Serum Adipokine Levels Research Articles

CXCL8 expression and methylation are correlated with anthropometric and metabolic parameters in childhood obesity

Childhood obesity is a global and increasing health issue. Inflammation and dysregulated adipose tissue secretion are common findings in obesity and have been related to poor metabolic function. Given that DNA methylation impacts gene expression and is responsive to environmental changes, we aimed, in addition to characterize the patients in anthropometric and biochemical terms, to determine the expression of cytokines and adipokines, assess the methylation on regulatory regions of the genes that code for these molecules, and investigate the association of the expression and gene methylation with anthropometric and biochemical parameters in childhood obesity. Obese children present dyslipidemia, dysregulated serum levels of adipokines and their ratios, altered leukocytic expression of cytokines, and higher methylation at the CXCL8 promoter as compared to the control group. However, no significant results were observed in the fasting plasma glucose levels or the methylation of TGFB1, LEP, and the enhancer region of ADIPOQ. We also found negative correlations of CXCL8 expression with anthropometric and biochemical parameters, and positive correlation of CXCL8 promoter methylation and the serum levels of hepatic enzymes. Our results indicate that changes in metabolic parameters observed in childhood obesity are associated with the expression of adipokines and cytokines, and the methylation status at the CXCL8 promoter. CXCL8 may be a key factor for these alterations, as it correlates with many of the parameters assessed in the present study.

Metabolic syndrome and adipokine levels in systemic lupus erythematosus and systemic sclerosis

IntroductionAims of study were to evaluate the prevalence of metabolic syndrome (MetS) in systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) patients and to evaluate serum level of adipokines in SLE and SSc patients with and without MetS.MethodsFifty SLE patients and 85 SSc patients were enrolled. The diagnosis of MetS was made according to the criteria of the National Cholesterol Education Program (NCEP) Adult Treatment Panel III. Clinical assessment and serum levels of adiponectin and resistin were evaluate in SLE and SSc patients.ResultsPrevalence of MetS was significantly (p<0.0001) higher in SLE patients than SSc patients (36% vs 10.6%). Median values of resistin were significantly (p<0.001) higher in SLE patients with MetS than SLE patients without MetS [4.01 ng/mL (2.7–4.5) vs 1.92 ng/mL (1.2–3)]. Median values of adiponectin were significantly (p<0.05) lower in SLE patients with MetS than SLE patients without MetS [5.64 ng/mL (4.96–8) vs 8.38 ng/mL (6.54–11.01)]. Systemic Lupus Erythematosus Activity Index [8 (6–12) vs 10 (6–13), p<0.01] and Systemic Damage Index [2 (1–3) vs 2 (0–3), p<0.001] were significantly higher in MetS patients than in patients without MetS.In SSc, the median value of disease severity scale was significantly higher (p<0.05) in MetS patients than in patients without MetS [7 (5–7) vs 5 (3–6)].ConclusionPrevalence of MetS is higher in SLE patients. In SLE patients, MetS showed an association with adipokine levels and inflammation/activity disease scores. In SSc patients, MetS was associated with severity of disease.Key Points• Prevalence of metabolic syndrome is higher in SLE patients than SSc patients.• Resistin is higher in SLE patients with metabolic syndrome.• Adineponectin is lower in SLE patients with metabolic syndrome.• Disease severity scale is higher in SSc patients with metabolic syndrome.

ALTERATIONS IN ANTHROPOMETRIC, PHYSIOLOGICAL AND BIOCHEMICAL PARAMETERS DURING A COMPLEX EXERCISE AND DIETARY TREATMENT PROGRAM FOR OBESE PATIENTS WITH CONTROLLED HYPERTENSION

Objective: Obesity and hypertension are considered as major risk factors of for cardiovascular diseases. Besides unfavorable metabolic processes, altered levels of pro-inflammatory factors and adipokines produced by the white adipose tissue have various role in atherogenesis. In our study, we aimed to investigate the impact of exercise and dietary therapies on these unfavorable processes in obese, controlled hypertensive patients. Design and method: Forty-two obese subjects with controlled hypertension were enrolled in our six-week self-controlled clinical trial. The load capacity was assessed by ergospirometry and the maximum VO2 uptake (VO2max), respiratory anaerobic threshold (V-slope) and maximum metabolic equivalent (MET) were determined. Body composition analysis and six- minute walking test (6MWT) were also performed. We also investigated serum lipid parameters, high-sensitivity C-reactive protein (hsCRP) levels, oxidized low-density lipoprotein (oxLDL) concentrations, paraoxonase (PON1) activities and calculated the homeostatic model assessment (HOMA)-insulin resistance (HOMA-IR). Serum adipokine levels including leptin, adiponectin, tumor necrosis factor (TNF)-alfa, chemerin, resistin, lipocalin-2 concentrations were also measured. All of our tests were repeated at the end of the six-week program, during which, the patients received 3 x 50 minutes of exercise training. Dietotherapy was also provided twice a week. Results: Each patient completed the program (age: 58.12 ± 10.4 years, M/F: 9/33, initial mean body mass index /BMI/: 44.24 ± 7.22 kg/m2, mean blood pressure /BP/: 132,21 ± 5,74 mmHg). At the end of the program, BMI and BP were significantly reduced (p &lt; 0.00001, p &lt; 0.01, respectively), with improvement in all functional tests (p &lt; 0.0001), VO2max (p &lt; 0.000002) and in V-slope (p = 0.001). LDL-cholesterol and oxLDL concentrations decreased significantly (p = 0.0005, p = 0.0009, respectively), while high-density lipoprotein (HDL)-cholesterol levels showed a significant increase (p = 0.0028). HOMA-IR also improved significantly (p = 0.006) and the percentage of body fat mass was reduced significantly (p = 0.000036). Among the adipokines, only the circulating concentrations of lipocalin-2 and leptin were significantly decreased (p = 0.036, p &lt; 0.000001, respectively). HsCRP concentration and PON activity were also found to be significantly reduced (p &lt; 0.00001, p = 0.0032, respectively). Conclusions: Besides its beneficial physiological effects, an aerobic exercise program combined with dietotherapy improves pro-atherogenic, pro-inflammatory and metabolic factors in obese patients with controlled hypertension.

The Effect of FGF21 and Its Genetic Variants on Food and Drug Cravings, Adipokines and Metabolic Traits.

Fibroblast growth factor 21 (FGF21) is a regulator of addictive behavior. Increasing evidence suggests an impact of FGF21 on eating behavior, food and drug cravings and on other adipokines like insulin-like growth factor 1 (IGF-1) or adiponectin. We investigated the association of serum FGF21 and genetic variants with aspects of food and drug craving and obesity related metabolic parameters including serum adipokine levels. Standardized questionnaires, blood samples and anthropometric data of the Sorbs cohort (n = 1046) were analyzed using SPSS. For genetic analyses, the FGF21-locus ±10 kb was genotyped and analyzed using PLINK. Validation was conducted in a second independent cohort (n = 704). FGF21 was significantly associated with alcohol and coffee consumption, smoking and eating behavior (disinhibition). We confirmed correlations of FGF21 serum levels with IGF-1, adiponectin, pro-enkephalin, adipocyte fatty-acid-binding protein, chemerin and progranulin. FGF21 genetic variants were associated with anthropometric and metabolic parameters, adipokines, food and drug craving while strongest evidence was seen with low-density lipoprotein cholesterol (LDL-C). We highlight the potential role of FGF21 in food and drug cravings and provide new insights regarding the link of FGF21 with other adipokines as well as with metabolic traits, in particular those related to lipid metabolism (LDL-C).

Effects of increased physical activity and/or weight loss diet on serum myokine and adipokine levels in overweight adults with impaired glucose metabolism.

The purpose of this study was to investigate the changes in serum irisin, fibroblast growth factor-21 (FGF21), visfatin, follistatin like protein-1 (FSTL1), and meteorin-like protein (Metrnl) levels in response to increased physical activity and/or diet interventions in overweight subjects with impaired glucose metabolism (IGM). A total of 60 subjects (BMI > 25.0 kg/m2) with IGM were recruited in this single-centered interventional study. Twelve subjects dropped out during the study and the study was completed with 48 patients. Patients were divided into two groups as diet only (DI, n = 24) and diet and physical activity intervention (DPA, n = 24). Patients in DI group received a diet program while DPA group received a diet combined with a physical activity intervention for 12 weeks. Additional 24 healthy subjects were recruited to compare the baseline levels of proteins. Serum protein levels, anthropometric measurements, and biochemical parameters were assessed. Irisin, FGF21, visfatin, and FSTL1 levels significantly decreased in both groups after 12-week intervention (p < 0.001). However, there were no differences in protein levels between DI and DPA groups (p > 0.05). Likewise, the total change in weight was similar in both DI (-4.35 kg) and DPA (-4.85 kg) groups (p > 0.05). A 5% reduction in initial body weight with DPA therapy resulted in a stronger correlation between the changes in irisin, visfatin, and FSTL1 levels and fasting glucose and HbA1c levels. These results demonstrate that serum irisin, FGF21, visfatin, and FSTL1 levels decreased in response to weight loss interventions. Weight loss induced by DI or DPA therapies had similar lowering effects on these proteins in subjects with IGM, and these myokines might be related to glucose metabolism biomarkers.

C1q/TNF-Related Protein 3 (CTRP-3) Deficiency of Adipocytes Affects White Adipose Tissue Mass but Not Systemic CTRP-3 Concentrations

CTRP-3 (C1q/TNF-related protein-3) is an adipokine with endocrine and immunological function. The impact of adipocyte CTRP-3 production on systemic CTRP-3 concentrations and on adipocyte biology is unknown. A murine model of adipocyte CTRP-3 knockout (KO) was established (via the Cre/loxP system). Serum adipokine levels were quantified by ELISA and adipose tissue (AT) gene expression by real-time PCR. Preadipocytes were isolated from AT and differentiated into adipocytes. Comparative transcriptome analysis was applied in adipocytes and liver tissue. Body weight and AT mass were reduced in CTRP-3 KO mice together with decreased serum leptin. In primary cells from visceral AT of KO mice, expression of adiponectin, progranulin, and resistin was induced, while peroxisome proliferator activated receptor γ (PPARγ) was decreased. M1/M2 macrophage polarization markers were shifted to a more anti-inflammatory phenotype. CTRP-3 expression in AT did not contribute to serum concentrations. AT and liver morphology remained unaffected by CTRP-3 KO. Myelin transcription factor 1-like (Myt1l) was identified as a highly upregulated gene. In conclusion, adipocyte CTRP-3 has a role in adipogenesis and AT weight gain whereas adipocyte differentiation is not impaired by CTRP-3 deficiency. Since no effects on circulating CTRP-3 levels were observed, the impact of adipocyte CTRP-3 KO is limited to adipose tissue. Modified AT gene expression indicates a rather anti-inflammatory phenotype.

Zinc Supplementation Might Not Affect Serum Leptin and Adiponectin Levels in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials.

Background:Zinc as one of the important trace elements in human health has been suggested to be a supplement for modifying the level of adipokines, whereas findings from studies have been inconsistent. This study aimed to systematically review the evidence provided by randomized controlled trials (RCTs) regarding the effect of zinc supplementation on serum adipokines levels.Methods:PubMed, Google Scholar, Web of Science, and Scopus were systematically searched up to June 2019. The mean differences and their corresponding standard deviations (SDs) of changes in serum adipokines levels were used as effect size.Results:Eight eligible RCTs (leptin n=6, adiponectin n=3) were included in the current study. There were no significant changes in serum leptin levels [weighted mean difference (WMD) =0.60 ng/ml, 95% confidence interval (CI): −1.78, 2.99; I-squared (I2) = 64.3%] and adiponectin levels (WMD = 1.09 ng/ml, 95% CI: −0.76, 3.18, I2 = 78.8%) following zinc supplementation compared to placebo group. These findings did not change after considering several subgroups including gender, study duration, health status, body weight and the type of zinc used for supplementation.Conclusion:No evidence was found to support the efficacy of dietary zinc supplements on serum levels of adipokines. Further, high-quality, long-term controlled clinical trials are warranted to confirm these findings.

Inflammatory and Adipokine Status from Early to Midpregnancy in Arab Women and Its Associations with Gestational Diabetes Mellitus.

Objective To examine differences in maternal serum levels of adipokines (adiponectin, leptin, and resistin) and inflammatory markers (tumor necrosis factor-alpha (TNF-α) and interlukin-6 (IL-6)) from early to midpregnancy among Arab women with or without gestational diabetes mellitus (GDM), along with their links to GDM risk. Methods This is a multicenter prospective study involving 232 Saudi women attending obstetric care. Both circulating adipokine and markers of inflammation were observed at the first (eight to 12 weeks) and second trimesters (24 to 28 weeks). GDM was screened at 24 to 28 weeks using the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria. Results Age and body mass index- (BMI-) matched circulating TNF-α was significantly higher in women with GDM in comparison to non-GDM women (p = 0.01). Adiponectin and resistin significantly decreased from the first to second trimester in women without GDM (p = 0.002 and 0.026, respectively). Leptin presented a significant rise from the first to second trimester in both groups, with a higher increase in women with GDM (p = 0.013). Multivariate logistic regression analysis revealed that TNF-α was significantly correlated with GDM (p = 0.03). However, significance was lost after adjustments for maternal and lifestyle risk factors (OR 23.58 (0.50 to 1119.98), p = 0.11). Conclusion Inflammatory and adipocytokine profiles are altered in Arab women with GDM, TNF-α in particular. Further studies are needed to establish whether maternal inflammatory and adipocytokine profile influence fetal levels in the same manner.

Molecular basis of non-alcoholic fatty liver disease and metabolic syndrome in a subset of South Asians

Metabolic syndrome (MetS) and non-alcoholic fatty liver disease (NAFLD) are emerging threats in Pakistan. The prevalence of MetS is reported to be 18–46% in general population. Adipokines and their genetic polymorphisms are now considered as risk factors for these conditions. Chemerin modulates glucose and lipid homeostasis, nesfatin-1 acts as an anorexigenic peptide, desnutrin regulates adipose tissue fatty acid oxidation, adipocyte fat content, and size. Therefore, this study was designed to identify the molecular and genetic differences in the above-mentioned biomarkers in metabolic syndrome positive and negative individuals. This cross-sectional study was carried out at the Aga Khan University during October 2018 till August 2019. MetS positive (n = 92) versus negative (n = 208) adults aged between 18 and 50 years of age were recruited. MetS was diagnosed on the basis of National Cholesterol Education Program Adult Control Panel III criteria. Serum adipokine levels, lipid profile, blood glucose, and insulin were measured. Fatty liver was detected by ultra-sonographic scans. Chemerin rs17173608 polymorphism was determined by tetra-arm polymerase chain reaction. Higher chemerin (37.87 ± 13.60 vs. 24.03 ± 12.32 pg/ml), low desnutrin (103.08 ± 5.84;270.19 ± 25.67 pg/ml), and nesfatin levels (276.49 ± 31.09; 754.34 ± 57.77 pg/ml) were seen in Mets/NAFLD positive versus negative individuals, respectively. Serum chemerin showed a moderate positive correlation with MetS and fatty liver while desnutrin showed weak correlation with MetS, whereas nesfatin showed a moderate correlation with MetS and fatty liver (p < 0.05). Each unit increases in chemerin, and decrease in desnutrin was associated with higher odds of developing NAFLD (p < 0.05). The variant rs17173608 showed association with MetS phenotype (1.841 (1.101–3.078); p = 0.020). Presence of the minor “G” allele was seen to increase the risk of developing MetS by 1.567 (p < 0.012). High chemerin and low desnutrin are linked to fatty liver changes and MetS in a subset of local population. The presence of chemerin “G” allele increases the risk of developing MetS even further in the same individuals. Further studies are required for an in-depth analysis of the mechanism through which these biomarkers cause the effect.

Effect of One Course Pilates Exercise Program on Serum Levels of Resistin, Visfatin, and Chemerin in Overweight Women

Aims: Hemostasis and serum levels of adipokines in the body are affected by physical activity and overweight. The present study investigates the effect of the Pilates exercise program on serum levels of resistin, visfatin, and chemerin in overweight women Methods &amp; Materials: In this quasi-experimental study, 28 women with overweight voluntarily participated and were randomly divided into two groups of exercise (n=14) and control (n=14). The Pilates exercise program was presented to the exercise group for 8 weeks, 3 sessions per week, while the control group performed no exercise. Blood samples were taken before the intervention and 48 hours after the intervention in a fasting state to measure the serum levels of resistin, visfatin, and chemerin. The t-test was used for intra-group comparison and ANCOVA for inter-group comparison of the variables. The obtained data were analyzed in SPSS v. 23, considering a significance level of P&lt;0.05 Findings: After 8 weeks of Pilates exercise, serum levels of resistin (P=0.001), visfatin (P=0.045), and chemerin (P=0.009) decreased significantly compared to pre-test values. A significant reduction in serum levels of resistin (P=0.005), visfatin (P=0.034), and chemerin (P=0.025) were also reported compared to the control group Conclusion: It seems that Pilates exercise can reduce resistin, visfatin, and chemerin levels in overweight women and can be considered as an appropriate exercise program to control the health and physiological conditions of overweight women

Association of adipokines with frailty in heart failure.

BackgroundFrailty is a multifactorial physiological syndrome most often associated with age but which has received increasing recognition as a component of chronic illnesses such as heart failure. Patients with heart failure are likely to be frail, irrespective of their age. Adipokine dysregulation, which is associated with frailty, occurs in patients with heart failure. In this study, we tested the hypothesis that adipokines are associated with skeletal muscle and bone mineral density that change lead to frailty in patients with heart failure.MethodsThirty-five patients with heart failure (age, 67 ± 14 years; 25 males; left ventricular ejection fraction, 45 ± 19%) were included. Serum adipokine levels, physical performance, and body composition were measured.ResultsAdiponectin and leptin were inversely correlated with grip strength. Adiponectin was inversely correlated with bone mineral density. Leptin was positively correlated with fat mass. Adipokines were not correlated with skeletal muscle mass.ConclusionsAdipokines were associated with grip strength and bone mineral density in patients with heart failure. Adipokine dysregulation may play a role in the development of frailty in heart failure.

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.

Adipokines in the Skin and in Dermatological Diseases.

Adipokines are the primary mediators of adipose tissue-induced and regulated systemic inflammatory diseases; however, recent findings revealed that serum levels of various adipokines correlate also with the onset and the severity of dermatological diseases. Importantly, further data confirmed that the skin serves not only as a target for adipokine signaling, but may serve as a source too. In this review, we aim to provide a complex overview on how adipokines may integrate into the (patho) physiological conditions of the skin by introducing the cell types, such as keratinocytes, fibroblasts, and sebocytes, which are known to produce adipokines as well as the signals that target them. Moreover, we discuss data from in vivo and in vitro murine and human studies as well as genetic data on how adipokines may contribute to various aspects of the homeostasis of the skin, e.g., melanogenesis, hair growth, or wound healing, just as to the pathogenesis of dermatological diseases such as psoriasis, atopic dermatitis, acne, rosacea, and melanoma.

The role of chemerin in the pathogenesis of cholelithiasis in children and adolescents.

Adipokines and hepatokines are proteins secreted by adipose tissue and the liver. To date, the levels of adipokines and hepatokines in cholelithiasis have only been evaluated in studies in adult patients. The purpose of our research was to assess the levels of circulating adipokines: chemerin, vaspin, progranulin, retinol-binding protein 4 (RBP-4) and hepatokine: fibroblast growth factor 21 (FGF-21) and to compare their concentrations in paediatric patients with and without cholelithiasis. The prospective study included 54 children and adolescents diagnosed with gallstones and 26 controls. Fasting serum levels of adipokines and hepatokine were determined by enzyme-linked immunosorbent assays. The serum levels of chemerin, FGF-21 and RBP-4 were significantly higher in children and adolescents with gallstones compared to the control group. Elevated levels of triglycerides, RBP-4, and a homeostatic model for assessing insulin resistance (HOMA-IR) were observed in overweight or obese patients compared to patients with normal weight and cholelithiasis. Chemerin concentrations were increased in the normal-weight children and adolescents with cholelithiasis compared to the control group. Children and adolescents with gallstones and abnormal weight had significantly higher levels of chemerin, FGF-21 and RBP-4 than healthy controls. Elevated serum chemerin levels were significantly higher in non-obese patients with cholelithiasis than in non-obese controls, suggesting a potential role of chemerin in the development of cholelithiasis in children and adolescents.

Bariatric surgery-induced weight loss reduces B cell activating cytokines and IgG immunoglobulins related to autoimmunity.

Obesity is associated with a chronic inflammatory state and autoimmune diseases, but little is known about the role of B cells in this context and the changes in B cell activation factors during obesity and after weight loss. To test whether bariatric-surgery-induced weight loss ameliorates the systemic inflammatory state associated with B cell activation molecules. We conducted a prospective observational study in patients treated with bariatric surgery. Anthropometric and body composition measurements were performed preoperatively and at 6months of follow-up post surgery. The patients were tested for a biochemical profile, plasmatic immunoglobulin G (IgG), cytokines (including specific B cell activating cytokines), and adipokines serum levels RESULTS: The patients' weight loss was accounted for mostly by fat mass (52.9%). We observed a significant reduction in total plasmatic IgG levels (p = 0.001), which could be associated with decreased B cell activity. Accordingly, there was a significant decrease in the B cell activating factors such as APRIL, BAFF, and soluble CD40L and a general improvement in the inflammatory markers hs-CRP, IL-1β, IL-12, IL-18, and IFN-γ. These findings point toward reduced B cell activity after weight loss due to bariatric surgery. Moreover, they could be the initial link among the systemic inflammatory factors, and B cell activation in this inflammatory context that leads to IgG production and, potentially, to autoimmunity in patients with severe obesity.

Fenugreek attenuates obesity-induced inflammation and improves insulin resistance through downregulation of iRhom2/TACE

AimsWe previously reported that fenugreek-derived 4-hydroxyisoleucine ameliorates insulin resistance via regulation of TNF-α converting enzyme (TACE) expression. In the present study, we further investigate the effects and mechanisms of fenugreek on obesity-induced inflammation and insulin signaling in the high-fat diet (HFD)-challenged obese mice. Main methodsAfter 12 weeks of HFD intervention, mice were treated with the low or high dosages of fenugreek. Serum levels of glucose, insulin, lipid profile, inflammation cytokines, and adipokines were detected. Macrophage infiltration and adipose tissue morphology were observed. Western blot was conducted to investigate the expressions of inactive rhomboid 2 (iRhom2) and TACE as well as other signaling pathways in subcutaneous adipose tissue. Key findingsWe showed that fenugreek significantly suppressed body weight gain and fat accumulation in HFD-challenged obese mice. Meanwhile, fasting glucose, insulin, and HOMA-IR in fenugreek-treated mice were remarkably decreased, which were properly explained by fenugreek-induced activation of the insulin receptor signaling pathway. Moreover, the anti-inflammatory properties of fenugreek were shown by the decrease of systemic and local expressions of pro-inflammatory cytokines as well as reduced macrophage infiltration into adipose tissue. Additionally, fenugreek markedly deactivated NF-κB and JNK pathways. Finally, we demonstrated that fenugreek strikingly repressed the transcriptions and expressions of iRhom2 and TACE. SignificanceFenugreek shows an encouraging and promising property in ameliorating insulin resistance and suppressing inflammation in obesity, which might be realized by fenugreek-mediated inhibition of iRhom2/TACE axis-facilitated TNF-α release from adipocytes.

Adipokines and periodontal markers as risk indicators of early rheumatoid arthritis: a cross-sectional study.

To establish the association between adipokine levels and markers of periodontal involvement as risk indicators of early stages of RA (eRA) and the interaction between the presence of markers of periodontal disease with adipokine in eRA individuals. Fifty-one patients with a diagnosis of eRA and 51 healthy controls matched for age and sex were studied. Clinical joint condition, clinical and serological markers of disease activity, serum adipokine levels (leptin, adiponectin, resistin, adipsin, vaspin, and IL-6), periodontal diagnosis, presence of Porphyromonas gingivalis, and related IgG1 and IgG2 antibodies were evaluated. Comparisons were made between eRA and healthy controls for periodontal indicators and adipokines. A subgroup analysis was realized with a non-conditional logistic regression to establish the association between the levels of leptin in individuals with eRA and controls according to the periodontal condition, presence of P. gingivalis, or high titers of IgG antibodies against P. gingivalis. The condition of overweight or obesity is associated with the diagnosis of eRA (p = 0.05), and these individuals also have higher levels of leptin (p = 0.001) and vaspin (p = 0.007). Higher frequency of P. gingivalis (p = 0.001) was found in the eRa group. Individuals with eRA with higher IgG2 titers against P. gingivalis had higher levels of leptin (OR: 1.66 (CI 95% 1.01-2.73)); however, individuals with periodontitis or P. gingivalis with eRA were associated with highest levels of leptin (OR: 1.86, CI 95% 1.19-24.3; and OR: 2.04, CI 95% 1.37-3 respectively). eRA individuals have high levels of leptin and vaspin. However, the presence of periodontitis and related-periodontal disease markers showed an effect only in leptin levels in eRA individuals. Emphasizing in personalized medicine, monitoring serum leptin levels and periodontitis markers can improve the early diagnosis of RA.

A potential role of fatty acid binding protein 4 in the pathophysiology of autism spectrum disorder.

Autism spectrum disorder is a neurodevelopmental disorder characterized by difficulties in social communication and interaction, as well as repetitive and characteristic patterns of behaviour. Although the pathogenesis of autism spectrum disorder is unknown, being overweight or obesity during infancy and low weight at birth are known as risks, suggesting a metabolic aspect. In this study, we investigated adipose tissue development as a pathophysiological factor of autism spectrum disorder by examining the serum levels of adipokines and other metabolic markers in autism spectrum disorder children (n = 123) and typically developing children (n = 92) at 4–12 years of age. Among multiple measures exhibiting age-dependent trajectories, the leptin levels displayed different trajectory patterns between autism spectrum disorder and typically developing children, supporting an adipose tissue-dependent mechanism of autism spectrum disorder. Of particular interest, the levels of fatty acid binding protein 4 (FABP4) were significantly lower in autism spectrum disorder children than in typically developing subjects, at preschool age (4–6 years old: n = 21 for autism spectrum disorder and n = 26 for typically developing). The receiver operating characteristic curve analysis discriminated autism spectrum disorder children from typically developing children with a sensitivity of 94.4% and a specificity of 75.0%. We re-sequenced the exons of the FABP4 gene in a Japanese cohort comprising 659 autism spectrum disorder and 1000 control samples, and identified two rare functional variants in the autism spectrum disorder group. The Trp98Stop, one of the two variants, was transmitted to the proband from his mother with a history of depression. The disruption of the Fabp4 gene in mice evoked autism spectrum disorder-like behavioural phenotypes and increased spine density on apical dendrites of pyramidal neurons, which has been observed in the postmortem brains of autism spectrum disorder subjects. The Fabp4 knockout mice had an altered fatty acid composition in the cortex. Collectively, these results suggest that an ‘adipo-brain axis’ may underlie the pathophysiology of autism spectrum disorder, with FABP4 as a potential molecule for use as a biomarker.

Insulin resistance and serum levels of adipokines in patients with systemic lupus erythematosus: a systematic review and meta-analysis

We aimed to perform a systematic review and meta-analysis of studies assessing the homeostasis model assessment for insulin resistance (HOMA-IR) values, serum adiponectin, leptin and resistin levels in patients with systemic lupus erythematosus (SLE). Online databases were searched on 31 March 2019 in order to identify studies comparing HOMA-IR, serum adiponectin, leptin and resistin levels between patients with SLE and controls. A random-effects model was adopted. Fifty-six studies involving a total of 4460 patients with SLE were included. Patients with SLE had significantly higher HOMA-IR values (standardized mean difference (SMD)=0.425; 95% confidence interval (CI) 0.156-0.693; I2=93.8%) than the control group. The serum levels of adiponectin (SMD=0.547; 95% CI 0.219-0.874; I2=90.1%), leptin (SMD=0.843; 95% CI 0.454-1.231; I2=94.4%) and resistin (SMD=0.856; 95% CI 0.199-1.513; I2=96.6%) were all higher among patients with SLE than controls. A meta-regression analysis revealed that the serum resistin level was positively correlated with disease activity (coefficient 0.123; 95% CI 0.051-0.195; p<0.001). Patients with SLE have higher HOMA-IR values and serum levels of adiponectin, leptin and resistin than individuals without SLE. The serum level of resistin correlates with SLE disease activity.

The association between the route of nutrition and serum levels of adipokines in critical illness: a pilot study

Background/aimAdipokines play an important role in the regulation of metabolism. In critical illness, they alter serum levels and are suspected to worsen clinical outcomes. But the effect of the route of nutrition on adipokines is not known. The purpose of this study was to evaluate the association between the route of nutrition and adipokine levels in critically ill patients.Materials and methodsThis prospective study was performed in an intensive care unit (ICU). Patients admitted to the ICU for least 72 h and receiving either enteral nutrition (EN) via tube feeding or parenteral nutrition (PN) were enrolled. Serum was obtained at baseline, 24 h, and 72 h for concentrations of leptin, adiponectin, resistin, glucagon–like peptide 1 (GLP–1), insulin–like growth factors 1 (IGF–1), and ghrelin.Results A total of 26 patients were included in the study. Thirteen patients received EN and 13 patients received PN. In the PN group, leptin level significantly increased (P = 0.037), adiponectin and ghrelin significantly decreased during follow up (P = 0.037, P = 0.008, respectively). There was no significant change between all adipokines in the EN group and resistin, IGF–1 and GLP–1 in the PN group during follow up. Resistin levels were markedly lower in the EN group at both 24 h (P = 0.015) and 72 h (P = 0.006) while GLP–1 levels were higher in the EN group at baseline, 24 h, and 72 h (P = 0.018, P = 0.005, and P = 0.003, respectively). There were no differences in leptin, adiponectin, IGF–1, and ghrelin levels over time. ConclusionThe delivery of EN in critical illness was associated with decreased resistin levels and increased GLP–1 levels. Thus, the route of nutrition may impact the clinical outcome in critical illness due to adipokines.