi kadar resistin dengan CRP dan PCT pada anak yang terdiagnosis sepsis. Metode. Penelitian cross-sectional dilakukan pada pasien anak berusia usia >1 bulan – 18 tahun yang dirawat di RSHS periode September – Desember 2021. Data yang diambil berupa karakteristik dasar, kadar resistin, CRP, dan PCT. Analisis statistik dilakukan dengan menggunakan uji korelasi Rank Spearman dan analisis multivariat regresi linier. Hasil. Sebanyak 60 pasien yang terdiri atas 31 (51,7%) perempuan dan 29 (48,3%) laki-laki. Sebagian besar usia berada pada rentang 1-6 tahun (53,3%), dengan median usia sebesar 5,5 tahun dengan IQR sebesar 8,9 tahun. Status gizi pada riset ini sebagian besar normal sebanyak 25 anak (41,7%) dan malnutrisi berat sebanyak 15 (25,0%). Hasil analisis bivariat terdapat korelasi positif lemah antara resistin dengan CRP (r=0,225; p=0,042), tidak terdapat korelasi resitin dengan PCT (r=0,114; p=0,193), serta terdapat korelasi positif sedang antara CRP dengan PCT (r=0,442; p

Background/Objectives: 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). Methods: 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. Results: Irisin inversely correlated with BMI (p

Objective:Cystic echinococcosis (CE) is one of the most common zoonotic diseases worldwide. Diagnosis of CE is predominantly based on imaging techniques and serological tests are used in cases of non-characteristic imaging findings as diagnostic reference. However, serological test results cannot be completely reliable as they are affected by multi-factors. P-selectin and resistin are inflammatory markers that are altered during the acute stages of infection. In this purpose, inflammatory markers as P-selectin and resistin have been investigated for a potential diagnostic reference for CE diagnosis.Methods:A total of 60 patients who were diagnosed with CE and twenty-five healthy individuals were included in this study. Blood samples were obtained from all participants. Obtained sera were evaluated using the P-selectin and resistin ELISA kits for protein levels. Additionally, the relative expression of SELP (P-selectin) and RETN (resistin) genes were determined using the comparative CT (ΔΔCT) method between groups as CE patients with active and inactive cysts, CE patients and healthy controls.Results:SELP (13.9-fold change, p0.05). There was no difference between active and inactive CE patients in terms of P-selectin and resistin in gene and protein levels (p>0.05).Conclusion:Although there was no difference between the active and inactive CE patients, the good differentiation between the healthy controls and the CE patients suggested that resistin is a potential inflammatory diagnostic reference.

Abstract Background Previous studies have been reported that vitamin D deficiency increased the risk of metabolic syndrome (MetS). Nonetheless, the exact mechanisms underlying this association is unclear. Besides, inflammation and deregulation of adipokines secretion have been recognized as pivotal factors that contribute to the pathogenesis of these conditions. Therefore, we assessed whether serum vitamin D status is associated with serum levels of adipokines and inflammatory markers in these patients. Methods This case-control study was carried out among 65 patients with MetS who had vitamin D insufficiency (cases) and 130 MetS patients who had vitamin D sufficiency (controls). Cases and controls were recruited from among those referred to health centers in Zabol County, Iran. Vitamin D insufficiency was regarded as a serum 25-hydroxyvitamin D [25(OH)D] concentration below 30 ng/ml. Serum concentrations of leptin, adiponectin, visfatin, and resistin and also adiponectin/leptin ratio along with serum levels of interleukin 6 (IL-6), IL-10 and tumor necrosis factor-alpha (TNF-α), were evaluated. Results Serum levels of leptin, resistin, and TNF-α were significantly higher, whereas, serum adiponectin and adiponectin/leptin ratio were significantly lower in cases than the controls. There was no significant difference in serum visfatin, IL-6, and IL-10 between the groups. Serum levels of 25(OH)D were inversely correlated with leptin, resistin, and TNF-α in both unadjusted models and after adjustment for potential confounders. Conclusion Our findings indicated that vitamin D insufficiency in MetS patients is associated with increased inflammation and serum adipokine abnormalities which may be associated with developing metabolic complications in these patients.

Objectives: to evaluate the effectiveness of multidose supplementation of vitamin D on the dynamics of serum levels of markers of lipid metabolism in pregnant women with obesity. Materials and methods. The study included 75 pregnant women with the І degree of obesity and low vitamin D status, who were divided into subgroups depending on the vitamin D dose of and the baseline 25(OH)D level in blood serum: I subgroup – 24 women with 25(OH)D less than 22.0 ng/ml who received Decristol 4000 IU/day; II subgroup – 26 pregnant women with 25(OH)D = 22.1–28.0 ng/ml who received Decristol 2000 IU/day; III subgroup – 25 patients with 25(OH)D over 28.1 ng/ml, who received 1000 IU of vitamin D per day. Pregnant women of all these subgroups also took acetylsalicylic acid at a dose of 100 mg/day. The control group included 26 practically healthy women who received 600 IU of vitamin D per day. Serum adipokinins levels were studied at 11–13, 22–24 and 31–33 weeks of gestation. Results. Significant differences were found in the increase of leptin (p < 0.0001) and resistin (p < 0.0001) and the decrease of adiponectin (p = 0.006) in pregnant women with impaired vitamin D metabolism against the background of moderate obesity in the І trimester compared to the control group. A more positive effect was found for Decristol 4000 IU (patients with vitamin D deficiency), against the treatment of Decristol 2000 IU (patients with vitamin D deficiency). At 31–33 weeks of gestation, there was a statistically significant decrease in serum level of resistin (p = 0.006) and a similar increase in adiponectin (p = 0.025) in patients receiving vitamin D 4000 IU, compared with the same indicators in clinical subgroups. Resistin and adiponectin may be markers of perinatal pathology in obese pregnant women in the first trimester of gestation, in terms of specificity (91.5 and 78.7%, respectively), sensitivity (100.0 and 91.3%, respectively); positive probability (11.75 and 4.29%, respectively), negative prognostic value (100.0 and 94.9%, respectively) and test accuracy (94.3 and 82.9%, respectively). Conclusions. The use of markers of lipid metabolism as diagnostic criteria during pregnancy in women with the І degree of obesity and low vitamin D status has predictor and prognostic value for the risk of perinatal pathology and helps to assess the effectiveness of comprehensive prophylactic therapy.

Jeffrey Bonenfant,1,2,&ast; Jiang Li,3,&ast; Luqman Nasouf,1 Joseph Miller,3 Tammy Lowe,1 Lukasz Jaroszewski,3 Xinru Qiu,3 Suman Thapamagar,1,2 Aarti Mittal,1,2 Adam Godzik,3 Walter Klein,1,2,&ast; Meera G Nair3,&ast; 1Department of Medicine, Division of Pulmonary and Critical Care Medicine, Riverside University Health System Medical Center, Moreno Valley, CA, USA; 2Division of Pulmonary, Critical Care, Hyperbaric, Allergy and Sleep Medicine, School of Medicine, Loma Linda University, Loma Linda, CA, USA; 3Division of Biomedical Sciences, School of Medicine, University of California Riverside, Riverside, CA, USA&ast;These authors contributed equally to this workCorrespondence: Meera G Nair, Division of Biomedical Sciences, School of Medicine, University of California Riverside, 3135 Multidisciplinary Research Building 1, 900 University Avenue, Riverside, CA, CA92521, USA, Tel +951-827-7734, Email meera.nair@medsch.ucr.eduBackground: Sepsis mortality has remained unchanged for greater than a decade, and early recognition continues to be the most important factor in mortality outcome. Plasma resistin concentration is increased in sepsis, but its mechanism and clinical relevance is unclear. As one function, resistin interacts with toll-like receptor 4 in competition with lipopolysaccharide, a main component of the gram-negative bacterial cell wall. It is not known if the type of infection leading to sepsis influences resistin production. The objective of this study was to investigate whether 1) early plasma resistin concentration can predict mortality, 2) elevated plasma resistin concentration is associated with clinical disease severity scores, such as SOFA, mSOFA and APACHE II, and 3) plasma resistin concentrations differ between gram negative versus other etiologies of sepsis.Methods: This was an exploratory study in the framework of a prospective observational design. Peripheral venous blood samples were obtained from subjects admitted to the intensive care unit at clinical recognition of sepsis (0 hour) and at 6 and 24 hours. Vasopressor utilization was not a requirement for inclusion. Plasma was analyzed for resistin concentration by ELISA. Cytokine concentrations including IL-6, IL-8, and IL-10 were determined by cytokine bead array. Cytokine data were evaluated against publicly available sepsis RNA expression datasets to compare protein versus RNA expression levels in predicting clinical disease state. Clinical data were collected from electronic health records for clinical severity index calculations and context for interpretation of resistin and cytokine concentrations. Subjects were followed up to 60 days, or until death, whichever came first. Statistical analysis was completed with R package and SPSS software.Results: Resistin levels were elevated in subjects admitted to the intensive care unit with sepsis. Four-hundred subjects were screened with 45 subjects included in the final analysis. Thirteen of 45 patients were non-survivors. Mortality within 60 days correlated with significantly higher resistin concentrations than in survivors. A resistin concentration of > 126 ng/mL at clinical recognition of sepsis and > 197 ng/mL within the first 24 hours were associated with mortality within 60 days with an area under the curve of 0.82 and 0.88, respectively. Most subjects with resistin concentration greater than these threshold values were deceased prior to 30 days. Resistin concentrations correlated with SOFA, mSOFA, and APACHE II scores in addition to having association with increases in inflammatory and sepsis biomarkers. These associations were validated with analysis of RNA expression datasets.Conclusion: Plasma resistin concentrations of > 126 ng/mL at clinical recognition of sepsis and > 197 ng/mL within the first 24 hours of clinical sepsis recognition are associated with all-cause mortality. Resistin concentration within this timeframe also has comparable mortality association to well-validated clinical severity indices of SOFA, mSOFA, and APACHE II scores.Keywords: resistin, gram-negative, sepsis, mortality

Jianing Li, Shuo Li, Ling Yu, Jin Wei, Shuang Li, Hongyu Tan Department of Anesthesiology, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of ChinaCorrespondence: Hongyu Tan, Department of Anesthesiology, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China, Tel +86-10-88196107, Email maggitan@yeah.netPurpose: As an adipocyte-secreted hormone, resistin is linked to inflammation, insulin resistance and atherosclerosis. Currently, resistin is proposed as a novel biomarker for postoperative pain intensity. However, due to the various types of surgery and limited numbers of studies, previous conclusions should be validated. This study aimed to explore the effect of resistin polymorphism (rs3745367) on pain thresholds and sufentanil consumption in gastric cancer patients.Patients and Methods: A total of 148 gastric cancer patients enrolled in this study had their pain thresholds measured before surgery. After the exclusion of 16 patients, the characteristics of demography and clinic, numerical rating scale (NRS) and sufentanil consumption of 132 patients were recorded. Rs3745367 of resistin was identified by Sanger sequencing. Multivariate linear regression analysis was performed for sufentanil consumption and mechanical pain threshold.Results: The distributions of the GG, AG, and AA genotypes of rs3745367 among the participants were 54 (40.9%), 65 (49.2%), and 13 (9.9%), respectively. The mechanical pain threshold (P=0.04) and postoperative sufentanil consumption in the 1st 24 h (P=0.03) were significantly different among GG, AG, and AA genotype carriers. There was no significant difference among the three genotypes for the heat pain threshold and cold pain threshold. Regarding the NRS, no statistically significant difference among the three different genotypes was found 24 h postoperatively.Conclusion: Rs3745367 of resistin is associated with the mechanical pain threshold and postoperative sufentanil consumption in gastric cancer patients. Patients with the AA genotype of rs3745367 present an increased mechanical pain threshold and decreased postoperative sufentanil consumption.Keywords: gene polymorphism, pain threshold, postoperative pain, resistin, sufentanil consumption

Background: We have explored dementia's blood-based protein biomarkers in the Texas Alzheimer's Research and Care Consortium (TARCC) study. Among them are adipokines, i.e., proteins secreted by adipose tissue some of which have been associated with cognitive impairment. Objective: To associate adipokines with dementia severity and replicate their association across cohorts and biofluids (serum /plasma). Methods: We used eight rationally chosen blood-based protein biomarkers as indicators of a latent variable, i.e., "Adipokines". We then associated that construct with dementia severity as measured by the latent dementia-specific phenotype "δ" in structural equation models (SEM). Significant factor loadings and Adipokines' association with δ were replicated across biofluids in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Results: Eight adipokine proteins loaded significantly on the Adipokines construct. Adipokines measured in plasma (ADNI) or serum (TARCC) explained 24 and 70% of δ's variance, respectively. An Adipokine composite score, derived from the latent variables, rose significantly across clinical diagnoses and achieved high areas under the receiver operating characteristic curve (ROC/AUC) for discrimination of Alzheimer's disease from normal controls (NC) or cases of mild cognitive impairment (MCI) and between NC and MCI. Conclusion: These results again suggest that SEM can be used to create latent biomarker classifiers that replicate across samples and biofluids, and that a substantial fraction of dementia's variance is attributable to peripheral blood-based protein levels via the patterns codified in those latent constructs. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer is currently one of the most common types of cancer and the number one cause of cancer-related deaths in women worldwide. Despite significant advances involving cancer research in cancer biology, targeted treatments, and novel surgical approaches, breast cancer poses a constant, prominent challenge. In order to combat this reality, novel biomarkers and treatment targets are constantly on the rise. One of the known risk factors and survival predictors of breast cancer is obesity and obesity-related hormonal changes. The main effectors of said hormonal changes are a group of fatty tissue-related molecules, adipokines. Adipokines have many known and intertwined mechanisms of actions, many of which are known to enable carcinogenesis within the breast tissue. This review aims to summarize all available evidence of relationships between adipokines and the development of breast cancer, in order to emphasize their potential roles as novel biomarkers, predictive indicators, and possible future therapeutic targets of breast cancer. With the recent leaps in medicine, the landscape of our knowledge regarding adipose tissue has changed dramatically: it is now widely regarded as a fully functional endocrine organ. In addition, evidence from observational studies has linked the pathogenesis of diseases like breast cancer with adipose tissue and mainly with the adipokines that are secreted in its microenvironment, with the catalog continuously expanding. Examples include leptin, visfatin, resistin, osteopontin, and more. This review aims to encapsulate the current clinical evidence concerning major adipokines and their link with breast cancer oncogenesis. Overall, there have been numerous meta-analyses that contribute to the current clinical evidence, however more targeted larger-scale clinical studies are still expected to solidify their clinical utility in BC prognosis and reliability as follow-up markers. [ABSTRACT FROM AUTHOR]

Hidradenitis suppurativa (HS) is a chronic, recurrent, debilitating disorder of the pilosebaceous unit. Although its pathophysiology is not fully explained, inflammation seems to play an essential role in the development of HS. A link between obesity – often considered a state of chronic inflammation – and a higher prevalence of HS has been described. Nevertheless, the exact association is not well understood. Adipose tissue is a highly active endocrine organ that produces and secretes a variety of metabolically and immunologically active molecules called adipokines. The imbalances in concentrations of several adipokines in patients with HS have already been described. A shift towards the overproduction of proinflammatory adipokines (including leptin, resistin and visfatin) with the suppression of anti-inflammatory ones (adiponectin) has been noted. We conducted a review of the available data on adipokines in HS, concentrating on the described imbalances in adipokine concentrations, as well as possible implications in HS pathogenesis. Moreover, new, unstudied adipokines with possible implications in the development of HS are proposed. [ABSTRACT FROM AUTHOR]

Background: despite the relationship of resistin with metabolic syndrome (MS), the relationship of the 5'UTR intron C/T variant single nucleotide ploymorphism (SNP) rs7139228 of the RETN gene with the presence of MS has not been evaluated. Objective: the objective of this study is to evaluate the influence of SNP rs7139228 of the RETN gene on circulating resistin levels, as well as on MS in obese subjects. Material and methods: a Caucasian population of 1003 obese subjects was enrolled. An anthropometric evaluation (weight, waist circumference, fat mass), evaluation of nutritional intake, biochemical study (glucose, insulin, C-reactive protein, lipid profile, insulin, HOMA-IR, resistin) and rs7139228 genotype was carried out. Results: genotype distribution was: 852 subjects with GG (84.9 %), 147 subjects with GA (14.7 %) and 4 subjects with AA (0.4 %). The allelic frequency was G (0.92) and A (0.08). Serum levels of resistin (delta: 1.7 ± 0.2 ng/ml; p = 0.01), insulin (delta: 4.2 ± 0.4 IU/L; p = 0.01) and HOMA-IR (delta: 1.9 ± 0.2 units; p = 0.03) were higher in patients carrying the A allele than in non-carriers. The overall prevalence of MS was 48.1 %. A logistic regression analysis showed a high percentage of hyperglycemia (OR = 1.60, 95 % CI = 1.08-2.96; p = 0.02) and metabolic syndrome (OR = 1.33, 95 % CI = 1.07-3.39, p = 0.02) in carriers of the A allele after adjusting for resistin levels, sex, BMI and age. Conclusions: the A allele of the genetic variant rs7139228 is associated with higher levels of resistin, basal insulin, insulin resistance, and prevalence of metabolic syndrome in obese subjects. [ABSTRACT FROM AUTHOR]

Malnutrition is classified as one of the Giant Geriatric Syndromes. It carries serious consequences, such as sarcopenia or depression, which lead to functional disability. The main objective of this study was to identify parameters of oxidative stress and adipokines, which may be potential biomarkers of malnutrition in hospitalized older patients. During the study, selected parameters were determined in 137 senile patients, taking into account their nutritional status determined according to the Mini Nutritional Assessment (MNA), as well as an additional tool, namely the Geriatric Nutritional Risk Index (GNRI). Leptin and resistin were determined as the parameters with statistically significant differences between the patients classified according to the MNA. This phenomenon was confirmed using the GNRI classification. However, additional parameters for which differences were observed include the oxidized low-density lipoprotein level and activity of glutathione peroxidase. In conclusion, the determination of the mentioned markers in hospitalized senile patients as an adjunct to the routine assessment of nutritional status might be suggested to identify the early risk of malnutrition so that a personalized nutritional therapy can be implemented as early as possible. [ABSTRACT FROM AUTHOR]

Objective To observe the degree of hypertrophy and the expression of ferroptosis-related proteins in H9C2 resistin-induced rat cardiomyocytes pre-cultured with ferroptosis inhibitor ferrostatin-1 (Fer-1). Methods H9c2 cells were starved for 16 h and randomly divided into four groups. H9c2 cells in the group 1 were cultured in the medium containing 1 µmmol/L Fer-1 for 16 h, and then in the medium containing 50 ng/mL resistin for 32 h. H9c2 cells in the group 2 were cultured in Fer-1 medium containing 1 µmmol/L for 16 h and then in 0. 1% FBS medium for 32 h. H9c2 cells in the group 3 were cultured in medium containing 50 ng/mL resistin for 48 h. H9c2 cells in the group 4 (normal control group) were cultured with 0. 1% FBS for 48 h. After cells in each group were cultured, and the cell surface area was measured by ImageJ software, the single cell protein content was measured by BCA method, and the cardiomyocyte hypertrophy-related genes ANP, BNP and β-MHC were detected by RT-qPCR； ferroptosis-related proteins glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long-chain family member 4 (ACSL4) and cyclooxygenase 2 (Cox2) were detected by Western blotting. Results Compared with the group 4, the surface area of H9c2 cells in the group 3 increased significantly, the content of single-cell protein increased significantly, the expression levels of embryonic genes ANF, BNF, and β-MHC in the group 3 were significantly up-regulated, the expression of GPX4 protein was significantly down-regulated, and the protein expression levels of ACSL4 and COX2 were significantly up-regulated (all P<0. 05). Compared with the group 3, the surface area of H9c2 cells in the group 1 decreased significantly, the content of single-cell proteins decreased significantly, and the expression levels of embryonic genes ANF, BNF, and β-MHC in the group 1 were significantly reduced, the expression of GPX4 protein was significantly up-regulated, and the expression levels of ACSL4 and COX2 proteins were significantly down-regulated (all P<0. 05). Conclusions Fer-1 could inhibit H9C2 cell hypertrophy induced by resistin. Fer-1 may inhibit resistin-induced H9c2 hypertrophy by promoting the expression of ferroptosis-related protein GPX4 and inhibiting the expression of ACSL4 and COX2 proteins. [ABSTRACT FROM AUTHOR]

Obesity is a chronic, progressive and relapsing disease that produces many adverse health, social and economic effects. The aim of the study was to analyse the concentrations of selected proinflammatory parameters in the saliva of obese and normal body weight individuals. The study included 116 people divided into two groups: the study group (n = 75, subjects with obesity) and the control group (n = 41, individuals with normal body weight). Bioelectrical impedance analysis was performed, and saliva samples were collected from all study participants to determine the concentrations of selected proinflammatory adipokines and cytokines. Statistically significantly higher concentrations of MMP-2, MMP-9 and IL-1β were found in the saliva of obese women compared to women with normal body weight. Furthermore, statistically significantly higher concentrations of MMP-9, IL-6 and resistin were observed in the saliva of obese men compared to men with normal body weight. Higher concentrations of selected proinflammatory cytokines and adipokines were found in the saliva of obese individuals compared to individuals with normal body weight. It is likely that higher concentrations of MMP-2, MMP-9 and IL-1β can be detected in the saliva of obese women compared to non-obese women, while higher concentrations of MMP-9, IL-6 and resistin can be found in the saliva of obese men compared to non-obese men, which suggests that further research to confirm our observations and determine the mechanisms of development of metabolic complications associated with obesity depending on gender is needed. [ABSTRACT FROM AUTHOR]

Head and neck cancers (HNCs) are a group of tumors not common in European populations. So far, not much is known about the role of obesity, adipokines, glucose metabolism, and inflammation in the pathogenesis of HNC. The aim of the study was to determine the concentrations of ghrelin, omentin-1, adipsin, adiponectin, leptin, resistin, visfatin, glucagon, insulin, C-peptide, glucagon-like peptide-1 (GLP-1), plasminogen activator inhibitor-1 (PAI-1), and gastric inhibitory peptide (GIP) in the blood serum of HNC patients depending on their body mass index (BMI). The study included 46 patients divided into two groups according to their BMI values: the normal BMI group (nBMI) included 23 patients with BMI < 25 kg/m2 and the increased BMI group (iBMI) included patients with BMI ≥ 25 kg/m2. A control group (CG) included 23 healthy people (BMI < 25 kg/m2). Statistically significant differences in the levels of adipsin, ghrelin, glucagon, PAI-1, and visfatin were shown between nBMI and CG. In the case of nBMI and iBMI, statistically significant differences were observed in the concentrations of adiponectin, C-peptide, ghrelin, GLP-1, insulin, leptin, omentin-1, PAI-1, resistin, and visfatin. The obtained results indicate a disruption of endocrine function of adipose tissue and impaired glucose metabolism in HNC. Obesity, which is not a typical risk factor for HNC, may aggravate the negative metabolic changes associated with this type of neoplasm. Ghrelin, visfatin, PAI-1, adipsin, and glucagon might be related to head and neck carcinogenesis. They seem to be promising directions for further research. [ABSTRACT FROM AUTHOR]

Human urinary proteins are a goldmine of natural proteins a feature that simplifies their translation to biologics. Combining this goldmine together with the ligand-affinity-chromatography (LAC) purification method, proved a winning formula in their isolation. LAC specificity, efficiency, simplicity and inherent indispensability in the search for predictable and unpredictable proteins, is superior to other separation techniques. Unlimited amounts of recombinant cytokines and monoclonal antibodies (mAb) accelerated the "triumph". My approach concluded 35 years of worldwide pursuit for Type I IFN receptor (IFNAR2) and advanced the understanding of the signal transduction of this Type of IFN. TNF, IFNγ and IL-6 as baits enabled the isolation of their corresponding soluble receptors and N-terminal amino acid sequence of the isolated proteins facilitated the cloning of their cell surface counterparts. IL-18, IL-32, and heparanase as the baits yielded the corresponding unpredictable proteins: the antidote IL-18 Binding Protein (IL-18BP), the enzyme Proteinase 3 (PR3) and the hormone Resistin. IFNβ proved beneficial in Multiple Sclerosis and is a blockbuster drug, Rebif®. TNF mAbs translated into Remicade® to treat Crohn's disease. Enbrel® based on TBPII is for Rheumatoid Arthritis. Both are blockbusters. Tadekinig alfa™, a recombinant IL-18BP, is in phase III clinical study for inflammatory and autoimmune diseases. Seven years of continuous compassionate use of Tadekinig alfa™ in children born with mutations (NLRC4, XIAP) proved life-saving and is an example of tailored made medicine. IL-18 is a checkpoint biomarker in cancer and IL-18BP is planned recently to target cytokine storms resulting from CAR-T treatment and in COVID 19. [ABSTRACT FROM AUTHOR]

Background: Adipose tissue is not only a storage place for fat, but also an endocrine organ, secreting bioactive molecules which influence body metabolism. Such molecules are known as adipocytokines. In the past years the coincidence between adipocytokines and fetal growth restriction disorders was found. The aim of the study was to estimate serum levels of adiponectin, leptin and resistin in children born small for gestational age, compared to children born at an appropriate size for gestational age. Methods: The study consisted of 35 children aged seven to nine years, born SGA (small for gestational age) on term and 25 healthy children (14 girls, 11 boys), born with proper birthweight (AGA—appropriate for gestational age)–control group. Results: Adiponectin and leptin levels were significantly higher in the SGA group compared to the AGA group (p = 0.023, p = 0.018 respectively). The resistin values were comparable in both groups of patients. There was a positive correlation between serum leptin concentration and current body weight in SGA group (r = 0.28; p = 0.108). In turn, adiponectin levels in this group of patients negatively correlated with actual body weight (r = −0.51; p = 0.002). The negative correlation between body mass index and plasma adiponectin levels was found only in children born SGA. SGA children had significantly higher values of diastolic blood pressure. There was negative correlation between serum adiponectin level and systolic blood pressure in SGA children. In the SGA group the phenomenon of catch-up growth was observed in 32 children. Conclusions: Children born SGA have abnormal adipose tissue biomarkers profiles. [ABSTRACT FROM AUTHOR]

Undiagnosed and untreated non-alcoholic fatty liver disease (NAFLD) can lead to the development of many complications, such as cirrhosis, hepatocellular carcinoma, or cardiovascular diseases. Obese people are at increased risk of developing NAFLD. Due to the current lack of routine diagnostics, it is extremely important to look for new diagnostic methods and markers for this disease. The aim of this study was to assess the concentration of selected pro-inflammatory adipokines and cytokines in the unstimulated saliva of obese people with fatty liver disease in various stages (with or without slight fibrosis) and to analyze them for possible use as early markers of NAFLD diagnosis. The study involved 96 people who were divided into 5 groups based on the criterion of body mass index (BMI) and the degree of fatty liver (liver elastography). There were statistically significant differences between the groups in the concentrations of MMP-9 (matrix metalloproteinase 9), resistin, and IL-1β (interleukin 1β) in saliva. Statistically significant, positive correlations between hepatic steatosis and the concentration of MMP-2 (matrix metalloproteinase 2), resistin, and IL-1β in saliva were also found. Statistically significant positive correlations were also found between the concentration of resistin in saliva and the concentration of ALT (alanine aminotransferase) and GGTP (gamma-glutamyl transpeptidase) in serum. MMP-2, IL-1β, and resistin may be potential markers of NAFLD development, assessed in saliva. However, further research is needed because this is the first study to evaluate the concentrations of the selected pro-inflammatory parameters in the saliva of patients with NAFLD. [ABSTRACT FROM AUTHOR]

Background: The frequent coexistence of obesity and metabolic syndrome in patients with Androgenetic alopecia (AGA), may indicate a common pathogenetic pathway with adipokines being a possible implicating cytokine. Objective: This study was conducted to investigate the changes in serum levels of adipokines, insulin resistance, vitamin D status and their relationship with AGA, and the relationship between serum levels of adipokines and insulin resistance. Methods: 80 male patients with AGA were selected as the experimental group and 60 healthy males served as the control group. Both the AGA group and healthy control group were divided into 2 groups according to the presence or absence of insulin resistance (IR): the IR group and the NIR group. Serum levels of leptin, adiponectin, resistin, visfatin, insulin and 25(OH)D were evaluated in all subjects. Results: Compared with the control group, AGA patients showed higher serum levels of leptin and lower adiponectin/leptin (Adpn/Lep) ratio (P< 0.05), and both were positively correlated with the severity of the disease. Compared with the AGA NIR group, serum leptin levels were increased in the AGA IR group (P< 0.05). AGA IR group and AGA NIR group possessed lower Adpn/Lep ratio when compared with the healthy IR group and healthy NIR group respectively (P< 0.05). The multi-factor logistic regression analysis results showed decreased Adpn/Lep level and increased leptin level as risk factors for AGA. AGA Patients had lower vitamin D levels than healthy controls (P< 0.05). Conclusion: Patients with AGA show an imbalance between pro- and anti-inflammatory adipokines, and probably be involved in AGA pathogenesis. Insulin resistance may influence levels of adipokines, but the present findings cannot indicate insulin resistance plays a role in the onset of AGA. The insufficiency and deficiency of vitamin D are common health concern in our subjects and may be involved in the dysfunction of adipocytes and the development of AGA. [ABSTRACT FROM AUTHOR]

Obesity and overnutrition induce inflammation, leptin-, and insulin resistance in the hypothalamus. The mediobasal hypothalamus responds to exercise enabling critical adaptions at molecular and cellular level that positively impact local inflammation. This review discusses the positive effect of exercise on obesity-induced hypothalamic dysfunction, highlighting the mechanistic aspects related to the anti-inflammatory effects of exercise. In HFD-fed animals, both acute and chronic moderate-intensity exercise mitigate microgliosis and lower inflammation in the arcuate nucleus (ARC). Notably, this associates with restored leptin sensitivity and lower food intake. Exercise-induced cytokines IL-6 and IL-10 mediate part of these positive effect on the ARC in obese animals. The reduction of obesity-associated pro-inflammatory mediators (e.g., FFAs, TNFα, resistin, and AGEs), and the improvement in the gut–brain axis represent alternative paths through which regular exercise can mitigate hypothalamic inflammation. These findings suggest that the regular practice of exercise can restore a proper functionality in the hypothalamus in obesity. Further analysis investigating the crosstalk muscle–hypothalamus would help toward a deeper comprehension of the subject. [ABSTRACT FROM AUTHOR]

Inflammatory rheumatic diseases (IRDs) are complex immune-mediated diseases that are characterized by chronic inflammation of the joints. Rheumatoid arthritis (RA) and spondyloarthritis (SpA), including axial SpA (ax SpA) and psoriatic arthritis (PsA), are the most common forms of IRD. Both RA and ax SpA are characterized by a chronic course with progressive structural modifications, namely, cartilage damage and bone erosions in RA and osteoproliferative changes with spinal ossifications in ax SpA. The adipose tissue is involved in the pathophysiology of IRDs via the release of several proteins, namely, adipokines. Several adipokines with pro-inflammatory effects have been identified, such as leptin, adiponectin, visfatin and resistin. In this review, we discuss the role that adipokines may play in the structural modifications of the peripheral joints and/or axial skeleton. In RA, the role of leptin in structural damage remains controversial, while adiponectin and its high-molecular-weight isoform are known to have an influence on the development of bone erosions and radiographic progression. Resistin also appears to be a potent detrimental adipokine for the joints in RA. In ax SpA, visfatin seems to be an attractive candidate for radiographic progression, while leptin and adiponectin have negative effects on radiographic progression. [ABSTRACT FROM AUTHOR]