Circulating Levels Of Adipokines Research Articles

Effect of Fibrate Treatment on Circulating Adipokine Levels: A Systematic Review and Meta-analysis of Randomized Clinical Trials

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

The Variants in ADIPOQ are Associated with Maternal Circulating Adipokine Profile in Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is the most common association with hyperglycemia and glucose intolerance during pregnancy. The adipokines play an important to control insulin secretion and glucose. This study aimed to investigate the association between maternal circulating adipokine levels and ADIPOQ gene polymorphism among pregnant women subjects with GDM and normal glucose tolerance (NGT). Participants including 229 normal pregnant women and 197 GDM pregnant women were enrolled from 2015 to 2018 at Siriraj hospital. Serum adipokine levels including adiponectin, adipsin/factor D, NGAL/Lipocalin-2, total PAI-1, and resistin were measured by immunoassay. ADIPOQ variations were investigated including -11377C/G (rs266729), +45T/G (rs2241766), and +276G/T (rs1501299). Serum adiponectin concentration was also significantly decreased among the GDM who had aged less than 35 years old whereas adipsin levels were significantly lower among the GDM who had aged more than 35 years old. Also, adiponectin and total PAI-1 levels were significantly lower among the GDM who had a BMI of less than 30 kg/m2. The G allele frequency of ADIPOQ +45T/G was significantly different between GDM and controls (p = 0.03). ADIPOQ +45T/G was associated with an increased risk of GDM (odds ratio [OR]: 1.554; 95% confidence interval [CI]: 1.010-2.390; p=0.045). The -11377C/G was affected by the level of adiponectin (p = 0.04). The C allele of -11377C/G SNP declined serum adiponectin levels and may be a risk factor for GDM. This study revealed that genetics play important roles in circulating adipokines among pregnant women. ADIPOQ polymorphisms had significant associations with adiponectin levels in GDM patients.

Relationship between circulating adipokines and cholesterol efflux in subjects with severe carotid atherosclerosis

AimsCholesterol efflux capacity (CEC) as a measure of high-density lipoprotein functionality is independently and inversely associated with increased risk of cardiovascular events and mortality, and advanced plaque morphology. Adipokines, adipose tissue-derived factors, can influence systemic lipoprotein metabolism, and participate in the regulation of vascular function and inflammation. We aimed to investigate the association between CEC and circulating adipokine levels (anti-inflammatory adiponectin, and pro-inflammatory chemerin and resistin) in subjects with severe carotid atherosclerotic disease and evaluate its impact on post-surgical outcomes. Methods and resultsThis is a cross-sectional study with a 5-year follow-up component. Consecutive patients with severe carotid atherosclerosis scheduled for a carotid endarterectomy were recruited from hospital-based centres in Montreal, Canada (n = 285). Fasting blood samples were collected pre-operatively and used to measure plasma total and high-molecular weight (HMW) adiponectin, chemerin, and resistin, and to perform cholesterol efflux assays in J774 macrophage-like cells. Five-year post-surgery outcomes were obtained through medical chart review. Subjects had a mean age of 70.1 ± 9.4, were 67.0 % male, had various comorbidities (hypercholesterolemia [85.3 %], hypertension [83.5 %], type 2 diabetes [34.5 %], coronary artery disease [38.6 %]), and previously experienced cerebrovascular symptomatology (77.9 %). CEC was independently and positively associated with total and HMW adiponectin levels (ß [95 % confidence interval]; 0.216 [0.134–0.298] and 0.107 [0.037–0.176], respectively) but not with chemerin or resistin. Total adiponectin had the greatest association accounting for 8.3 % of the variance in CEC. Interaction regression models demonstrated a significant interaction between adiponectin and chemerin in increasing CEC. Notably, with each unit increase in CEC there was a 93.9 % decrease in the odds of having an ischemic cerebrovascular event 5 years post-surgery (0.061 [0.007–0.561]). ConclusionsOur findings demonstrated circulating adiponectin to have a strong association with increased CEC in subjects with severe carotid atherosclerosis and high CEC to be associated with more favourable post-surgical outcomes. These findings reflect the importance of adipose tissue health in influencing CEC levels and atherosclerotic cardiovascular disease risk.

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.

Association between adipokines and cardiac remodeling in obese patients in preclinical heart failure

Introduction. Association of left ventricular hypertrophy (LVH) in obesity and accompanying metabolic risks with adipokines levels at the different stage of heart failure (HF) is still debatable.The aim of study was to investigate the relationship of circulating adipokines levels with LVH in obese patients at preclinical stage of HF.Materials and methods. The study included 74 obese patients: 43% had no markers of LVH (stage A HF, group 1); 57% had LVH (stage B HF, group 2). Transthoracic echocardiography, laboratory assessment of N-terminal fragment of the brain natriuretic peptide, soluble suppression of tumorigenesis-2 (sST2), circulating leptin and adiponectin levels, homeostasis model assessment of insulin resistance (IR) (HOMA-IR) were done. Matched-pairs analysis was applied.Results. Negative correlations of LVH with leptin levels in group 1 (stage A HF) and with adiponectin levels in group 2 (stage B HF) were detected (all p &lt; 0.05). Positive correlations of the sST2 / adiponectin ratio and HOMA-IR with the parameters of LVH were detected in group 2 (all p &gt;&lt; 0.05). Conclusion. The direction of the associations between circulating adipokines and LVH varies with the preclinical stage of HF. The data obtained may reflect a relationship between heart remodeling in response to molecular mechanisms of inflammation and IR in obese patients at the certain stage of cardiovascular continuum. Keywords: leptin, adiponectin, insulin resistance, HOMA-IR, inflammation, sST2, left ventricular hypertrophy&gt;˂ 0.05). Positive correlations of the sST2 / adiponectin ratio and HOMA-IR with the parameters of LVH were detected in group 2 (all p ˂ 0.05).Conclusion. The direction of the associations between circulating adipokines and LVH varies with the preclinical stage of HF. The data obtained may reflect a relationship between heart remodeling in response to molecular mechanisms of inflammation and IR in obese patients at the certain stage of cardiovascular continuum.

Hypothalamic AAV-BDNF gene therapy improves metabolic function and behavior in the Magel2-null mouse model of Prader-Willi syndrome

Individuals with Prader-Willi syndrome (PWS) display developmental delays, cognitive impairment, excessive hunger, obesity, and various behavioral abnormalities. Current PWS treatments are limited to strict supervision of food intake and growth hormone therapy, highlighting the need for new therapeutic strategies. Brain-derived neurotrophic factor (BDNF) functions downstream of hypothalamic feeding circuitry and has roles in energy homeostasis and behavior. In this preclinical study, we assessed the translational potential of hypothalamic adeno-associated virus (AAV)-BDNF gene therapy as a therapeutic for metabolic dysfunction in the Magel2-null mouse model of PWS. To facilitate clinical translation, our BDNF vector included an autoregulatory element allowing for transgene titration in response to the host’s physiological needs. Hypothalamic BDNF gene transfer prevented weight gain, decreased fat mass, increased lean mass, and increased relative energy expenditure in female Magel2-null mice. Moreover, BDNF gene therapy improved glucose metabolism, insulin sensitivity, and circulating adipokine levels. Metabolic improvements were maintained through 23 weeks with no adverse behavioral effects, indicating high levels of efficacy and safety. Male Magel2-null mice also responded positively to BDNF gene therapy, displaying improved body composition, insulin sensitivity, and glucose metabolism. Together, these data suggest that regulating hypothalamic BDNF could be effective in the treatment of PWS-related metabolic abnormalities.

Circulating adipokine levels and preeclampsia: A bidirectional Mendelian randomization study.

Background: Several observational studies have demonstrated that significantly rising circulating adipokine levels are pervasive in preeclampsia or eclampsia disorder (or preeclampsia toxemia (PET)). However, it remains unclear whether this relationship is causal. In this study, we sought to elucidate the causal effects of circulating adipokine levels on PET. Methods: Summary-level data and independent genetic variants strongly associated with common adipokine molecule (adiponectin, leptin, resistin, sOB-R, and PAI-1) levels were drawn from public genome-wide association study (GWASs). Additionally, the corresponding effects between instrumental variables and PET outcomes were acquired from the FinnGen consortium, including 4,743 cases and 136,325 controls of European ancestry. Subsequently, an inverse-variance weighted (IVW) approach was applied for the principal two-sample Mendelian randomization (MR) and multivariable MR (MVMR) analyses. Various complementary sensitivity analyses were then carried out to determine the robustness of our models. Results: The results of the IVW method did not reveal any causal relationship shared across genetically predisposed adipokine levels and PET risk (for adiponectin, OR = 0.86, 95% CI: 0.65–1.13, p = 0.274). Additionally, no significant associations were identified after taking into account five circulating adipokines in MVMR research. Complementary sensitivity analysis also supported no significant associations between them. In the reverse MR analysis, genetically predicted PET risk showed a suggestive association with elevating PAI-1 levels by the IVW method (Beta = 0.120, 95% CI: 0.014, 0.227, p = 0.026). Furthermore, there were no strong correlations between genetic liability to PET and other adipokine levels (p > 0.05). Conclusion: Our MR study did not provide robust evidence supporting the causal role of common circulating adipokine levels in PET, whereas genetically predicted PET may instrumentally affect PAI-1 levels. These findings suggest that PAI-1 may be a useful biomarker for monitoring the diagnosis or therapy of PET rather than a therapeutic target for PET.

Production of Reactive Oxygen Species by Epicardial Adipocytes Is Associated with an Increase in Postprandial Glycemia, Postprandial Insulin, and a Decrease in Serum Adiponectin in Patients with Severe Coronary Atherosclerosis.

Purpose. This work investigates the relations between the production of reactive oxygen species (ROS) by epicardial adipose tissue (EAT) adipocytes and parameters of glucose/insulin metabolism, circulating adipokines levels, and severity of coronary atherosclerosis in patients with coronary artery disease (CAD); establishing significant determinants describing changes in ROS EAT in this category of patients. Material and methods. This study included 19 patients (14 men and 5 women, 53–72 y.o., 6 patients with diabetes mellitus type 2; 5 patients with prediabetes), with CAD, who underwent coronary artery bypass graft surgery. EAT adipocytes were isolated by the enzymatic method from intraoperative explants obtained during coronary artery bypass grafting. The size of EAT adipocytes and ROS level were determined. Results. The production of ROS by EAT adipocytes demonstrated a direct correlation with the level of postprandial glycemia (rs = 0.62, p < 0.05), and an inverse correlation with serum adiponectin (rs = −0.50, p = 0.026), but not with general and abdominal obesity, EAT thickness, and dyslipidemia. Regression analysis demonstrated that the increase in ROS of EAT adipocytes occurs due to the interaction of the following factors: postprandial glycemia (β = 0.95), postprandial insulin (β = 0.24), and reduced serum adiponectin (β = −0.20). EAT adipocytes in patients with diabetes and prediabetes manifested higher ROS production than in patients with normoglycemia. Although there was no correlation between the production of ROS by EAT adipocytes and Gensini score in the total group of patients, higher rates of oxidative stress were observed in EAT adipocytes from patients with a Gensini score greater than median Gensini score values (≥70.55 points, Gr.B), compared to patients with less severe coronary atherosclerosis (<70.55 points, Gr.A). Of note, the frequency of patients with diabetes and prediabetes was higher among the patients with the most severe coronary atherosclerosis (Gr.B) than in the Gr.A. Conclusions. Our data have demonstrated for the first time that systemic impairments of glucose/insulin metabolism and a decrease in serum adiponectin are significant independent determinants of oxidative stress intensity in EAT adipocytes in patients with severe coronary atherosclerosis. The possible input of the interplay between oxidative stress in EAT adipocytes and metabolic disturbances to the severity of coronary atherosclerosis requires further investigation.

Implications of Adipose Tissue Content for Changes in Serum Levels of Exercise-Induced Adipokines: A Quasi-Experimental Study.

Human adipocytes release multiple adipokines into the bloodstream during physical activity. This affects many organs and might contribute to the induction of inflammation. In this study, we aimed to assess changes in circulating adipokine levels induced by intense aerobic and anaerobic exercise in individuals with different adipose tissue content. In the quasi-experimental study, 48 male volunteers (aged 21.78 ± 1.98 years) were assigned to groups depending on their body fat content (BF): LBF, low body fat (<8% BF, n = 16); MBF, moderate body fat (8–14% BF, n = 19); and HBF, high body fat (>14% BF, n = 13). The volunteers performed maximal aerobic effort (MAE) and maximal anaerobic effort (MAnE) exercises. Blood samples were collected at five timepoints: before exercise, immediately after, 2 h, 6 h, and 24 h after each exercise. The selected cytokines were analyzed: adiponectin, follistatin-like 1, interleukin 6, leptin, oncostatin M, and resistin. While the participants’ MAnE and MAE performance were similar regardless of BF, the cytokine response of the HBF group was different from that of the others. Six hours after exercise, leptin levels in the HBF group increased by 35%. Further, immediately after MAnE, resistin levels in the HBF group also increased, by approximately 55%. The effect of different BF was not apparent for other cytokines. We conclude that the adipokine exercise response is associated with the amount of adipose tissue and is related to exercise type.

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.

Soy isoflavone ameliorated the alterations in circulating adipokines and microRNAs of mice fed a high-fat diet.

Soy protein, containing isoflavones and bioactive peptides, is shown to have anti-obesity effects, but the main contributor and underlying mechanisms remain unclear. Recent studies have demonstrated that circulating microRNAs (miRNAs) act as important mediators in obesity and metabolic processes. In this study, we investigated whether soy protein components have distinctive effects on adiposity and circulating miRNA profiles in obese mice. C57BL/6J mice were divided into 4 groups, and each group was fed with a control, high-fat (HF), HF with low-isoflavone soy protein (HF/S), or HF with high-isoflavone soy protein (HF/SI) diet for 16 weeks. In the HF/SI group, changes in the serum adipokine levels, adipocyte diameter, and the number of crown-like structures (CLS) were alleviated compared to those of the HF group. In the HF/S group, the number of CLS was reduced. Decreases in body and adipose tissue weights were not observed in both HF/S and HF/SI groups. Through microarray analysis of serum miRNAs, we identified 23 differentially expressed miRNAs (DEMs) among the groups. The levels of most circulating DEMs were correlated with body weight, serum biochemical parameters, and adipose tissue histology. Functional analysis of predicted target genes of DEMs from both HF vs. CON and HF/S vs. CON comparisons revealed several cancer-related pathways. Only 2 DEMs were identified in the HF/SI vs. CON comparison. In conclusion, the present study confirmed that soy isoflavones are the main contributor to the health-beneficial effects of soy protein in diet-induced obesity. Notably, the extent of serum miRNA dysregulation coincided with obesity and altered the circulating adipokine levels. These findings provide additional insights into the role of soy protein in the regulation of circulating miRNAs in diet-induced obesity. Further work is required to validate the proposed functions of miRNAs in target tissues.

Circulating Adipokine Levels in Nonobese Women With Polycystic Ovary Syndrome and in Nonobese Control Women: A Systematic Review and Meta-Analysis.

Levels of circulating adipokines in nonobese polycystic ovary syndrome (PCOS) patients have been reported in many studies. However, the results are inconsistent. The aim of this meta-analysis is to assess whether the levels of circulating adipokines are changed in nonobese PCOS relative to nonobese healthy controls. To identify eligible studies, a literature research was performed in the PubMed, Embase, and Web of Science databases without restricting by region, journal, or language. A total of 81 studies met the eligibility criteria. The meta-analysis showed that the circulating level of adiponectin (standardized mean difference [SMD]: -0.95; 95% CI: -1.36 to -0.53) was significantly decreased in nonobese PCOS patients. In contrast, the circulating levels of chemerin (SMD: 1.13; 95% CI: 0.08 to 2.18), leptin (SMD: 0.47; 95% CI: 0.13 to 0.81), resistin (SMD: 0.45; 95% CI: 0.03 to 0.88), and visfatin (SMD: 1.38; 95% CI: 0.68 to 2.09) were significantly increased in nonobese PCOS patients. There were no significant changes in the circulating levels of apelin (SMD: 0.32; 95% CI: -1.34 to 1.99), irisin (SMD: 1.01; 95% CI: -0.68 to 2.70), omentin (SMD: -0.37; 95% CI: -1.05 to 0.31), or vaspin (SMD: 0.09; 95% CI: -0.14 to 0.32). Thus, scientific evidence suggests that the circulating adipokine levels are altered in nonobese PCOS patients compared to nonobese healthy controls. Therefore, independent of the degree of obesity, dysregulated circulating adipokine levels might play important roles in the occurrence and development of PCOS.

The Variants in &lt;i&gt;ADIPOQ&lt;/i&gt; Are Associated with Maternal Circulating Adipokine Profile in Gestational Diabetes Mellitus

Background: Gestational diabetes mellitus (GDM) is the most common association with hyperglycemia and glucose intolerance during pregnancy. The role of adipokines plays importantly to control insulin secretion and glucose. This study aimed to investigate the association between maternal circulating adipokine levels and ADIPOQ gene polymorphism among pregnant women subjects with gestational diabetes mellitus (GDM) and normal glucose tolerance (NGT). Methods: Participants including 229 normal pregnant women and 197 GDM pregnant women were enrolled from 2015 to 2018 at Siriraj hospital. Serum adipokine levels including adiponectin, adipsin/factor D, NGAL/Lipocalin-2, total PAI-1, and resistin were measured by immunoassay. ADIPOQ variations (-11377C/G, +45T/G and +276G/T) were investigated. Results: Serum adiponectin concentration was also significantly decreased among the GDM who had age less than 35 years old whereas adipsin levels were significantly lower among the GDM who had aged more than 35 years old. Also, adiponectin, and total PAI-1 levels were significantly lower among the GDM who had a BMI of less than 30 kg/m2. Variants of ADIPOQ +45T/G were significantly associated with disease status (p=0.03). The -11377C/G was affected by the level of adiponectin (p=0.04). The C allele of -11377C/G SNP was declined serum adiponectin levels and may be a risk factor for GDM. Conclusion: This study revealed that genetic play important roles in circulating adipokines among pregnant women. ADIPOQ polymorphisms had significant associations with adiponectin levels in GDM patients. Funding Information: This research project was supported by Siriraj Research Grant for Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University to WT (grant no. R015934014) and TN. Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: This cross-sectional study was approved by the Faculty of Medicine Siriraj hospital ethics review board, Mahidol University, Thailand (Si 577/2015). The written informed consent was obtained from all subjects.

Altered circulating adipokines and heart rate variability: A biomarker for autonomic imbalance in obese individuals

Background: Evidences indicate altered circulating adipokine levels in obesity could increase the risk for cardiovascular disease (CVD). Hence, it is crucial to determine cardiovascular health by assessing heart rate variability (HRV) and its association with circulating adipokines. Aim and Objectives: The aim of the study was to assess the adipokines level and its association with HRV in obese population. Materials and Methods: A cross-sectional comparative study was conducted on 45 obese (body mass index [BMI] > 25–29.9 kg/m2) and 45 non-obese (BMI: 18.5–22.9 kg/m2) age-gender-matched participants. Lead-II electrocardiogram was recorded and HRV parameters were obtained. Biochemical parameters, that is, fasting blood glucose, fasting insulin, HOMA-IR, lipid profile, leptin, and adiponectin levels were estimated. Group comparisons were done by independent student’s t-test, whereas the association between the parameters was done by Pearson’s correlation using SPSS 20v. P < 0.05 was considered statistically significant. Results: There was a significant increase in low frequency: high frequency (LF: HF) ratio (

Crude extract of Camellia oleifera pomace ameliorates the progression of non-alcoholic fatty liver disease via decreasing fat accumulation, insulin resistance and inflammation.

Consumption of a high-fat diet increases fat accumulation and may further lead to inflammation and hepatic injuries. The aim of the study was to investigate the effects of Camellia oleifera seed extract (CSE) on non-alcoholic fatty liver disease (NAFLD). After a 16-week NAFLD-inducing period, rats were assigned to experimental groups fed an NAFLD diet with or without CSE. At the end of the study, we found that consuming CSE decreased the abdominal fat weight and hepatic fat accumulation and modulated circulating adipokine levels. We also found that CSE groups had lower hepatic cytochrome P450 2E1 and transforming growth factor (TGF)-β protein expressions. In addition, we found that CSE consumption may have affected the gut microbiota and reduced toll-like receptor (TLR)-4, myeloid differentiation primary response gene 88, toll/IL-1 receptor domain-containing adaptor-inducing interferon-β (TRIF) expression and proinflammatory cytokine concentrations in the liver. Our results suggest that CSE may alleviate the progression of NAFLD in rats with diet-induced steatosis through reducing fat accumulation and improving lipid metabolism and hepatic inflammation.

The role of adipokines in the improvement of diabetic and cardiovascular risk factors within a 52-week weight-loss programme for obesity

BackgroundObesity is an independent risk factor for cardiovascular disease and diabetes weight reduction not only reduces the risk for these diseases but leads to an alteration of the circulating adipokine levels. The aim of our study was to evaluate the effect of weight loss and lifestyle changes implemented in the form of the interdisciplinary weight management programme Optifast52® on cardiovascular and diabetic risk factors and on key adipokines. Methods72 morbidly obese patients were included in the programme, which consisted of a very low-calorie diet followed by incremental food introduction and dietary stabilisation, accompanied by medical surveillance, physical activity, dietary counselling and psychological support. At baseline, and after 14, 26 and 49 weeks, risk factor profiles and adipokine levels were evaluated. Results43 patients completed the programme with an average weight reduction of about 20%. Significant improvement was observed in the lipid and diabetic laboratory panels of all patients. In addition, adiponectin levels increased significantly (7.79 vs. 12.38μg/ml, p<0.001), while leptin levels decreased (7.29 vs 3.09ng/ml, p<0.001) during the course of the programme. ConclusionIn this study, Optifast52®, a multidisciplinary programme focusing on diet and lifestyle changes, was found not only to affect a decrease in parameters associated with diabetes and cardiovascular disease, but also to ameliorate in part the obesity-related imbalance of pro- and anti-inflammatory adipokines.

Prediction of Circulating Adipokine Levels Based on Body Fat Compartments and Adipose Tissue Gene Expression

Background: Adipokines are hormones secreted from adipose tissue (AT), and a number of them have been established as risk factors for chronic diseases. However, it is not clear whether and to what extent adiposity, gene expression, and other factors determine their circulating levels. Objectives: To assess to what extent adiposity, as measured by the amount of subcutaneous AT (SAT) and visceral AT (VAT) using magnetic resonance imaging, and gene expression levels in SAT determine plasma concentrations of the adipokines adiponectin, leptin, soluble leptin receptor, resistin, interleukin 6, and fatty acid-binding protein 4 (FABP4). Methods: We performed a cross-sectional analysis of 156 participants from the EPIC Potsdam cohort study and analyzed multiple regression models and partial correlation coefficients. Results: For leptin and FABP4 concentrations, 81 and 45% variance were explained by SAT mass, VAT mass, and gene expression in SAT in multivariable regression models. For the remaining adipokines, AT mass and gene expression explained <16% variance of plasma concentrations. Gene expression in SAT was a less important predictor compared to AT mass. SAT mass was a better predictor than VAT mass for leptin (partial correlation r = 0.81, 95% confidence interval 0.75–0.86, vs. r = 0.58, 95% confidence interval 0.46–0.67), while differences between AT compartments were small for the other adipokines. Conclusions: While plasma levels of leptin and FABP4 can be explained in a large and medium part by the amount of AT and SAT gene expression, surprisingly, these predictors explained only little variance for all other investigated adipokines.

The sex specific effect of alcohol consumption on circulating levels of CTRP3.

The goal of this project was to establish the effect of alcohol consumption on the circulating levels of the adipose tissue derived protein C1q TNF Related Protein 3 (CTRP3). Adipose tissue secretes several adipokines, such as adiponectin and leptin, which exert a multitude of biological effects important for human health. However, adipose tissue is extremely sensitive to alcohol consumption, leading not only to disrupted fat storage, but also to disruptions in adipokine production. Changes to adipokine secretion could have widespread biological effects and potentially contribute to alcohol-induced ailments, such as alcoholic fatty liver disease (ALD). CTRP3 has been previously demonstrated to attenuate fatty liver disease, and suppression of CTRP3 with alcohol consumption could contribute to development of and progression to alcoholic fatty liver disease. To examine the effect of ethanol consumption on circulating adipokine levels, male and female mice were fed an ethanol containing diet (Lieber-DeCarli 5% (v/v) ethanol diet) for 10-days followed by a single gavage of 5 g/kg ethanol (the NIAAA model), or for 6-weeks with no binge added (chronic model). In female mice, adiponectin levels increased ~2-fold in both models of ethanol feeding, but in male mice increased adiponectin levels were only observed after chronic ethanol feeding. On the other hand, in female mice, circulating CTRP3 levels decreased by ~75% and ~50% in the NIAAA and chronic model, respectively, with no changes observed in the male mice in either feeding model. Leptin levels were unchanged with ethanol feeding regardless of model or sex of mice. Lastly, chronic ethanol feeding led to a significant increase in mortality (~50%) in female mice, with no difference in relative ethanol consumption. These findings indicate that ethanol consumption can dysregulate adipokine secretion, but that the effects vary by sex of animal, method of ethanol consumption, and adipokine examined. These findings also indicate that female mice are more sensitive to the chronic effects of ethanol than male mice. Notably, this is the first study to document the effects of ethanol consumption on the circulating levels of CTRP3. Understanding the impact of excessive alcohol consumption on adipokine production and secretion could identify novel mechanisms of alcohol-induced human disease. However, the mechanism responsible for the increased sensitivity remains elusive.

Prediction of circulating adipokine levels by body fat compartments and adipose tissue gene expression

Introduction Over the past years, adipose tissue (AT) has been recognized as a metabolically active tissue and a number of AT-derived circulating biomarkers called adipokines have been proposed as mediators for the association of obesity with chronic disease risk. However, the mechanisms are not yet understood and it is even unclear to what extent the amount of subcutaneous (SAT) and visceral adipose tissue (VAT) and gene expression levels in AT predict adipokine concentrations. Methods In the present study, we aimed to assess to what extent adiposity as objectively measured by the amount of SAT and VAT using magnetic resonance imaging, and gene expression levels in SAT, collected by biopsy, determine plasma adipokine concentrations. We investigated the adipokines adiponectin, leptin, soluble leptin receptor, resistin, interleukin 6 and fatty acid binding protein 4 (FABP4) in a cross-sectional analysis of 200 participants from the population-based EPIC Potsdam cohort study. Our hypothesis was that direct quantification of SAT and VAT as well as gene expression in AT can explain a substantial amount of the variance in adipokine levels, and we calculated the explained variance of plasma adipokines from multivariable regression models. In secondary analyses, we investigated additional predictors (other anthropometric measures, personal characteristics, other gene expression and plasma concentration measures) and also obtained partial correlation coefficients adjusted for age, sex, physical activity and occupational training for a more detailed assessment and comparison of the associations. Results For leptin, 81%, and for FABP4, 45% of the variance in plasma concentrations was explained by SAT and VAT mass, and gene expression in SAT. For the remaining adipokines, AT mass and gene expression explained less than 16% of their variance. Gene expression in SAT explained a smaller proportion of the variance in comparison to AT mass. Regarding the AT compartments, leptin was more strongly correlated with SAT mass (partial correlation r = 0.81, 95% CI [0.75; 0.86]) than with VAT mass (r = 0.58, 95% CI [0.46; 0.67]). For the remaining adipokines, no substantial differences in their correlation with SAT versus VAT mass were observed. The additionally investigated predictors added only little explained variance for some adipokines. Conclusions Our data suggest that except for leptin and FABP4, adiposity as objectively measured by SAT and VAT mass, and gene expression in SAT predict plasma adipokine concentrations only to a small extent. While our findings do not contradict a potential role of adipokines in disease development, the circulating concentrations of all investigated adipokines except leptin and FABP4 are unlikely to mediate the association between adiposity and disease risk observed in epidemiological studies to a large extent.

Associations of circulating adipokine levels with metabolic risk factors and renal function in a general population

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