Adipocytokine Levels Research Articles

Serum Levels of Asprosin, a Novel Adipokine, Are Significantly Lowered in Patients with Acromegaly.

Background Asprosin is a novel identified adipokine secreted mainly by white adipose tissue, which is elevated in metabolic diseases such as diabetes and obesity. Acromegaly is a syndrome caused by pituitary growth hormone (GH) cell adenoma with excessive GH secretion. Serum adipocytokines levels may be involved in abnormal glycolipid metabolism in acromegaly patients. Objectives To investigate serum asprosin levels in acromegaly patients and its correlation with high GH levels and glucolipid metabolic parameters. Methods A retrospective case-control study was conducted and 68 acromegaly patients and 121 controls were included in this study. Clinical information and laboratory examinations were collected and serum asprosin levels were measured by commercial ELISA kits. Results Serum asprosin levels in acromegaly patients were significantly lower than controls (P < 0.001). Serum asprosin levels in patients with the course of acromegaly ≥5 years (compared with <5 years), high area under curve of growth hormone (GH-AUC) after 75 g oral glucose tolerance test (OGTT) (compared with low GH-AUC patients), and high IGF-1 SDS group (compared with low IGF-1 SDS group) were significantly reduced (all P < 0.05). Serum asprosin levels in acromegaly patients were negatively correlated with the course of acromegaly, IGF-1 SDS, nadir growth hormone value (GH-Nadir), and GH-AUC after OGTT. Multiple stepwise linear regression indicated that acromegaly was an independent influencing factor of serum asprosin levels. According to serum asprosin levels tertiles, the risk of acromegaly in the lowest group was 2.67 times higher than the highest group (OR ＝ 3.665, 95% CI 1.677 ∼ 8.007, P=0.001), and the increased risk of the lowest group still existed after adjusting for gender, age, BMI, and TC (Model 2). Conclusions Serum asprosin levels in acromegaly patients are lowered, which may be related to increased blood glucose and reduced body fat mass caused by long-term high GH levels exposure.

Impact of malnutrition on systemic immune and metabolic profiles in type 2 diabetes

BackgroundWhile obesity and overweight status are firmly established risk factors for Type 2 diabetes mellitus (T2DM), a substantial proportion of diabetic individuals, especially in Africa and Asia, are often underweight or normal weight. However, very little is known about the immunological and metabolic profiles of these individuals.MethodsThis study aimed to assess the relationship between malnutrition and Type 2 diabetes mellitus (T2DM). We examined a variety of analytes associated with the immunological and metabolic profiles of T2DM individuals with low (< 18.5 kg/m2) or normal (18.5–24.9 kg/m2) body mass index (BMI). To this end, we measured plasma levels of HbA1c, glucose, insulin, glucagon, adipocytokines and Type 1, Type 2, Type 17, pro-inflammatory and regulatory cytokines in T2DM individuals with low BMI (LBMI) or normal BMI (NBMI) with small sample size n = 44 in each group.ResultsLBMI individuals exhibited significantly higher levels of HbA1c, random blood glucose, insulin and glucagon compared to NBMI individuals. Similarly, LBMI individuals exhibited significantly higher levels of adiponectin and adipsin and significantly lower levels of leptin in comparison to NBMI individuals. LBMI individuals also exhibited significantly lower levels of the Type 1, Type 2, Type 17, pro-inflammatory and regulatory cytokines in comparison to NBMI individuals. Finally, while the metabolic parameters exhibited a significant negative correlation with BMI, the immunological parameters exhibited a significant positive correlation with BMI.ConclusionsMalnutrition is associated with a significant modulation of glycemic, hormonal and cytokine parameters in T2DM. Hence, the biochemical and immunological profiles of T2DM is significantly influenced by BMI.

Association of adipocytokines serum levels with left atrial thrombus formation in atrial fibrillation patients on oral anticoagulation (Alert) – A cross-sectional study

Background and aimsOral anticoagulation is effective for stroke prevention in atrial fibrillation (AF). However, strokes may still occur in high-risk individuals. We conducted a prospective trial to assess the association between adipocytokine serum levels and surrogate parameters for thromboembolic events. Methods and resultsIn this cross-sectional multicenter trial, we enrolled 189 patients with AF who were on oral anticoagulation. The primary endpoint was defined as either the presence of spontaneous echo contrast (SEC), a left atrial appendage (LAA), or a left atrial (LA) thrombus on transesophageal echocardiography. We investigated the association of adipocytokine serum levels with the combined endpoint using logistic regression analysis. Forty-eight individuals (25%) were assigned to group 1 (G1) due to the occurrence of at least one of the components of the combined endpoint (41 [21.7%] SEC, 3 [1.6%] LA thrombus, 13 [6.9%] LAA thrombus), whereas the remaining patients formed group 2 (G2). The BMI, logarithmized (loge) leptin (G1: 2.0 ± 1.3 μg/ml, G2: 2.0 ± 1.1 μg/ml, p = 0.746) and visfatin serum levels (G1: 3.4 ± 0.3 ng/ml, G2: 3.4 ± 0.5 ng/ml, p = 0.900) did not significantly differ between the groups. Conversely, logarithmized adiponectin (G1: 3.3 ± 0.6 ng/ml, G2: 3.1 ± 0.7 ng/ml, p = 0.036) and resistin levels (G1: 1.8 ± 0.5 ng/ml, G2: 1.6 ± 0.5 ng/ml, p = 0.009) were higher in patients with the primary endpoint. Multivariate logistic regression analysis using a score that combined the individual adiponectin and resistin values in each patient corroborated this association. ConclusionsOur results suggest that adiponectin and resistin may act as potential biomarkers to identify individuals with AF who are at high thromboembolic risk.

Chronic Exposure to Environmental Level Phenanthrene Induces Non-Obesity-Dependent Insulin Resistance in Male Mice.

Epidemiological evidence shows that the body burden of polycyclic aromatic hydrocarbons (PAHs) is related to the disruption of glucose homeostasis. However, the contribution of PAHs to the development of diabetes remains poorly documented. In the current work, male Kunming mice received phenanthrene (Phe) (5, 50, and 500 ng/kg) by gavage administration once every 2 days for 28 weeks. The significant elevation of homeostasis model assessment-insulin resistance (HOMA-IR) and HOMA-β cell, accompanied by hyperinsulinemia, indicated the occurrence of insulin resistance. The suppression of the insulin receptor signaling pathway in skeletal muscle might be responsible for glucose intolerance. Under the nonobese state, the serum levels of resistin, tumor necrosis factor-α, and interleukin-6 were elevated, whereas the levels of adiponectin were reduced. These changes in adipocytokine levels were consistent with their transcription in white adipose tissue. The promoter methylation levels of Retn (encoding resistin) and Adipoq (encoding adiponectin) were inversely correlated with their mRNA levels, indicating that Phe exposure could cause the disruption of adipocytokine secretion via epigenetic modification. The results would be helpful for understanding the pathogenesis in the development of T2DM caused by nonobesogenic pollutants.

Maternal circulating levels of Adipocytokines and insulin resistance as predictors of gestational diabetes mellitus: preliminary findings of a longitudinal descriptive study.

The present study aimed to assess the role of adipocytokines as predictive markers of gestational diabetes mellitus (GDM). We undertook this study to explore the association of adiponectin, resistin, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) and insulin resistance in the development of GDM. This longitudinal descriptive study was done in the Medical College Hospital, involving the departments of Biochemistry and Gynecology. The study subjects were pregnant women with normal body mass index. They were recruited at 12-14weeks of gestation, The healthy pregnant women were selected and were followed at 24-28weeks for screening of GDM. The participants were categorized as healthy and GDM based on oral glucose tolerance test results. Blood samples were collected on both the occasions at 12-14weeks and 24-28weeks. The serum samples were analyzed for levels of insulin, adiponectin, resistin, IL-6 and TNF-alpha. Insulin resistance (HOMA-IR) was calculated from serum insulin and plasma glucose values. The levels of HOMA-IR, resistin, IL-6 and TNF-alpha were significantly higher and level of adiponectin was significantly lower in GDM subjects in comparison to healthy pregnant women, when compared both at 12weeks and 24weeks. The levels of resistin, IL-6 and TNF-alpha were significantly higher and level of adiponectin was lower at 24weeks in comparison to 12weeks, in the healthy pregnant women as well as those with GDM . Significant difference in the levels of adipocytokines between the healthy and GDM pregnant women suggest potential clinical application of these molecules as biomarkers of GDM. The increase or decrease in the levels of adipocytokines during the course of pregnancy in GDM subjects suggests their role in GDM and potential use as predictive markers.

Angiopoietin-like 8 (ANGPTL8) as a potential predictor of NAFLD in paediatric patients with Prader-Willi Syndrome

PurposeAngiopoietin-like 8 (ANGPTL8) is a liver- and adipose tissue-produced protein that predicts non-alcoholic fatty liver disease (NAFLD) and altered metabolic homeostasis in the general population as well as in persons with common and genetic obesity, including the Prader–Willi syndrome (PWS). However, its metabolic correlate in paediatric patients with respect to PWS is unknown.MethodsThis cross-sectional study investigated circulating ANGPTL8 and adipocytokines levels in 28 PWS and 28 age-, sex- and BMI-matched children and adolescents (age, 7.0–17.8y) in relation to NAFLD and metabolic homeostasis assessed by OGTT, paediatric metabolic index (PMI) and fatty liver index (FLI), liver ultrasonography (US), as well as dual-energy X-ray absorptiometry (DEXA) for analysis of fat (FM) and fat-free mass (FFM).ResultsAt the set level of significance, PWS children showed lower values of FFM (p < 0.01) but healthier insulin profiles (p < 0.01) and PMI values (p < 0.05) than matched controls. By US, the prevalence of NAFLD was similar between groups but less severe in PWS than controls. Analysis of ANGPTL8 levels showed no difference between groups, yet only in PWS ANGPTL8 levels were associated with ALT levels, FLI values and NAFLD. In stepwise multivariable regression analysis on merged data, ANGPTL8 levels were independently predicted by BMI SDS, leptin levels and NAFLD.ConclusionANGPTL8 levels are similar in PWS and controls and, overall, they are directly associated with the presence and severity of NAFLD in patients with PWS.

Maternal exposure to phenanthrene during gestation disturbs glucose homeostasis in adult mouse offspring

Epidemiological studies have indicated that polycyclic aromatic hydrocarbons were related to diabetes and insulin resistance. However, studies in mammals on the development of diabetes caused by polycyclic aromatic hydrocarbons are lacking. Pregnant mice were orally exposed to phenanthrene (0, 60 and 600 μg kg−1 body weight) once every 3 days during gestation. In adult mouse offspring, in-utero phenanthrene exposure caused glucose intolerance and decreased insulin levels in females, while caused elevated fasting blood glucose and insulin levels in males. Serum resistin and interleukin-6 levels were elevated in offspring of both sexes. Serum adiponectin levels were decreased in females but increased in males. The insulin receptor signals were upregulated in the liver and downregulated in the skeletal muscle of F1 females, while they were inhibited in both tissues of F1 males. The visceral fat weight and body weight of the treated mice were not increased, suggesting that phenanthrene is not an obesogen, which is supported by the nonsignificant alteration in pparγ transcription in visceral adipose tissue. The transcription of retn in visceral adipose tissue was upregulated in both sexes, and that of adipoq was downregulated in females but upregulated in males, which were matched with the promoter methylation levels of these genes. The results indicated that phenanthrene exposure during gestation could disturb adipocytokine levels via epigenetic modification in adult offspring, and further influence glucose metabolism. These results might be helpful for understanding nonobesogenic pollutant-induced insulin resistance and preventing against diabetes without obesity.

Characteristics of NAFLD Based on Hypopituitarism.

Background Hypopituitarism and hypothalamic disorders, which induce central obesity and appetite disorder, are associated with nonalcoholic fatty liver disease (NAFLD). We retrospectively analyzed the clinical features of NAFLD patients with hypopituitarism. Patients. We examined the cases of 15 NAFLD patients with hypopituitarism (mean age, 39.4 years; males/females, 11/4). The causes of hypopituitarism were surgical in eight cases (six with craniopharyngioma and two with prolactinoma) and nonsurgical in seven cases, including unexplained hypopituitarism in five cases, Sheehan syndrome in one case, and one case that occurred after the radiation therapy. Serum adiponectin, soluble tumor necrosis factor receptor-2 (TNFR-2), and leptin levels were measured. Results We compared the cases of the eight patients who underwent cranial surgery due to craniopharyngioma or prolactinoma and seven nonsurgical cases. The body mass index (surgery group, 30.2 ± 4.1; nonsurgery group, 29.2 ± 14.2) and the rate of diabetes (75% in surgery group, 14.3% in nonsurgery group) tended to be higher in the surgery group, and the hepatic fibrosis grade (surgery group, 3.75 ± 0.38; nonsurgery group, 1.64 ± 1.07) was significantly higher in the surgery group. The levels of adipocytokines, serum adiponectin, and serum soluble TNFR-2 showed no correlation with hepatic fibrosis, whereas the serum leptin levels were significantly correlated with liver fibrosis (R = 0.696). Conclusion The hepatic fibrosis grade rapidly progressed in the cranial surgery cases of NAFLD patients with hypopituitarism, possibly in association with BMI, diabetes mellitus, and leptin. In such cranial surgery patients, strong interventions should be considered from the early stage, including diet education, hormone replacement, and more.

Metabolically healthy obesity: prevalence, phenotype characteristic, effectiveness of weight loss

The goal was to study the prevalence of metabolically healthy obesity (MHO), the features of this phenotype compared with metabolically unhealthy obesity (MUHO), and the effect of weight loss on cardiometabolic risk factors in patients with MHO. Material and Methods — To assess the prevalence of MHO, 389 case histories of obese patients aged 18-60 were analyzed. Three types of MHO criteria were used: 1) the definitions of metabolic syndrome (MS) according to International Diabetes Federation (IDF), 2005; 2) the HOMA-IR index (&lt;2.7); 3) Biobank Standardisation and Harmonisation for Research Excellence in the European Union (BioSHaRE-EU) criteria, 2013. The study included comparative analysis of the medical history, anthropometry, basic metabolic parameters, and adipocytokine levels in 44 patients with MHO (taking into account the MS definitions) and 33 women with MUHO initially and with a decrease in body mass (BM) by ≥5% after 6 months. Results — The MHO prevalence was: according to the definitions of MS – 38.6%, according to HOMA-IR index – 34.5%, in BioSHaRE-EU – 9.6%. All indicators of anthropometry, carbohydrate and lipid metabolism, including the HOMA-IR index, interleukin-6, and chemerin, as well as the duration of obesity in the MHO and MUHO groups significantly differed (p&lt;0.05). After 6 months, MHO-patients who lost ≥5% BM from the initial value (63.6%) showed an increase of adiponectin, a decrease in waist circumference, HOMA-IR index, C-reactive protein (CRP), retinol-binding protein 4 (RBP-4), and chemerin (p&lt;0.05). Conclusion — The MHO prevalence was maximal according to the MS definitions and minimal with BioSHaRE-EU criteria. The BM decrease in MHO is accompanied by a decrease in the content of proinflammatory adipocytokines and the HOMA-IR index, which determines the need to treat obesity regardless of the phenotype.

Infrapatellar fat pads participate in thedevelopment of knee osteoarthritis in obese patients viatheactivation of the NF‑κB signaling pathway.

The aim of the present study was to assess the activation of nuclear factor‑κB (NF‑κB) in the infrapatellar fat pads (IPFPs) of obese patients with knee osteoarthritis (KOA). For this purpose, 32patients (22 obese patients with KOA and 10patients with KOA with a healthy weight) treated with total knee arthroplasty (TKA) were selected. The expression levels of pro‑inflammatory cytokines and adipocytokines, and the activation of NF‑κB were detected in both the cases and controls by enzyme‑linked immunosorbent assay (ELISA), western blot analysis and immunohistochemistry where appropriate. SPSS 18.0 software was used for statistical analysis to determine the correlation between obesity and the detected cytokine levels. It was found that in patients with KOA, the expression of leptin in the synovial fluid positively correlated with body mass index (BMI; P<0.05), and the expression of interleukin (IL)‑6 in serum significantly correlated with the IL‑1β, leptin and tumor necrosis factor (TNF)‑α levels (P<0.05). Furthermore, the expression of inflammatory cytokines and adipocytokines in IPFPs differed significantly between the obese and non‑obese patients with KOA (P<0.05). By evaluating the expression of IKKβ and IκBα and the nuclear translocation ability of p‑p65, it was concluded that NF‑κB signaling was activated to a higher degree in the IPFP tissues of obese patients with KOA than in those of patients with KOA with a healthy weight. On the whole, the findings of the present study suggested that the NF‑κB signaling pathway was activated and that there were changes in the expression in levels of inflammatory cytokines and adipocytokines in the IPFP tissues of obese patients with KOA.

Adipocytokine dysregulation, abnormal glucose metabolism, and lipodystrophy in HIV-infected adolescents receiving protease inhibitors

BackgroundLipodystrophy is common in HIV-infected patients receiving protease inhibitors (PIs), stavudine, and zidovudine. Adipocytokines may be altered in lipodystrophy. We evaluated risk factors, adipocytokine levels, insulin resistance, and lipid profiles in HIV-infected adolescents with different lipodystrophy types. MethodsA cross-sectional study was conducted in 80 perinatally HIV-infected adolescents receiving PI-based highly active antiretroviral therapy for ≥ 6 months. Patients underwent oral glucose tolerance tests and measurements of high-molecular-weight (HMW) adiponectin, leptin, resistin, insulin, and lipids. They were classified into 3 groups based on the clinical findings: no lipodystrophy, isolated lipoatrophy, and any lipohypertrophy (isolated lipohypertrophy or combined type). ResultsOf the 80 patients (median age, 16.7 years), 18 (22.5%) had isolated lipoatrophy, while 8 (10%) had any lipohypertrophy (four with isolated lipohypertrophy, and four with the combined type). In a multivariate analysis, longer exposure to stavudine (OR: 1.03; 95% CI, 1.01–1.06; p = 0.005) and indinavir (OR: 1.03; 95% CI, 1.01–1.06; p = 0.012) were associated with lipoatrophy, while longer exposure to didanosine (OR: 1.04; 95% CI, 1.01–1.08; p = 0.017) and indinavir (OR: 1.10; 95% CI, 1.00–1.21; p = 0.045) were associated with any lipohypertrophy. Leptin levels were highest in the any-lipohypertrophy group and lowest in the isolated-lipoatrophy group (p = 0.013). HMW adiponectin levels were significantly lowest in the any-lipohypertrophy group and highest in the no-lipodystrophy group (p = 0.001). There were no significant differences in the levels of resistin among the three groups (p = 0.234). The prevalence of insulin resistance (p = 0.002) and prediabetes/diabetes (p < 0.001) were significantly highest in the any-lipohypertrophy group. Patients with lipoatrophy and those without lipodystrophy had comparable degrees of insulin resistance (p = 0.292). In multiple linear regression analysis, adjusted for age, sex, and waist-height ratio, HMW adiponectin levels were associated with Matsuda index (β = 0.5; p = 0.003) and quantitative insulin sensitivity check index (QUICKI) (β = 40.1; p = 0.010) and almost significantly associated with homeostatic model assessment of insulin resistance (HOMA-IR) (p = 0.054). Leptin and resistin levels were not associated with HOMA-IR, Matsuda index, or QUICKI (all p > 0.05). ConclusionsAbnormal glucose metabolism and dysregulation of adipocytokines were common in the HIV-infected adolescents with lipohypertrophy and the combined type. Preventive screening for cardiovascular diseases caused by metabolic alterations should be routinely performed.

Weight reduction ameliorates inflammatory cytokines, adipocytokines and endothelial dysfunction biomarkers among Saudi patients with type 2 diabetes.

Type 2 diabetes mellitus (T2DM) considered as one of the cardiovascular disorders (CVD) principle risk factor as diabetes is associated with abnormal levels of endothelial function, inflammatory and adipocytokines. The aim of this study was to measure the impact of weight reducing on inflammatory cytokines, adipocytokines and endothelial function biomarkers among obese T2DM patients. One-hundred T2DM patients enrolled in the present study; the age range was 35-55 year. Participants shared in this study were enrolled in group (A) received diet control and aerobic exercise on treadmill, while, group (B) had no intervention for 3 months. The mean values of body mass index (BMI), tumor necrosis factor -alpha (TNF-α), interleukin-6 (IL-6), leptin, inter-cellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1), E-selectin and plasminogen activator inhibitor-1 activity (PAI-1 activity) were significantly decreased and adiponectin was increased significantly in the training group, however the results of the control group were not significant. Also, there were significant differences between both groups at the end of the study. Weight reducing program modulates inflammatory cytokines, adipocytokines and endothelial function biomarkers among obese T2DM patients.

Omeprazole and Spirulina Platensis Ameliorate Steatohepatitis in Experimental Nonalcoholic Fatty Liver Disease

Background: Nonalcoholic fatty liver disease (NAFLD) is a leading cause of liver damage, and it affects about 24% of the population worldwide. This study aimed to investigate the effect of omeprazole and Spirulina platensis on hepatic and serum biochemical alterations in NAFLD induced by high-fat diet (HFD). Methods: Male Wistar rats were divided into four groups; one served as a normal control. The other groups received HFD and subdivided into three subgroups; one was left untreated and the other two groups were treated orally with either omeprazole (10 mg/kg) or Spirulina (1000 mg/kg) for 30 consecutive days. Results: Omeprazole successfully decreased elevated serum pentraxin-3 (PTX-3) and cytokeratin-18 (CK-18) levels and hepatic sterol regulatory element binding protein-1c (SREBP-1c) expression, while Spirulina had better impact on decreasing liver function enzymes, lipid profile, and nuclear factor erythroid 2-related factor 2 (Nrf-2) levels compared to omeprazole. Both treatments had similar effects on normalizing glucose homeostasis, decreasing insulin resistance, and improving adipocytokine levels. Conclusion: Effects of omeprazole and Spirulina on markers of NAFLD appeared to be mediated by regulation of inflammatory, apoptotic, and oxidative mediators. Thus, omeprazole and Spirulina may find use as promising adjuvant therapy to ameliorate NAFLD. Research ethical committee of the faculty of pharmacy, Cairo University approved the research (BC 1479).

Cajanolactone A, a stilbenoid from cajanus cajan, prevents ovariectomy-induced obesity and liver steatosis in mice fed a regular diet

BackgroundVisceral obesity and fatty liver are prevalent in postmenopausal women. The stilbene-rich extract of Cajanus cajan (L.) Millsp. has been reported to prevent ovariectomy-induced and diet-induced weight gain in animal models, and stilbenoids from C. cajan are thought to have the potential to prevent postmenopausal obesity and fatty liver. PurposeCajanolactone A (CLA) is the main stilbenoid from C. cajan with osteoblastogenic promoting activity. This study investigated the potential of CLA to prevent postmenopausal obesity and fatty liver. Underlying mechanisms were also investigated. MethodOvariectomized C57BL/6 mice fed a regular diet were used as mimics of postmenopausal women and given 10, 20, or 40 mg/kg/d of CLA, 0.1 mg/kg/d of estradiol valerate (EV, positive control), or vehicle (OVX) orally for 16 weeks. Mice of the same age subjected to a sham operation were used as control (Sham). Body weights were recorded every 2 weeks for 16 weeks. Body compositions were analyzed via micro-CT. Serum levels of lipids, adipocytokines and aminotransferases were measured using the relevant kits. mRNA levels of genes of interest were detected by RT-qPCR. Proteomic study of perigonadal white adipose tissue (pWAT) was performed using tandem-mass-tags-based proteomic technology combined with Parallel-Reaction-Monitoring (PRM) validation. ResultsCLA showed potential equivalent to that of EV to prevent ovariectomy-induced overweight, obesity, dyslipidemia, liver steatosis and liver dysfunction, but did not prevent uterine atrophy. In the liver, CLA significantly inhibited ovariectomy-induced upregulation in expression of lipogenic genes SREBP-1c and ChREBP, and stimulated the mRNA expression of apolipoprotein B gene ApoB. In pWAT, CLA reversed, or partially reversed ovariectomy-induced downregulation in the expression of a number of metabolism- and mitochondrial-function-related proteins, including Ndufa3, Pcx, Pdhb, Acly, Acaca, Aldh2, Aacs and Echs1. In addition, ovariectomy-inhibited mRNA expression of Pdhb, Aacs, Acsm5, Echs1, and Aldh2 genes in pWAT was also reversed. ConclusionCLA was demonstrated to be a potential non-estrogen-like drug candidate for prevention of postmenopausal obesity and fatty liver. The underlying mechanism might involve the inhibition of lipogenesis and promotion of triglycerides output in the liver, and the promotion of metabolism and mitochondrial functions of visceral white adipose tissue.

Gender dependent differences in lipid metabolism in individuals with type 2 diabetes mellitus.

The present study investigates gender dependent effects of insulin resistance on lipid profile and adipocytokines in individuals with diabetes receiving oral antidiabetic drugs (OADs). The aim was also to reveal the changes in the expression of genes involved in lipid metabolism and inflammation. Lipid profile, adipocytokine levels and homeostatic model assessment of insulin resistance (HOMA-IR) was assessed in 100 patients with diabetes (M = 43, F = 57) matched for age and gender with healthy individuals (M = 45, F = 55). The expression pattern of genes was analyzed by quantitative real time PCR. Males consuming metformin with other drugs exhibited a positive association between HOMA-IR and cholesterol, triglyceride and very low density lipoprotein (VLDL). Females consuming only metformin and metformin with other drugs, showed a positive association of HOMA-IR with cholesterol and a negative association with adiponectin. In males and females with diabetes, a comparable expression of peroxisome proliferator activated receptor γ (PPARγ) while higher expression of sterol regulatory element binding protein 1 (SREBP1) was observed. Expression of fatty acid synthase (FAS), long chain acyl CoA Synthetases (ACSL), malonyl-CoA-acyl carrier protein transacylase (MCAT) and nuclear factor kappa β (NFkβ) was higher in men with diabetes than healthy males. Expression of tumor necrosis factor α (TNF-α) was higher in males and females with diabetes than respective healthy genders. Insulin resistance adversely affects lipid profile, adipocytokines in males with type 2 diabetes. Expression of genes involved in lipid metabolism and inflammation is found to be undesirably and differentially altered in both the genders.

Subclinical cardiovascular risk signs in adults with juvenile idiopathic arthritis in sustained remission

BackgroundJuvenile Idiopathic Arthritis (JIA) is one of the most common chronic diseases of childhood that often persists into adulthood and can result in significant long-term morbidity. As a long lasting chronic inflammatory disease, concern has been raised regarding the risk of premature development of cardiovascular disease (CVD) in JIA. This study aims to determine whether adults with JIA in clinical remission display clinical and subclinical signs of CVD risk: inflammatory mediators, adipokines, endothelial dysfunction and oxidative stress markers.MethodsThis is a cross-sectional study including 25 patients diagnosed with JIA according to the International League of Associations for Rheumatology criteria (ILAR 2001) and 25 age- and sex-matched controls. Remission was determined by JADAS10 < 1 and according to Wallace criteria. The presence of traditional CVD risk factors was analyzed. An extensive clinical analysis including body mass index (BMI), lipid profile, homeostatic model assessment – insulin resistance (HOMA-IR) and arterial blood pressure was performed. Intima media thickness of the common carotid artery (CIMT) was measured as a marker of subclinical atherosclerosis. Several proinflammatory cytokines, molecules involved in the endothelial dysfunction, oxidative stress and adipokines were quantified on serum by ELISA and on peripheral blood mononuclear cells (PBMCs) by RT-PCR. In vitro studies were carried out in healthy PBMCs, adipocytes and endothelial cells which were treated with serum from JIA patients under sustained remission.ResultsMean duration of the disease was 13.47 ± 5.47 years. Mean age was 25.11 ± 7.21. Time in remission was 3.52 ± 3.33 years. Patients were in remission with no treatment (40%) and with treatments (60%). CVD risk factors and CIMT were similar in JIA patients and controls. However, cholesterol levels were significantly elevated in JIA patients. Levels of adipocytokines, oxidative stress and endothelial activation markers were elevated in serum and PBMCs from JIA patients. Serum of those JIA patients induced the activation of adipocytes, endothelial cells and healthy PBMCs.ConclusionsJIA adult patients in remission have subclinical signs of inflammation and CVD risk, showed by an increase in the levels of inflammatory cytokines, endothelial activation and oxidative stress markers and adipokines, molecules closely involved in the alteration of the vascular system.

An exploratory cross-sectional study of subclinical vascular damage in patients with polymyalgia rheumatica

The aim of the study was to investigate the presence of subclinical vascular damage in polymyalgia rheumatica (PMR). We enrolled PMR patients having major cardiovascular risk factors (MCVRF) and, as controls, patients with MCVRF. All underwent: color Doppler ultrasound to evaluate the common carotid intima-media thickness (IMT), the anterior–posterior abdominal aortic diameter (APAD), and the prevalence of carotid artery stenosis; the cardio-ankle vascular index (CAVI) to measure arterial stiffness together with the ankle-brachial index (ABI) to investigate the presence of lower-extremity peripheral arterial disease. Finally, we measured the serum levels of adipocytokines implicated in vascular dysfunction. As a result, 48 PMR and 56 MCVRF patients were included. An increase of IMT (1.07/0.8–1.2 vs 0.8/0.8–1.05; p = 0.0001), CAVI (8.7/7.8–9.3 vs 7.6/6.9–7.8; p < 0.0001) and APAD values (21.15/18.1–25.6 vs 18/16–22; p = 0.0013) was found in PMR patients with respect to controls. No differences were reported in the prevalence of carotid artery stenosis or ABI values between the two groups. A significant correlation between IMT and CAVI in PMR and MCVRF subjects (r2 = 0.845 and r2 = 0.556, respectively; p < 0.01) was found. Leptin levels (pg/mL; median/25th–75th percentile) were higher in PMR than in MCVRF subjects (145.1/67–398.6 vs 59.5/39.3–194.3; p = 0.04). Serum levels of adiponectin (ng/mL) were higher in PMR patients (15.9/10.65–24.1 vs 6.1/2.8–22.7; p = 0.01), while no difference in serum levels of resistin (ng/mL) was found between PMR and MCVRF subjects (0.37/0.16–0.66 vs 0.26/0.14–1.24). Our study shows an increased subclinical vascular damage in PMR patients compared to those with MCVRF, paving the way for further studies aimed at planning primary cardiovascular prevention in this population.

Adipocytokine, leptin, and resistin in combination with quantitative visceral adiposity as predictors of colorectal neoplasm: A case-control study

Background: Substantial evidence has supported the association between adipocytokines and many types of cancers. However, the results in the setting of colorectal cancer (CRC) remains conflicting. Aim: This study aimed to evaluate the predictive power of adipocytokines (leptin and Rrsistin) levels and abdominal fat distribution in the diagnosis of colorectal cancer. Methods: Eighty participants were recruited then divided into three groups based on the endoscopic and histopathological investigation. The recruited individuals included 30 patients with colon cancer, 25 with colonic adenoma, and 25 controls. Serum adipocytokines (leptin and resistin) levels were measured, and the quantitative fat analysis was calculated based on an abdominal CT scan. Results: Multivariable logistic regression revealed that two predictors (leptin and resistin) of CRC development could be used. Visceral/superficial fat rate was the most significant predictor among the parameters of quantitative fat analysis. Also, psoas muscle and visceral fat volume showed significant differences among the study groups. Conclusion: Leptin and resistin can be used as a valuable independent predictor for the diagnosis of colorectal cancer. Also, the visceral/superficial fat rate was the most predictor.

Association between Plasma Adipocytokines Levels and Intracranial Versus Extracranial Atherosclerotic Among Chinese Patients with Stroke

To detect the levels of plasma Adipocytokines, TNF-α, IL-6 and PAI-1 in patients with intracranial and extracranial arteriosclerosis. From September 2015 to September 2017, 318 patients aged ≥60 years were enrolled. Overall, 192 patients were included in the case group (intracranial and extracranial arteriosclerosis group). The 196 outpatients who matched the case groupware selected as the control group. The levels of plasma APN, TNF-α, IL-6 and PAI-1 were measured and their inter- and intra-group comparisons were performed using t-test or analysis of variance. Multivariate logistic regression analysis was used to study the correlation between intracranial arteriosclerosis and extracranial arteriosclerosis. The level of plasma APN in the intracranial and extracranial arteriosclerosis group was significantly lower than that in the control group (P=0.025). The plasma levels of PAI-1, TNF-α and IL-6 were obviously higher than those in the control group (P=0.003, P=0.008, P=0.043). In the intracranial arteriosclerosis group, the level of plasma APN in patients with arterial stenosis ≥70% was significantly lower than that in patients with stenosis 30%-69% (P=0.028). Plasma APN, PAI-1, IL-6 and TNF-α levels can be used as monitoring indicators of intracranial and extracranial arteriosclerosis. Intracranial arteriosclerosis is significantly associated with the decrease of plasma APN level and the increase of plasma PAI- 1, IL-6 and TNF-α levels.

Suppressed immune profile in children with combined type 1 diabetes and celiac disease.

SummaryChildren diagnosed with a combination of type 1 diabetes (T1D) and celiac disease (CD) show a dysregulated T helper type 1 (Th1)/Th17 response. Besides the cellular involvement, several soluble immune markers are involved in the autoimmune process of both T1D and CD. Only few studies have examined the peripheral pattern of different cytokines, chemokines and acute‐phase proteins (APP) in children with combined T1D and CD. To our knowledge, no studies have evaluated the serum levels of adipocytokines and matrix metalloproteinases (MMPs) in this context. The purpose of the present study was to acquire more knowledge and to gain deeper understanding regarding the peripheral immunoregulatory milieu in children with both T1D and CD. The study included children diagnosed with both T1D and CD (n = 18), children with T1D (n = 27) or CD (n = 16) and reference children (n = 42). Sera were collected and analysis of 28 immune markers (cytokines, chemokines, APPs, adipocytokines and MMPs) was performed using the Luminex technique. The major findings showed that children with a double diagnosis had lower serum levels of interleukin (IL)‐22, monocyte chemoattractant protein (MIP)‐1α, monocyte chemoattractant protein (MCP)‐1, procalcitonin, fibrinogen, visfatin and matrix metalloproteinase (MMP)‐2. These results indicate a suppressed immune profile in children with combined T1D and CD, including Th17 cytokines, chemokines, APPs, adipocytokines and MMPs. We conclude that, besides cytokines and chemokines, other immune markers, e.g. APPs, adipocytokines and MMPs, are of importance for further investigations to elucidate the heterogeneous immune processes present in patients diagnosed with T1D in combination with CD.