Plasma Adipokines Research Articles

Concentration of Polycyclic Aromatic Hydrocarbons (PAHs) in Human Serum and Adipose Tissues and Stimulatory Effect of Naphthalene in Adipogenesis in 3T3-L1 Cells.

Polycyclic aromatic hydrocarbons (PAHs) are one of the most prevalent classes of environmental pollutants. Some evidence shows that PAHs could be involved in human obesity. However, little is known about the distribution patterns of PAHs in human adipose tissue (AT) and the role of PAHs on adipogenesis/lipogenesis. The aims of this pilot study were to determine concentrations of 16 PAHs defined as high-priority pollutants in the plasma and adipose tissue of French and Polish bariatric patients, as well as their correlation with body mass index (BMI), plasma and AT adipokines expression levels. We finally investigated the role of naphthalene on cell proliferation, viability, and differentiation in 3T3-L1 preadipocytes. The concentration of most PAHs was similar in the three types of AT and it was significantly higher in AT as compared to plasma, suggesting bioaccumulation. Polish patients had higher PAH levels in AT than French ones. Only the concentration of naphthalene in AT was positively correlated with the BMI and serum or adipose chemerin, adiponectin and resistin expression, in French but not in Polish patients, who had significantly higher BMIs. Moreover, naphthalene exposure increased the cell proliferation of 3T3-L1 preadipocytes and lipogenesis, and increased the expression of genes involved in adipogenesis after cell differentiation. Taken together, PAHs and more particularly naphthalene could be an obesogenic molecule and increase the risk of obesity.

Circulating adipokine levels and COVID-19 severity in hospitalized patients

BackgroundObesity is a risk factor for adverse outcomes in COVID-19, potentially driven by chronic inflammatory state due to dysregulated secretion of adipokines and cytokines. We investigated the association between plasma adipokines and COVID-19 severity, systemic inflammation, clinical parameters, and outcome of COVID-19 patients.MethodsIn this multi-centre prospective cross-sectional study, we collected blood samples and clinical data from COVID-19 patients. The severity of COVID-19 was classified as mild (no hospital admission), severe (ward admission), and critical (ICU admission). ICU non-COVID-19 patients were also included and plasma from healthy age, sex, and BMI-matched individuals obtained from Lifelines. Multi-analyte profiling of plasma adipokines (Leptin, Adiponectin, Resistin, Visfatin) and inflammatory markers (IL-6, TNFα, IL-10) were determined using Luminex multiplex assays.ResultsBetween March and December 2020, 260 SARS-CoV-2 infected individuals (age: 65 [56–74] BMI 27.0 [24.4–30.6]) were included: 30 mild, 159 severe, and 71 critical patients. Circulating leptin levels were reduced in critically ill patients with a high BMI yet this decrease was absent in patients that were administered dexamethasone. Visfatin levels were higher in critical COVID-19 patients compared to non-COVID-ICU, mild and severe patients (4.7 vs 3.4, 3.0, and 3.72 ng/mL respectively, p < 0.05). Lower Adiponectin levels, but higher Resistin levels were found in severe and critical patients, compared to those that did not require hospitalization (3.65, 2.7 vs 7.9 µg/mL, p < 0.001, and 18.2, 22.0 vs 11.0 ng/mL p < 0.001).ConclusionCirculating adipokine levels are associated with COVID-19 hospitalization, i.e., the need for oxygen support (general ward), or the need for mechanical ventilation and other organ support in the ICU, but not mortality.

Abstract 12892: Cumulative Weight, Adipokines, and Hypertension

Background : Chronic obesity is a major risk factor for hypertension, and obesity-associated hypertension is often difficult to control. Adipokines have vascular effects, but the degree to which they mediate the association between chronic obesity and hypertension is unknown. Methods: We conducted a cross-sectional analysis of 10,842 ARIC participants who attended Visit 3 (1993-95) with self-reported BMI at age 25 and measured BMI at visits 1 to 3 (each 3 years apart). We calculated cumulative excess BMI years by centering BMI at 25 kg/m 2 at each time point and multiplying the mean BMI by the duration in years from age 25 to Visit 3. We categorized cumulative excess BMI years by quartiles. Plasma adipokines (leptin, adiponectin) were measured at Visit 3. Prevalent hypertension at Visit 3 was defined as blood pressure ≥130/80mmHg or hypertension medication use. We used linear regression to assess associations between cumulative BMI quartiles and adipokines (log transformed). We used logistic regression to assess the association of cumulative BMI with prevalent hypertension and the extent to which adipokines mediate this relationship. Results: Higher quartiles of cumulative excess BMI years were associated with lower adiponectin and higher leptin levels (both p&lt;0.001). Higher cumulative excess BMI years was strongly associated with hypertension (OR 2.52 [95% CI 2.21, 2.87], for top vs bottom quartile). Adiponectin partially mediated the association of cumulative excess BMI years with hypertension by 7% (OR for top quartile decreased from 2.52 to 2.41), leptin mediated the association by 18% (OR decreased from 2.52 to 2.24), and the combination of adiponectin and leptin mediated the association by 22% (OR decreased from 2.52 to 2.18) ( Table ). Conclusion: Adipokines may partially mediate the association of long-term excess adiposity with hypertension. Targeting adipokines may have therapeutic value in managing hypertension in those with chronic obesity.

Bone Marrow Adipokine Expression Was Associated With Decreased Erythroid Colony Growth After Trauma.

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. 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. Trauma patients exhibited decreased adiponectin (1.8* vs 3.4mg/mL) and increased leptin (7.8* vs 4.6ng/mL) and resistin (3.1* vs 2.5ng/mL), with sex- and age-specific differences. They also showed increased BM visfatin transcription. Adipokine transcription negatively correlated with erythroid progenitor growth. 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.

An Increase in Plasma Adipsin Levels Is Associated With Higher Cumulative Dust Exposure and Airway Obstruction in Foundry Workers.

The aim of the study was to assess whether plasma adipokine levels (adipsin, adiponectin, leptin, and resistin) are associated with pulmonary function in foundry workers. We examined 65 dust-exposed foundry workers and 40 nonexposed controls and analyzed their lung function and plasma adipokine levels at baseline and after approximately 7 years of follow-up. A higher increase in plasma adipsin was associated with the development of airway obstruction in exposed subjects during follow-up after adjusting for body mass index changes during the follow-up period. Furthermore, the increase in adipsin levels was positively associated with cumulative dust exposure even after adjusting for smoking and body mass index changes during follow-up ( P = 0.015). The results suggest that plasma adipsin is involved in the pathogenesis of subclinical airway inflammation and the development of chronic obstruction and is induced by occupational dust exposure.

Prognostic value of plasma adipokine chemerin in patients with coronary artery disease

BackgroundAdipokine chemerin was proven to be associated with coronary artery disease (CAD), but its prognostic implications in CAD remain unclear.MethodsThis study consists of two parts, one is a basic study and the other is a clinical cohort study. First, we investigated the differential expression of six adipokines in the atherosclerotic mice model compared to mice with milder degrees of atherosclerosis and mice without atherosclerosis using microarray data. We then examined the potential of chemerin as a diagnostic and prognostic indicator in a CAD cohort. A total of 152 patients were enrolled in our study, including 77 patients with angiographically proven CAD and 75 control subjects without cardiovascular disease. Plasma adipokine chemerin levels were measured in all patients, and major adverse cardiovascular events (MACEs) were followed up, including ischemic stroke, non-fatal myocardial infarction, revascularization, and cardiovascular death.ResultsIn the aortas of atherosclerotic mice, chemerin expression was up-regulated compared to control mice. The plasma chemerin levels of CAD patients were higher than those of non-CAD patients (128.93 ± 37.06 vs. 109.85 ± 27.47 mmol/L, respectively, P < 0.001). High chemerin levels were an independent predictor of CAD (β = 2.702, 95% CI, 1.344–5.431, P = 0.001). We followed up with patients for a median duration of 5.5 years (3.9–5.6). The Kaplan–Meier curves showed that patients in the high chemerin group had a significantly higher risk of MACEs than the low chemerin group in patients with CAD (log-rank P = 0.003), not with non-CAD (Log-rank P = 0.120). Furthermore, Cox multivariate analysis revealed that high chemerin levels were an independent predictor of MACEs (HR 2.267; 95% CI, 1.139–4.515; P = 0.020). Finally, the cellular study showed that chemerin is predominantly expressed in PBMC-derived macrophages.ConclusionPlasma chemerin levels were increased in the CAD patients, and a high chemerin level increased the risk of MACEs in CAD patients.

Effects of High-Intensity Interval Training on Selected Adipokines and Cardiometabolic Risk Markers in Normal-Weight and Overweight/Obese Young Males-A Pre-Post Test Trial.

Simple SummaryAdipose tissue secretes bioactive substances called adipokines that affect cardiometabolic health. High-intensity interval training has a beneficial effect on cardiometabolic health, but its impact on adipokines is unclear. This research aims to assess the effects of 8-week high-intensity interval training on plasma levels of four adipokines (leptin, adiponectin, chemerin, and omentin-1) and cardiometabolic risk markers in normal- and excess-weight young males. The findings suggest a beneficial role of adiponectin and omentin, and a harmful role of leptin and chemerin in cardiometabolic health. Following the training, plasma omentin-1 levels had increased in normal- and excess-weight youth, but adiponectin, leptin, and chemerin levels had not changed in both groups. Body mass, fat mass, plasma lipids, and insulin sensitivity improved in excess-weight group, only. Body composition seems not to influence the response of adipokines to high-intensity interval training.The study aimed to assess effects of high-intensity interval training (HIIT) on plasma adipokines and cardiometabolic markers in normal and excess weight youth. Eighteen healthy young males (18.2 ± 1.06 yrs.) were divided in normal-weight group (NWG; body mass index (BMI), 20.5 ± 1.51 kg/m2; n = 9) and excess-weight group (EWG; BMI, 30.8 ± 4.56 kg/m2; n = 9). Participants performed an eight-week HIIT program without caloric restriction. Body composition, plasma leptin, adiponectin, chemerin, omentin-1, lipids, C-reactive protein (CRP), and the homeostasis model assessment index for insulin resistance (HOMA-IR) were assessed before and after the HIIT program. The program resulted in significant increases in omentin levels (p < 0.01) in EWG (27%) and NWG (22%), but no changes in leptin, adiponectin, and chemerin in both groups. BMI (−1.62%; p = 0.015), body fat (−1.59%; p = 0.021), total cholesterol (−11.8%; p = 0.026), triglycerides (−21.3%; p = 0.023), and HOMA-IR (−31.5%; p = 0.043) decreased in EWG only. Repeated measures detected significant interaction “Time x Group” for body mass and BMI only. Eight-week HIIT program improved body composition, lipid profile, and insulin sensitivity in excess-weight individuals. It resulted in an increase in omentin levels in both normal- and excess-weight groups, but no changes in leptin, adiponectin, and chemerin. Body composition has not influenced the response of the four adipokines to HIIT.

Myristic Acid Supplementation Aggravates High Fat Diet-Induced Adipose Inflammation and Systemic Insulin Resistance in Mice.

Saturated fatty acids (SFAs) are considered to be detrimental to human health. One of the SFAs, myristic acid (MA), is known to exert a hypercholesterolemic effect in mice as well as humans. However, its effects on altering adipose tissue (AT) inflammation and systemic insulin resistance (IR) in obesity are still unclear. Here, we sought to determine the effects of a high fat (HF) diet supplemented with MA on obesity-associated metabolic disorders in mice. Wild-type C57BL/6 mice were fed a HF diet in the presence or absence of 3% MA for 12 weeks. Plasma lipids, plasma adipokines, AT inflammation, systemic IR, glucose homeostasis, and hepatic steatosis were assessed. The body weight and visceral adipose tissue (VAT) mass were significantly higher in mice receiving the HF+MA diet compared to HF diet-fed controls. Plasma total cholesterol levels were marginally increased in HF+MA-fed mice compared to controls. Fasting blood glucose was comparable between HF and HF+MA-fed mice. Interestingly, the plasma insulin and HOMA-IR index, a measure of insulin resistance, were significantly higher in HF+MA-fed mice compared to HF controls. Macrophage and inflammatory markers were significantly elevated in the AT and AT-derived stromal vascular cells upon MA feeding. Moreover, the level of circulating resistin, an adipokine promoting insulin resistance, was significantly higher in HF+MA-fed mice compared with HF controls. The insulin tolerance test revealed that the IR was higher in mice receiving the MA supplementation compared to HF controls. Moreover, the glucose tolerance test showed impairment in systemic glucose homeostasis in MA-fed mice. Analyses of liver samples showed a trend towards an increase in liver TG upon MA feeding. However, markers of oxidative stress and inflammation were reduced in the liver of mice fed an MA diet compared to controls. Taken together, our data suggest that chronic administration of MA in diet exacerbates obesity-associated insulin resistance and this effect is mediated in part, via increased AT inflammation and increased secretion of resistin.

Increased liver fat associates with severe metabolic perturbations in low birth weight men.

Ectopic liver fat deposition, resulting from impaired subcutaneous adipose tissue expandability, may represent an age-dependent key feature linking low birth weight (LBW) with increased risk of type 2 diabetes (T2D). We examined whether presumably healthy early middle-aged, non-obese LBW subjects exhibit increased liver fat content, whether increased liver fat in LBW is associated with the severity of dysmetabolic traits and finally whether such associations may be confounded by genetic factors. Using 1H magnetic resonance spectroscopy, we measured hepatic fat content in 26 early middle-aged, non-obese LBW and 22 BMI-matched normal birth weight (NBW) males. Endogenous glucose production was measured by stable isotopes, and a range of plasma adipokine and gut hormone analytes were measured by multiplex ELISA. Genetic risk scores were calculated from genome-wide association study (GWAS) data for birth weight, height, T2D, plasma cholesterol and risk genotypes for non-alcoholic fatty liver disease (NAFLD). The LBW subjects had significantly increased hepatic fat content compared with NBW controls (P= 0.014), and 20% of LBW vs no controls had overt NAFLD. LBW subjects with NAFLD displayed widespread metabolic changes compared with NBW and LBW individuals without NAFLD, including hepatic insulin resistance, plasma adipokine and gut hormone perturbations as well as dyslipidemia. As an exception, plasma adiponectin levels were lower in LBW subjects both with and without NAFLD as compared to NBW controls. Genetic risk for selected differential traits did not differ between groups. Increased liver fat content including overt NAFLD may be on the critical path linking LBW with increased risk of developing T2D in a non-genetic manner.

Gastric Bypass Regulates Early Inflammatory Responses in High-Fat Diet-Induced Obese Mice.

Obesity and diabetes are characterized by chronic inflammatory responses. Roux-en-Y gastric bypass (RYGB) is increasingly regarded as an effective approach for the improvement of glucose homeostasis. In this study, we examined the effects of RYGB on the regulation of early inflammatory responses in the liver and adipose tissue in high-fat diet (HFD)-induced obese (DIO) mice. RYGB was performed in DIO mice followed by analyses of adiposity, insulin sensitivity, plasma and tissue cytokines and adipokines, tissue NF-κB and JNK/c-Jun activation, and tissue macrophage and T-cell subsets. We found that RYGB resulted in sustained improvement of adiposity and insulin sensitivity. Plasma insulin and leptin levels were increased in untreated DIO mice and reduced in RYGB mice. RYGB maintained plasma adiponectin levels and inhibited monocyte chemoattractant protein-1 and interleukin 6 in white adipose tissue (WAT) and liver. RYGB inhibited NF-κB activation in WAT and muscle, but not in the liver. However, RYGB attenuated the JNK/c-Jun signaling pathway in the liver and WAT at 1wk after surgery, suggesting that RYGB regulates the tissue-specific inflammatory pathway. RYGB reduced M1-like (F4/80+/CD11c+) differentiation and enhanced M2-like population (F4/80+/CD206c+). RYGB also regulated CD4+ and CD8+ T-cell infiltration and increased Treg cells in the liver and WAT at the same time point. Our findings demonstrate that RYGB improves obesity and insulin resistance, which are associated with the regulation of early inflammatory reactions in the liver and WAT.

Fitness Levels and Gender Are Related With the Response of Plasma Adipokines and Inflammatory Cytokines in Prepubertal Children.

Background and AimChanges in adipokines have been related with the development of metabolic syndrome, frequently associated with obesity, and other risk factors. Fitness seems to promote a healthy cardiovascular status and could be a protector factor, just from childhood. Therefore, the present study aimed to evaluate the relationship between fitness levels with plasma adipokines and inflammatory biomarkers in prepubertal children.MethodsOne hundred and thirty-seven healthy normal-weight prepubertal children were recruited from local schools and divided after performing the fitness tests, into two groups according to fitness level—low cardiovascular fitness group (LF) and equal or higher cardiovascular fitness group (HF). Anthropometric variables, blood pressure (BP) and plasma insulin, and leptin, resistin, adiponectin, tumor necrosis factor-alpha, hepatic growth factor, interleukin (IL)-8, monocyte chemoattractant protein-1, nerve growth factor (NGF), and plasminogen activator inhibitor-1 (PAI-1) were measured fasting in both groups to be compared. Univariate analysis of variance, comparative analysis, binary logistic regression, stepwise linear regression, and principal component analysis were conducted to evaluate the association between fitness, BMI, gender, and the biochemical parameters.ResultsGirls and boys with HF presented lower waist circumference Z-score, BMI Z-score, systolic BP (only boys) as well as lower levels of leptin and NGF compared with their respective LF group. Regarding the association between variables, fitness showed an inverse relationship with BMI Z-score, leptin, PAI-1, HOMA-IR, resistin, IL-8, and NGF.ConclusionAn adequate level of fitness seems to protect against risk factors related to low-grade inflammation and altered adipokines that are related to the onset of obesity just from the prepubertal stage.

Effect of Insulin Resistance and Role of Plasma Adiponectin Level in Susceptibility to Colorectal Cancer

Background: Despite clinical and basic different investigations, the role of plasma adipokines, such as adiponectin as a precise predictor of the risk of colorectal cancer (CRC) is still conflicting. Aim: This study investigated the association between CRC and insulin resistance, obesity, and plasma adiponectin level for the first time in Iran. Method: A total of 80 subjects (including 45 CRC patients and 35 healthy individuals) were enrolled in this case-control study. Demographic, anthropometric, and clinical data were recorded, and serum levels of adiponectin, insulin, and glucose were evaluated using enzyme-linked immunosorbent assay and glucose oxidase technique, respectively. Insulin resistance index (HOMA-IR) was measured as well. Results: The mean±SD plasma adiponectin concentration of the CRC patients (7.98±0.64 ng/ml) was not significantly higher, compared to that in the control group (8.05±1.14 ng/mL). The mean±SD of HOMA-IR and plasma glucose levels (1.81±0.61 and 7.64±1.34 mm/L, respectively) of the CRC group were significantly higher (P&lt;0.05), compared to the control group (1.37±0.3 and 119±1.1 mg/dL, respectively); however, plasma insulin wasn’t significantly different in the two study groups. Following the stratification of CRC patients according to the tumor site, a significantly lower level of adiponectin (7.36 ±1.1 ng/ml) (P&lt;0.05) and a significantly higher level of HOMA-IR (2.08±0.44) were observed in patients with colon cancer (P&lt;0.005), compared to the controls. Regression among the plasma adiponectin and the plasma insulin and HOMA was negative in the control and CRC groups. Conclusion: Insulin resistance has an important role in the development of CRC, especially in genesis colon cancer, regardless of the change that it causes in plasma levels of adiponectin

Dynamic relationships between body fat and circulating adipokine levels from adolescence to young adulthood: The Santiago Longitudinal Study

Background and aimsAdipose tissue secretes adipokines such as adiponectin and leptin, playing important roles in energy metabolism. The longitudinal associations between such adipokines and body fat accumulation have not been established, especially during adolescence and young adulthood and in diverse populations. The study aims to assess the longitudinal association between body fat measured with dual X-ray absorptiometry and plasma adipokines from adolescence to young adulthood. Methods and resultsAmong Hispanic/Latino participants (N = 537) aged 16.8 (SD: 0.3) years of the Santiago Longitudinal Study, we implemented structural equation modeling to estimate the sex-specific associations between adiposity (body fat percent (BF%) and proportion of trunk fat (PTF)) and adipokines (adiponectin and leptin levels) during adolescence (16 y) and these values after 6 years of follow-up (22 y). In addition, we further investigated whether the associations differed by baseline insulin resistance (IR) status. We found evidence for associations between 16 y BF% and 22 y leptin levels (β (SE): 0.58 (0.06) for females; 0.53 (0.05) for males), between 16 y PTF and 22 y adiponectin levels (β (SE): −0.31 (0.06) for females; −0.18 (0.06) for males) and between 16 y adiponectin levels and 22 y BF% (β (SE): 0.12 (0.04) for both females and males). ConclusionWe observed dynamic relationships between adiposity and adipokines levels from late adolescence to young adulthood in a Hispanic/Latino population further demonstrating the importance of this period of the life course in the development of obesity.

Abstract 13127: Concordance in Nutrient Biomarker and Cardiometabolic Risk Factors Between Child-Parent Dyads Participating in a Family-Based Childhood Weight Management Intervention

Introduction: Children are at elevated risk for developing obesity/cardiometabolic abnormalities when their parents have these conditions. Little is known about diet quality and subsequent impact on cardiometabolic risk factors (CMRFs) in child-parent dyads. Objective: To determine the concordance between nutrient biomarkers and CMRF changes in children (age 7-12 years; BMIz &gt;85%tile) and their parents, who participated in a 1-year randomized controlled trial designed to evaluate the effects of adding an enhanced program to standard care. Methods: Pre-post intervention changes in nutrient biomarkers (plasma carotenoids; RBC fatty acid profiles) and CMRFs (BMI, blood pressure, and plasma glucose, insulin, lipid profile, inflammatory markers and adipokine concentrations) were evaluated in 226 child-parent dyads. Based on percent change in children’s BMIz score, they were grouped into high ( &gt; -8%), medium (0 to -8%) and low ( &gt; 0%) responders. Spearman’s correlation coefficients were calculated to determine association between 1-year change in nutrient biomarkers and CMRFs within child-parent dyad groups. Results: There were positive associations in beta-carotene, and RBC SFA, MUFA, PUFA n-6, PUFA n-3 and trans fatty acid concentrations in child-parent dyads, regardless of group ( r= 0.25 to 0.83, p&lt;0.05). Significant positive child-parent associations were observed for systemic (TNFa, IL-1, IL-6) and vascular (E- and P-selectin, thrombomodulin) inflammatory markers (r= 0.32 to 0.83, p&lt;0.05), and adiponectin (r=0.47, p=0.001), but not other CMRFs. In the high responder group, there was a positive association between improvements in child’s BMIz scores and parental BMI (r=0.32, p=0.01). This dyad also had the most favorable improvements in nutrient biomarkers (increases in carotenoids, and decreases in SFA and trans fatty acids) and CMRFs (decreases in blood pressure, and LDL-C, TG and hsCRP concentrations). Conclusions: Our finding of concordance in child-parent dyad changes in nutrient biomarkers and selected CMRFs after a 1-year intervention, especially in the high responder group, suggests parallel dietary changes and highlights the importance of parental engagement in the effectiveness of childhood obesity interventions.

Science for Kids:Effects of low-glycemic index diet on plasma adipokines in childhood obesity.

Science for Kids:Effects of low-glycemic index diet on plasma adipokines in childhood obesity.

The Effect of Resveratrol on Blood Glucose and Blood Lipids in Rats with Gestational Diabetes Mellitus.

Background Previous studies have reported that resveratrol has various biological effects such as anti-inflammatory, antioxidant, and antitumor. This study aimed to investigate the effects of resveratrol on blood glucose and blood lipids in rats with gestational diabetes mellitus (GDM). Methods The rat diabetes model was prepared by one-time intraperitoneal injection of streptozotocin (STZ, 35 mg/kg). Fasting blood glucose was measured by using a blood glucose meter. The ELISA method was used to detect the levels of insulin, leptin, adiponectin, resistin, TNF-α, and IL-6. The content of TC, TG, LDL-C, and HDL-C was determined by using an automatic biochemical detector. Results Compared with the GDM group, the insulin level in the resveratrol (120 and 240 mg/kg) treatment group was significantly increased. But, the blood glucose level and body weight were significantly reduced. The content of TC, TG, and LDL-C in the resveratrol (240 mg/kg) treatment group was significantly reduced, and the content of HDL-C was significantly increased. In addition, leptin, resistin, TNF-α, and IL-6 levels in the 240 mg/kg resveratrol treatment group were significantly reduced, and adiponectin was significantly increased. Also, resveratrol (240 mg/kg) was stronger than metformin hydrochloride in improving insulin secretion and regulating blood lipids and adipokine content. Conclusion Resveratrol has a dose-dependent effect on GDM rats to increase insulin secretion, reduce blood glucose and body weight, and regulate blood lipids and plasma adipokines.

P–653 The levels and ratios of adipokines in the follicular fluid as promising prognostic factors for in vitro fertilization outcomes

Abstract Study question Can the adipokines levels and ratios in the follicular fluid (FF) be used to predict in vitro fertilization (IVF) outcomes? Summary answer The leptin level and ratios leptin/ghrelin and leptin/adiponectin in FF are reliable prognostic factors for IVF outcomes in women with normal body mass index (BMI). What is known already The adipose tissue serves not a simple fat storage, rather an important endocrine organ, producing adipokines, such as leptin, adiponectin, ghrelin and others. Adipokines have been shown to regulate the cardiovascular system, food intake, metabolism, inflammation, metastatic spread of tumors,and also reproduction, affecting the activity of the hypothalamo-pituitary-gonadal axis. The plasma and FF adipokines have been used as prognostic factors for IVF outcomes, but the obtained results are controversial. The most promising in this case may be the distribution of patients into groups in accordance with their BMI and a separate study of adipokine ratios in them. Study design, size, duration Women (n = 53), who undergo IVF, were divided on two groups, according to their BMI: normal BMI (18.5–24.9 kg/m2, n = 25) and increased BMI (&amp;gt;25.0 kg/m2, n = 28). Depending on IVF outcomes after the antagonist protocol, the groups formed were subsequently subdivided into two groups each: non-pregnant with normal BMI (nPN, n = 16), pregnant with normal BMI (PN, n = 9), non-pregnant with increased BMI (nPI, n = 21), pregnant with increased BMI (PI, n = 7). Participants/materials, setting, methods: Inclusion criteria for participants were: age 18–45 years and infertility due to male/tubal factor. Exclusion criteria were: polycystic ovarian syndrome (PCOS), diabetes mellitus, or plasma level of anti-Müllerian hormone &amp;lt;1.0 ng/mL. The FF from the first punctated follicle was collected and tested for leptin, adiponectin and ghrelin levels using ELISA kits. If gestational sac was seen in uterine cavity using ultrasound on day 21–25 after embryo transfer, pregnancy was diagnosed. Main results and the role of chance Women with increased BMI had, as a rule, higher FF levels of leptin and the leptin/ghrelin and leptin/adiponectin ratios, compared with women with normal BMI. Furthermore, leptin level was higher in PN as compared to nPN (21.61±2.55 vs 10.54±1.16, p &amp;lt; 0.05), but did not differ in the PI and nPI groups. The same pattern was obtained for the leptin/ghrelin and leptin/adiponectin ratios. The ghrelin level showed an inverse pattern. It was higher in nPN as compared to PN (3.80±0.78 vs 1.39±0.19, p &amp;lt; 0.05), but did not differ in women with increased BMI. The obtained data demonstrate that the association between the adipokine levels in FF and the IVF outcomes is better in women with normal BMI than in women with increased BMI. Adipokines, which differed among the study groups, were evaluated as prognostic factors in women with normal BMI.The values were calculated at which pregnancy became unlikely: leptin level &amp;lt;15 ng/mL, leptin/ghrelin ratio &amp;lt;9, and leptin/adiponectin ratio &amp;lt;5. For each indicators, the sensitivity and specificity were &amp;gt;88%. The predictive power of these indicators in the clinic using the odds ratio (95% confidence interval) was: leptin level 7.11 (1.23–40.99, p &amp;lt; 0.05), leptin/ghrelin 29.53 (1.53–570.83, p &amp;lt; 0.05), and leptin/adiponectin 7.11 (1.23–40.99, p &amp;lt; 0.05). Limitations, reasons for caution The main limitation of the study is a relative small number of patients, although the differences between the investigated groups were significant. Furthermore, women with low ovarian reserve, age &amp;gt; 40 years, endometriosis or PCOS were not included in the study. Wider implications of the findings: The obtained results indicate the good prospects for using such indicators as the adipokines levels and their ratio in FF to predict IVF outcomes in women with low ovarian reserve, endometriosis and PCOS, but with normal BMI. Trial registration number Not applicable

Exploratory Analysis in the Differences in Blood Serum and Seminal Plasma of Adipose-Tissue Related Peptides in Obese and Non-Obese Men and Their Correlations With Semen Parameters.

ObjectivesEvaluating the relationship between circulating metabolic biomarkers and semen parameters in obese, overweight and normal-weight patients.MethodsPatients were recruited at the “Andrology and Pathophysiology of Reproduction Unit”, in Santa Maria Goretti Hospital. Divided into three groups were 98 participants (obese, overweight and normal-weight patients) according to BMI and were analyzed for three adipokines and six hormone peptides in blood serum and seminal plasma using Luminex assay. Standard semen analysis was performed for ejaculate volume, sperm concentration, total sperm count, motility, morphology and leukocytes.ResultsIn all groups of subjects, we observed a higher concentration of blood serum c-peptide, GIP, PAI-1, leptin, ghrelin and GLP-1 in comparison to seminal plasma; differently, higher levels in seminal plasma were observed for insulin and visfatin. In comparison to the non-obese subjects, obese subjects showed a higher blood serum concentration of c-peptide, GLP-1, GIP and leptin and a higher concentration of seminal plasma of GIP and insulin. Total sperm count, progressive motility, motility, and atypical forms directly correlated with PAI-1 and visfatin, whereas GLP-1 directly correlated only with total progressive motility.ConclusionObese men showed a different pattern of blood serum and seminal plasma adipokines and hormone peptides concentrations in comparison to normal-weight men. Furthermore, these molecules correlated with functional seminal parameters. Our findings support the option to consider these molecules as new biomarkers and pharmacological targets for a new therapeutic approach in male infertility. However, further studies identifying other potential biomarkers of male infertility with important clinical implication and characterizing their mechanisms of action are mandatory.

Toll-like receptor 3 ablation prevented high-fat diet-induced obesity and metabolic disorder

Inflammation in insulin-sensitive tissues (e.g., liver, visceral adipose tissue [VAT]) plays a major role in obesity and insulin resistance. Recruitment of innate immune cells drives the dysregulation of glucose and lipid metabolism. We aimed to seek the role of Toll like receptor 3 (TLR3), a pattern recognition receptor involved in innate immunity, obesity and the metabolic disorder. TLR3 expression in liver and VAT from diet induced obese mice and in VAT from overweight women was examined. Body weight, glucose homeostasis and insulin sensitivity were evaluated in TLR3 wild-type and knockout (KO) mice on a chow diet (CD) or high-fat diet for 15 weeks. At euthanasia, blood was collected, and plasma biochemical parameters and adipokines were determined with commercial kits. Flow cytometry was used to measure macrophage infiltration and activation in VAT. Standard western blot, immunohistochemistry and quantative PCR were used to assess molecules in pathways about lipid and glucose metabolism, insulin and inflammation in tissues of liver and VAT. Utilizing human and animal samples, we found that expression of TLR3 was upregulated in the liver and VAT in obese mice as well as VAT in overweight women. TLR3-deficiency protected against high-fat diet induced obesity, glucose intolerance, insulin resistance and lipid accumulation. Lipolysis was enhanced in VAT and hepatic lipogenesis was inhibited in TLR3 KO animals. Macrophages infiltration into adipose tissue was attenuated in TLR3 KO mice, accompanied with inhibition of NF-κB-dependent AMPK/Akt signaling pathway. These findings demonstrated that TLR3 ablation prevented obesity and metabolic disorders, thereby providing new mechanistic links between inflammation and obesity and associated metabolic abnormalities in lipid/glucose metabolism.

Are adipokines the missing link between obesity, immune response, and outcomes in severe COVID-19?

IntroductionObesity is commonly reported in COVID-19 patients and is associated with poorer outcomes. It is suggested that leptin could be the missing link between obesity and severe COVID-19. Our study aimed to unravel the link between adipokines, COVID-19 status, immune response, and outcomes in severe pneumonia.MethodsIn this prospective observational single-center study, 63 immunocompetent patients with severe pneumonia (36 non-COVID-19 and 27 COVID-19) were enrolled, most required intensive care. Clinical and biological characteristics (glucose metabolism, plasma adipokines, and cytokine concentrations) and outcomes were compared.ResultsAt similar baseline severity, COVID-19 patients required mechanical ventilation for significantly longer than non-COVID-19 patients (p = 0.0049). Plasma concentrations of leptin and adiponectin were respectively positively and negatively correlated with BMI and glucose metabolism (glycemia and insulinemia), but not significantly different between the two groups. Leptin levels were negatively correlated with IL-1β and IL-6, but the adipokines were not correlated with most other inflammatory mediators, baseline severity (SOFA score), or the duration of mechanical ventilation.ConclusionAdipokine levels were correlated with BMI but not with most inflammatory mediators, severity, or outcomes in severe pneumonia, regardless of the origin. The link between obesity, dysregulated immune response, and life-threatening COVID-19 requires further investigation.Clinical trialClinicalTrials.gov: NCT03505281.