Plasma factor D is cross-sectionally associated with low-grade inflammation, endothelial dysfunction and cardiovascular disease: The Maastricht study.

BACKGROUND AND AIMS: The complement system, particularly the alternative complement pathway, may contribute to vascular damage and development of cardiovascular disease (CVD). We investigated the association of factor D, the rate-limiting protease in alternative pathway activation, with adverse cardiovascular outcomes. METHODS: In 2947 participants (50.6% men, 59.9 ± 8.2 years, 26.5% type 2 diabetes [T2D], oversampled) we measured markers of low-grade inflammation (LGI, composite score, in SD) and, endothelial dysfunction (ED, composite score, in SD), carotid intima-media thickness (cIMT, µm), ankle-brachial index (ABI), CVD (yes/no) and plasma concentrations of factor D (in SD). Associations were estimated using multiple linear and logistic regression, adjusting for demographic, lifestyle, and dietary factors. RESULTS: Factor D (per SD) significantly associated with LGI (0.171 SD [0.137; 0.205]), ED (0.158 SD [0.123; 0.194]) and CVD (OR 1.15 [1.04; 1.27]) but not significantly with cIMT (-6.62 µm [-13.51; 0.27]) or ABI (-0.003 [-0.007; 0.001]). Interaction analyses show that factor D more strongly associated with ED in non-diabetes (0.237 SD [0.189; 0.285] than in T2D (0.095 SD [0.034; 0.157]), pinteraction <0.05. These results were largely corroborated by additional analyses with C3 and C3a. In contrast, factor D inversely associated with cIMT in non-diabetes (-13.37 µm [-21.84; -4.90]), but not in T2D (4.49 [-7.91; 16.89]), pinteraction <0.05. CONCLUSIONS: Plasma factor D is independently associated with LGI, ED, and prevalent CVD but not with ABI or cIMT. Hence, greater plasma factor D concentration in CVD may potentially induce complement activation which, in turn, might contribute to further disease progression via a process that may involve inflammation and endothelial dysfunction but was not directly related to atherosclerosis or arterial injury. The observation that, in participants without diabetes, factor D associated with worse ED but smaller cIMT warrants further investigation.

Plasma and aqueous levels of alarin and adipsin in patients with and without diabetic retinopathy.

BACKROUND: Diabetic retinopathy is a disease seen with microvascular complications as a result of hyperglycemia and insulin resistance. Alarin and Adipsin are molecules with a role in energy and glucose metabolism. The aim of this study was to determine plasma and aqueous levels of Alarin and Adipsin in patients with and without diabetic retinopathy to evaluate their potential roles in diabetic retinopathy. METHODS: The study included one eye from each of 20 cataract patients without diabetes (C), 20 cataract patients with diabetes and without diabetic retinopathy (DM + C), and 20 cataract patients with diabetes and diabetic retinopathy (DR + C). Plasma and aqueous humour samples were taken from all patients during the cataract operation. Alarin and Adipsin levels were examined with the enzyme-linked immunosorbent assay (ELISA) method. RESULTS: Both plasma and aqueous Alarin levels were significantly higher in the patients with diabetic retinopathy than in the control group (p < 0.001, p = 0.006). Adipsin levels were found to be significantly higher in plasma in the control group than in the DR + C group and significantly higher in aqueous in the DR + C group than in the control group (p < 0.001, p < 0.001). CONCLUSION: These findings suggest that Alarin and Adipsin may play important role in diabetic retinopathy.

Inverse Association of Serum Adipsin with the Remission of Nonalcoholic Fatty-Liver Disease: A 3-Year Community-Based Cohort Study.

PURPOSES: Adipokine alterations contribute to the development and remission of nonalcoholic fatty-liver disease (NAFLD). Adipsin is one of the most abundant adipokines and is almost exclusively produced by adipocytes. However, data on adipsin in human NAFLD are limited and controversial. We performed this study to investigate the association between adipsin and the remission of NAFLD in middle-aged and elderly Chinese adults. METHODS: Whether adipsin is associated with the remission of NAFLD in a 3-year community-based prospective cohort study was investigated. Baseline levels of adipsin were measured in serum samples collected from 908 NAFLD participants. NAFLD was diagnosed using abdominal ultrasonography. Logistic regression analysis and a multiple stepwise logistic regression model including different variables were conducted to evaluate the association between serum adipsin levels and the remission of NAFLD. RESULTS: During a mean follow-up of 3.14 ± 0.36 years, 247 (27.20%) participants with NAFLD at baseline were in remission. At baseline, serum adipsin concentration was positively correlated with body mass index (r: 0.39, p < 0.001), insulin (r: 0.31, p < 0.001), and homeostasis model assessment of insulin resistance (r: 0.31, p < 0.001) and was inversely associated with NAFLD remission with a fully adjusted odds ratio (OR) of 0.28 (0.16-0.48) (p trend < 0.001). In a multiple stepwise logistic regression model, circulating adipsin independently predicted NAFLD remission (OR: 0.284, 95% confidence interval [CI]: 0.172-0.471, p for trend <0.001). The area under the receiver operating characteristic curve was 0.751 (95% CI: 0.717-0.785) (p < 0.001) for the prediction model of NAFLD remission. CONCLUSIONS: We provide evidence for an association between serum adipsin levels and the remission of NAFLD in a community-based prospective cohort study. Serum adipsin can be a potential biomarker for predicting NAFLD remission.

Circulating adipsin is associated with asymptomatic carotid atherosclerosis in obese adults.

BACKGROUND: Adipsin has been identified as a secreted adipokine that plays a critical pathogenic role in metabolic disorders. However, it is not clear regarding the association of circulating adipsin with cardiovascular disease (CVD). This study will explore the association between circulating adipsin and asymptomatic carotid atherosclerosis in Chinese obese adults. METHODS: A total of 483 obese adult subjects (aged 40 years or older) were enrolled in this study. Serum adipsin concentrations and carotid intima-media thickness (CIMT) were measured to determine these associations. RESULTS: Individuals with increased CIMT and asymptomatic carotid atherosclerosis had lower levels of circulating adipsin than controls (both p < 0.05). The prevalence of asymptomatic carotid atherosclerosis was significantly higher in subjects with lower levels of serum adipsin than those with higher values (42.5% vs. 36.7%, p < 0.05). Notably, subjects in the lowest quartile of serum adipsin were 1.94 times (p = 0.059) more likely to have increased CIMT and 2.91 times (p = 0.03) more likely to have asymptomatic carotid atherosclerosis than those in the highest quartile in multivariable logistic regression analyses, adjusting for age, gender, current smoking, alcohol consumption, physical activity, BMI, systolic BP, fasting glucose, total cholesterol, HDL-c, and HOMA-IR. However, such associations with circulating adipsin were not noted for atherosclerotic plaque. CONCLUSIONS: These findings suggest that circulating adipsin concentrations are a potential marker of risks of increased CIMT and asymptomatic carotid atherosclerosis in obese Chinese adults.

Diagnostic and Prognostic Significance of Complement in Patients With Alcohol-Associated Hepatitis.

BACKGROUND AND AIMS: Given the lack of effective therapies and high mortality in acute alcohol-associated hepatitis (AH), it is important to develop rationally designed biomarkers for effective disease management. Complement, a critical component of the innate immune system, contributes to uncontrolled inflammatory responses leading to liver injury, but is also involved in hepatic regeneration. Here, we investigated whether a panel of complement proteins and activation products would provide useful biomarkers for severity of AH and aid in predicting 90-day mortality. APPROACH AND RESULTS: Plasma samples collected at time of diagnosis from 254 patients with moderate and severe AH recruited from four medical centers and 31 healthy persons were used to quantify complement proteins by enzyme-linked immunosorbent assay and Luminex arrays. Components of the classical and lectin pathways, including complement factors C2, C4b, and C4d, as well as complement factor I (CFI) and C5, were reduced in AH patients compared to healthy persons. In contrast, components of the alternative pathway, including complement factor Ba (CFBa) and factor D (CFD), were increased. Markers of complement activation were also differentially evident, with C5a increased and the soluble terminal complement complex (sC5b9) decreased in AH. Mannose-binding lectin, C4b, CFI, C5, and sC5b9 were negatively correlated with Model for End-Stage Liver Disease score, whereas CFBa and CFD were positively associated with disease severity. Lower CFI and sC5b9 were associated with increased 90-day mortality in AH. CONCLUSIONS: Taken together, these data indicate that AH is associated with a profound disruption of complement. Inclusion of complement, especially CFI and sC5b9, along with other laboratory indicators, could improve diagnostic and prognostic indications of disease severity and risk of mortality for AH patients.

A prospective study in women: açaí (Euterpe oleracea Martius) dietary intake affects serum p-selectin, leptin, and visfatin levels.

INTRODUCTION: Background: açaí is the fruit of the palm tree Euterpe oleracea Martius, which is native to the Amazon region. This fruit has been extensively studied due to its potential effects on human health. Studies have also evaluated the potential effect of açaí on the inflammatory response, but there are still few studies that have assessed this property in humans. Objective: in this study we aimed to evaluate the effects of 200 g of açaí pulp consumption per day during four weeks on a rich panel of inflammatory biomarkers. Methods: a prospective nutritional intervention study was conducted on forty apparently healthy women who consumed 200 g of açaí pulp per day for four weeks. A panel of serum inflammatory markers were evaluated before and after the nutritional intervention, namely, cell adhesion molecules (ICAM-1, IVAM-1, P-selectin, MCP-1, and fractalkine), interleukins (IL-1ß, IL-6, IL-8, IL-10, and IL-17) and adipokines (adiponectin, leptin, visfatin, and adipsin). The data were analyzed using paired Student's t-test to evaluate the effect of the intervention using PASW Statistics, version 17.0, and a p-value of < 0.05 was considered significant. Results: four weeks of açaí pulp consumption decreased p-selectin, leptin, and visfatin concentrations in the serum of the participating women. Conclusion: these results show that consumption of açaí pulp was able to modulate important biomarkers of the inflammatory process in apparently healthy women.

INTRODUCCIÓN: Introducción: el açaí es el fruto de la palmera Euterpe oleracea Martius, originaria de la región amazónica. Esta fruta ha sido ampliamente estudiada debido a sus posibles efectos sobre la salud humana. Los estudios también han evaluado el efecto potencial del açaí sobre la respuesta inflamatoria, pero todavía hay pocos estudios que hayan evaluado esta propiedad en seres humanos. Objetivo: en este estudio, nuestro objetivo ha sido evaluar los efectos del consumo de 200 g de pulpa de açaí por día durante cuatro semanas sobre un rico panel de biomarcadores inflamatorios. Métodos: se ha realizado un estudio prospectivo de intervención nutricional en el que cuarenta mujeres aparentemente sanas han consumido 200 g de pulpa de açaí al día durante cuatro semanas. Se ha evaluado un panel de marcadores inflamatorios séricos antes y después de la intervención nutricional, a saber, moléculas de adhesión celular (ICAM-1, IVAM-1, P-selectina, MCP-1 y fractalquina), interleucinas (IL-1ß, IL-6, IL-8, IL-10 e IL-17) y adipocinas (adiponectina, leptina, visfatina y adipsina). Los datos han sido analizados mediante la prueba de la t de Student pareada para evaluar el efecto de la intervención mediante el PASW Statistics, versión 17.0, y todo valor de p < 0,05 se consideró significativo. Resultados: después de cuatro semanas de consumo de pulpa de açaí disminuyeron las concentraciones de p-selectina, leptina y visfatina en el suero de las mujeres participantes. Conclusión: estos resultados muestran que el consumo de pulpa de açaí ha sido capaz de modular importantes biomarcadores del proceso inflamatorio en mujeres aparentemente sanas.

Plasma levels of adipokines in patients with Alzheimer's disease - where is the "breaking point" in Alzheimer's disease pathogenesis?

Peripheral insulin resistance is associated with decreasing adiponectin and increasing leptin plasma levels, and also with cognitive decline. The effects of adipokines on brain function have been published from both animal and human studies. In particular, the influence of leptin and adiponectin on the development of Alzheimer's disease (AD) has been extensively investigated. However, the association between adipsin and AD is as yet unknown. In 37 patients with AD and 65 controls that followed the same study protocol, we tested whether adiponectin, leptin, and adipsin could be used as biomarkers in the early stages of AD. In contrast with conclusions of cognition studies in insulin resistant states, our study found a correlation of impaired neuropsychological performance with increasing adiponectin and decreasing leptin in AD patients. Nevertheless, no significant differences between patients and controls were found. AD women had significantly increased adipsin compared to controls, and there was a positive correlation of adipsin with age and disease duration. Although adipokines do not appear to be suitable biomarkers for early AD diagnosis, they certainly play a role in the pathogenesis of AD. Further studies will be needed to explain the cause of the adipokine "breaking point" that leads to the pathogenesis of overt AD.

Exploring the role of adipsin in statin-induced glucose intolerance: a prospective open label study.

Background Evidence from the literature, highlights the increased risk of developing glucose intolerance and type 2 diabetes mellitus (T2DM) with statin therapy. In addition, few animal studies demonstrate that adipsin secreted from adipocytes plays a crucial role in insulin secretion and the development of T2DM. Methods To further explore the role of serum adipsin, in this prospective open label study, 55 newly diagnosed dyslipidemic patients were enrolled. Before starting statin therapy, liver function test (LFT), kidney function test (KFT), lipid profile, glycemic parameters [glycated hemoglobin A (HbA1c), fasting blood sugar (FBS), and postprandial blood sugar (PPBS)], serum insulin, and serum adipsin were estimated. Then these patients were prescribed statin (i.e. atorvastatin, rosuvastatin, or pitavastatin) and after 12 weeks of therapy, all the above investigations were repeated. Results After 12 weeks of statin therapy, the LFT and KFT values remained unchanged and lipid parameters showed significant improvement. But the glycemic parameters deranged significantly (p < 0.001), i.e. FBS, PPBS, and HbA1c increased by 12.49% (102.99 ± 20.76 mg/dL), 24.72% (147.71 ± 47.29 mg/dL), and 21.43% (6.38 ± 1.34%), respectively. On the other hand, the baseline adipsin (2.73 ± 1.99 ng/mL) and insulin (16.13 ± 12.50 mIU/L) levels reduced significantly (p < 0.0001) to 1.43 ±1.13 ng/mL and 6.91 ± 5.93 mIU/L, respectively. The reduction in serum adipsin also showed a positive correlation with reduction in serum insulin (r = 0.85; p < 0.0001). None of the patients experienced any significant adverse effect or reaction leading to discontinuation of therapy. Conclusions There might be an association between reduction in adipsin and development of glucose intolerance by statin therapy.

Identification of Adipsin as a Novel Prognostic Biomarker in Patients With Coronary Artery Disease.

Background Circulating proteins are exposed to vascular endothelial layer and influence their functions. Among them, adipsin is a member of the trypsin family of peptidases and is mainly secreted from adipocytes, monocytes, and macrophages, catalyzing the rate-limiting step of the alternative complement pathway. However, its pathophysiological role in cardiovascular disease remains to be elucidated. Here, we examined whether serum adipsin levels have a prognostic impact in patients with coronary artery disease. Methods and Results In 370 consecutive patients undergoing diagnostic coronary angiography, we performed a cytokine array analysis for screening serum levels of 50 cytokines/chemokines and growth factors. Among them, classification and regression analysis identified adipsin as the best biomarker for prediction of their long-term prognosis (median 71 months; interquartile range, 55-81 months). Kaplan-Meier curve showed that higher adipsin levels (≥400 ng/mL) were significantly associated with all-cause death (hazard ratio [HR], 4.2; 95% CI, 1.7-10.6 [P<0.001]) and rehospitalization (HR, 2.4; 95% CI, 1.7-3.5 [P<0.001]). Interestingly, higher high-sensitivity C-reactive protein levels (≥1 mg/L) were significantly correlated with all-cause death (HR, 3.2; 95% CI, 1.7-5.9 [P<0.001]) and rehospitalization (HR, 1.5, 95% CI, 1.1-1.9 [P<0.01]). Importantly, the combination of adipsin (≥400 ng/mL) and high-sensitivity C-reactive protein (≥1 mg/L) was more significantly associated with all-cause death (HR, 21.0; 95% CI, 2.9-154.1 [P<0.001]). Finally, the receiver operating characteristic curve demonstrated that serum adipsin levels predict the death caused by acute myocardial infarction in patients with coronary artery disease (C-statistic, 0.847). Conclusions These results indicate that adipsin is a novel biomarker that predicts all-cause death and rehospitalization in patients with coronary artery disease, demonstrating the novel aspects of the alternative complementary system in the pathogenesis of coronary artery disease.

Immunoaffinity LC-MS/MS to quantify a PEGylated anti-Factor D Fab biotherapeutic in cynomolgus monkey serum.

Aim: To develop a sensitive hybrid immunoaffinity LC-MS/MS monkey serum assay to quantify multiple components of anti-Factor D; a complex PEGylated Fab biotherapeutic explored as a therapy for age-related macular degeneration. Materials & methods: Immunoaffinity enrichment of PEGylated anti-Factor D Fab, including fully conjugated, partially conjugated and unconjugated (i.e., free) Fab species, using a capture reagent coupled to magnetic beads was performed. The surrogate peptides derived from the therapeutic Fab via trypsin digestion were measured to obtain the total Fab concentrations. Results & conclusion: The method demonstrated the ability to accurately quantify both PEGylated and unconjugated Fab species. It was successfully validated with a LLOQ at 25.0 ng/ml.

Association between plasma adipsin level and mild cognitive impairment in Chinese patients with type 2 diabetes: a cross-sectional study.

BACKGROUND: The adipokine adipsin contributes to insulin resistance (IR), inflammation, and obesity, which are all regarded as high-risk factors for mild cognitive impairment (MCI) in patients with type 2 diabetes mellitus. This research aimed to uncover the role of adipsin in Chinese type 2 diabetes mellitus (T2DM) population with early cognitive dysfunction and determine whether adipsin contributes to diabetic MCI caused by IR. METHODS: In our study, 126 patients with T2DM were enrolled. The Montreal Cognitive Assessment (MoCA) was used to assess cognitive impairment. Demographic data and neuropsychological test results were evaluated. Plasma adipsin level was measured by enzyme-linked immunosorbent assay. RESULTS: The MCI group (n = 57) presented higher plasma adipsin levels compared with the healthy controls (p = 0.018). After adjustment for educational attainment, and age, begative correlations were found between plasma adipsin levels and MoCA, Mini Mental State Exam, and Verbal Fluency Test scores(r = - 0.640, p < 0.001; r = - 0.612, p < 0.001; r = - 0.288, p = 0.035; respectively). Correlation analysis demonstrated that adipsin levels were significantly positively correlated with fasting C-peptide; homeostasis model of assessment for insulin resistance (HOMA-IR) (r = 0.368, p < 0.001; r = 0.494, p < 0.001; respectively). Multivariable regression analysis further indicated that high plasma adipsin level was a significant independent determinant of MCI in the Chinese population withT2DM (p = 0.017). CONCLUSIONS: Elevated plasma adipsin level was associated with MCI in Chinese T2DM patients. Further large-scale studies should be designed to determine whether adipsin is linked to IR-associated susceptibility to early cognitive decline in T2DM patients.

Administration of Intravenous Iron Formulations Induces Complement Activation in-vivo.

Background: Intravenous (IV) iron is widely used to treat anemia in chronic kidney disease patients. Previously, iron formulations were shown to induce immune activation in-vitro. The current study aimed to investigate the effect of IV iron on complement activation in-vivo, and whether this subsequently induces inflammation and/or oxidative stress. Methods: Two distinct patient groups were included: 51 non-dialysis and 32 dialysis patients. The non-dialysis group received iron sucrose or ferric carboxymaltose, based on physicians' choice. Plasma samples were collected prior to and 1 h after completion of IV iron infusion. The dialysis group received iron sucrose exclusively. Plasma samples were collected at the start and end of two consecutive hemodialysis sessions, one with and one without IV iron. Finally, plasma levels of MBL, C1q, properdin, factor D, sC5b-9, MPO, PTX3 were assessed by ELISA. Results: In the non-dialysis group, sC5b-9 levels significantly increased after IV iron by 32%, while levels of factor D and MBL significantly dropped. Subgroup analysis demonstrated that iron sucrose induced complement activation whereas ferric carboxymaltose did not. In the dialysis group, levels of sC5b-9 significantly increased by 46% during the dialysis session with IV iron, while factor D levels significantly fell. Furthermore, the relative decrease in factor D by IV iron correlated significantly with the relative increase in sC5b-9 by IV iron. MPO levels rose significantly during the dialysis session with IV iron, but not in the session without iron. Moreover, the relative increase in MPO and sC5b-9 by IV iron correlated significantly. PTX3 levels were not affected by IV iron. Conclusions: Iron sucrose but not ferric carboxymaltose, results in complement activation possibly via the lectin and alternative pathway partially mediating oxidative stress but not inflammation.

The ratio adipsin/MCP-1 is strongly associated with structural changes and CRP/MCP-1 with symptoms in obese knee osteoarthritis subjects: data from the Osteoarthritis Initiative.

OBJECTIVE: There is a need to identify reliable biomarkers that can predict knee osteoarthritis (OA) progression. We investigated a panel of adipokines and some related inflammatory factors alone and their ratios for their associative value at assessing cartilage volume loss over time and symptoms in obese [High body mass index (BMI)] and non-obese (Low BMI) OA subjects. DESIGN: Human OA serum was from the Osteoarthritis Initiative Progression subcohort. Baseline levels of adiponectin (high and low molecular weight forms), adipsin, chemerin, leptin, visfatin, C-reactive protein (CRP), interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) were evaluated with specific assays. Cartilage volume was assessed at baseline and 48 months by quantitative magnetic resonance imaging (MRI), and symptoms using baseline Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores. Data were analysed by linear regression with confounding factors at baseline, followed by multiple comparison adjustment. RESULTS: The levels of the nine biomarkers and their ratios (36) were studied. Among High BMI subjects, only the ratio adipsin/MCP-1 was associated with cartilage volume loss over time in the lateral compartment [ß, -2.95; 95% confidence interval (CI), -4.42, -1.49; P = 0.010], whereas MCP-1 was associated with WOMAC pain (-1.74; -2.75, -0.73; P = 0.030) and the ratio CRP/MCP-1 with WOMAC pain (0.76; 0.37, 1.14; P = 0.023), function (2.43; 1.20, 3.67; P = 0.020) and total (3.29; 1.58, 5.00; P = 0.027). No associations were found for biomarkers or ratios in Low BMI OA. CONCLUSION: In this study, the ratio adipsin/MCP-1 was found to be associated with the knee structural changes and that of CRP/MCP-1 with symptoms in obese OA subjects. Our data further underline the relevance of ratios as biomarkers to a stronger association to OA progression and symptoms.

Coexistence of obstructive sleep apnea and telomerase activity, concentration of selected adipose tissue hormones and vascular endothelial function in patients with arterial hypertension.

AIM: The aim of the present study was to determine the effect of obstructive sleep apnea (OSA) with hypertension on telomerase activity, visfatin and adipsine concentration in the blood and vascular endothelial function assessed by ultrasound measured flow-mediated dilatation of the brachial artery (FMD). MATERIAL AND METHODS: The study involved a group of 106 people (average age: 54.79 years). The determination of telomerase activity and blood visfatin and adipsine concentrations, brachial artery ultrasound examination with endothelium-dependent dilatation evaluation (FMD) and polysomnography were carried out. RESULTS: Patients with hypertension without OSA were characterized by significantly greater FMD in comparison to patients with arterial hypertension and OSA (8.13 ±â€¯5.12 %vs. 6.82 ±â€¯5.36%; p < 0.05). Negative linear relationship between apnea-hypopnea index (AHI) and FMD (r = -0.22, p < 0.05) has been demonstrated. Negative linear relationship between adipsine concentration in the blood and length of REM (Rapid Eye Movement) sleep (r = -0.21, p < 0.05) was found. Positive linear relationship between the concentration of visfatin in the blood and the length of REM sleep (r = 0.22, p < 0.05) was also observed. Higher body mass index, higher total cholesterol, triglyceride and glucose levels have been shown to be independent predictors of higher AHI values, while greater telomerase activity, greater FMD and use of angiotensin converting enzyme inhibitors are independent predicators for lower AHI values. CONCLUSION: Higher values of AHI index in polysomnography in hypertensive patients can be related to lower telomerase activity in the blood and impaired function of vascular endothelial function assessed using ultrasound.

Association of Circulating Adipsin, Visfatin, and Adiponectin with Nonalcoholic Fatty Liver Disease in Adults: A Case-Control Study.

BACKGROUND/AIMS: Some adipokines, such as adiponectin and leptin, have been reported to be involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), while the association of adipsin and visfatin with NAFLD still remains unclear. This study aimed to examine the association of circulating adipsin, visfatin, and adiponectin with NAFLD in Chinese adults. METHODS: We recruited a total of 211 eligible subjects, including 100 NAFLD cases and 111 age and sex frequency-matched controls. Circulating adipsin, visfatin, and adiponection concentrations were measured by enzymatic immunoassay. Unconditional logistic regression was conducted to assess the associations between quartiles of adipokines and NAFLD. RESULTS: Compared with the controls, NAFLD cases had higher levels of adipsin and lower levels of visfatin and adiponectin. By multivariate logistic analysis, adjusting for potential confounders, circulating adipsin levels were found to be positively associated with NAFLD risk, and circulating levels of visfatin and adiponectin were inversely associated with the risk of NAFLD (all p-trend < 0.05). The ORs were 3.76 (95% CI 1.27-11.08) for adipsin, 0.30 (95% CI 0.10-0.91) for visfatin, and 0.30 (95% CI 0.10-0.88) for adiponectin comparing subjects in the highest quartile with those in the lowest. After stratified by obesity status, the association of higher adipsin with increased risk of NAFLD was only observed in nonobese group. Additionally, the inverse association between adiponectin and NAFLD was found in both groups. CONCLUSIONS: These results indicated that increased circulating levels of adipsin and decreased circulating levels of visfatin and adiponectin were independently associated with the increased risk of NAFLD.

Vitamin D supplementation and inflammatory and metabolic biomarkers in patients with knee osteoarthritis: post hoc analysis of a randomised controlled trial.

The aim of this study was to determine whether vitamin D supplementation and maintaining vitamin D sufficiency are associated with changes in inflammatory and metabolic biomarkers in patients with knee osteoarthritis (OA) and vitamin D deficiency. A total of 413 participants with symptomatic knee OA and vitamin D deficiency were enrolled in a randomised, placebo-controlled trial and received 1·25 mg vitamin D3 or placebo monthly for 24 months across two sites. In this post hoc analysis, 200 participants from one site (ninety-four from the placebo group and 106 from the vitamin D group; mean age 63·1 (sd 7·3) years, 53·3 % women) were randomly selected for measurement of serum levels of inflammatory and metabolic biomarkers at baseline and 24 months using immunoassays. In addition, participants were classified into two groups according to serum 25-hydroxyvitamin D (25(OH)D) levels at months 3 and 24: (1) not consistently sufficient (25(OH)D≤50 nmol/l at either month 3 or 24, n 61), and (2) consistently sufficient (25(OH)D>50 nmol/l at both months 3 and 24, n 139). Compared with placebo, vitamin D supplementation had no significant effect on change in serum high-sensitive C-reactive protein, IL-6, IL-8, IL-10, leptin, adiponectin, resistin, adipsin and apelin. Being consistently vitamin D sufficient over 2 years was also not associated with changes in these biomarkers compared with not being consistently sufficient. Vitamin D supplementation and maintaining vitamin D sufficiency did not alter serum levels of inflammatory and metabolic biomarkers over 2 years in knee OA patients who were vitamin D insufficient, suggesting that they may not affect systemic inflammation in knee OA patients.

Contribution of Adipose-Derived Factor D/Adipsin to Complement Alternative Pathway Activation: Lessons from Lipodystrophy.

Factor D (FD) is an essential component of the complement alternative pathway (AP). It is an attractive pharmaceutical target because it is an AP-specific protease circulating in blood. Most components of the complement activation pathways are produced by the liver, but FD is highly expressed by adipose tissue. Two critical questions are: 1) to what degree does adipose tissue contribute to circulating FD levels and 2) what quantity of FD is sufficient to maintain a functional AP? To address these issues, we studied a novel mouse strain with complete lipodystrophy (LD), the fld mouse with partial LD, an FD-deficient mouse, and samples from lipodystrophic patients. FD was undetectable in the serum of LD mice, which also showed minimal AP function. Reconstitution with purified FD, serum mixing experiments, and studies of partial LD mice all demonstrated that a low level of serum FD is sufficient for normal AP activity in the mouse system. This conclusion was further supported by experiments in which wild-type adipose precursors were transplanted into LD mice. Our results indicate that almost all FD in mouse serum is derived from adipose tissue. In contrast, FD levels were reduced ∼50% in the sera of patients with congenital generalized LD. Our studies further demonstrate that a relatively small amount of serum FD is sufficient to facilitate significant time-dependent AP activity in humans and in mice. Furthermore, this observation highlights the potential importance of obtaining nearly complete inhibition of FD in treating alternative complement activation in various autoimmune and inflammatory human diseases.

Relationship between serum adipsin and the first phase of glucose-stimulated insulin secretion in individuals with different glucose tolerance.

AIMS/INTRODUCTION: To detect serum adipsin levels in individuals with different glucose tolerance, and investigate the relationship between adipsisn and the first phase of insulin secretion. MATERIALS AND METHODS: A total of 56 patients with newly diagnosed type 2 diabetes mellitus, 36 patients with impaired glucose tolerance (IGT) and 45 individuals with normal glucose tolerance were enrolled. Intravenous glucose tolerance tests were carried out to evaluate pancreatic ß-cell function. The serum levels of adipsin, interleukin-1ß and high-sensitivity C-reactive protein were assayed. RESULTS: Serum adipsin levels were significantly lower in the type 2 diabetes mellitus and the IGT patients than those in the normal glucose tolerance group (P < 0.05). The acute insulin response and area under the curve showed a progressive decrease in the normal glucose tolerance and IGT groups, and decreased to the lowest levels in the type 2 diabetes mellitus group (P < 0.05). Adipsin was found to be negatively correlated with waist-to-hip ratio, free fatty acid, fasting plasma glucose, 2-h postprandial plasma glucose, glycated hemoglobin, homeostasis model assessment of insulin resistance, interleukin-1ß and high-sensitivity C-reactive protein (P < 0.05 or P < 0.001), and positively correlated with homeostasis model assessment of ß-cell function, high-density lipoprotein cholesterol, the area under the curve of the first phase insulin secretion and acute insulin response (P < 0.05 or P < 0.001). Stepwise multiple regression analysis showed that homeostasis model assessment for ß-cell function and acute insulin response were independently related to adipsin (P < 0.05). CONCLUSIONS: Serum adipsin levels were lower in type 2 diabetes mellitus and IGT patients, and correlated with the first phase of insulin secretion. Adipsin might be involved in the pathology of type 2 diabetes mellitus.

Elevated serum adipsin may predict unsuccessful treatment for cows' milk allergy but other biomarkers do not.

AIM: This study evaluated whether 15 allergy, immunology or inflammatory markers predicted the long-term use of cows' milk or milk products seven years after the start of oral immunotherapy (OIT) for cows' milk allergy in children. METHODS: The following laboratory parameters were measured before the OIT at Tampere University Hospital, Finland, and after the six-month escalation phase: serum total immunoglobulin (Ig) E, milk-specific IgG and IgG4, eosinophil cationic protein, eosinophil-derived neurotoxin, interleukins 4, 5, 6, 10 and 12p70 and serum adipokines adiponectin, adipsin, leptin and resistin. Follow-up data from a seven-year phone questionnaire in 2015 were available for 24 children: 14 successful and 10 unsuccessful milk users. RESULTS: There were no significant differences in any of the 15 markers measured at the start of the study between the subjects who later formed the successful and unsuccessful groups. At the end of the six-month escalation phase of OIT, serum adipsin was higher in the group who were unsuccessful milk users at the seven-year follow-up study. CONCLUSION: None of the 15 allergy, immunology or inflammatory markers were useful in predicting the outcome of OIT. Preliminary evidence was found that high serum adipsin after the six-month escalation phase of OIT might predict unsuccessful outcome.

Increased adipsin is associated with carotid intima media thickness and metabolic disturbances in polycystic ovary syndrome.

CONTEXT: Adipsin, a protein secreted mainly from the adipose tissue, is a structural homologous of complement factor D, a rate-limiting enzyme of the alternative complement system. Growing evidence suggests that the alternative complement system plays a role both in the regulation of energy homoeostasis and in the atherosclerosis. Polycystic ovary syndrome (PCOS) is a reproductive and metabolic disease. OBJECTIVE: To ascertain whether circulating adipsin levels are altered in women with PCOS, and whether there is an association between adipsin and metabolic parameters or carotid intima media thickness (CIMT). PARTICIPANTS: A total of 144 women with PCOS and 144 age- and BMI-matched controls without PCOS were recruited for this cross-sectional study. MAIN OUTCOME MEASURES: Circulating adipsin levels were measured using ELISA. Metabolic, hormonal parameters and CIMT were also determined. RESULTS: Adipsin levels were significantly elevated in women with PCOS compared with controls (91·52 ± 14·11 vs 60·31 ± 9·71 ng/ml, P < 0·001). Adipsin positively correlated with BMI, homoeostasis model assessment of insulin resistance (HOMA-IR), free testosterone, high-sensitivity C-reactive protein (hs-CRP) and CIMT in both groups. Multivariate logistic regression analyses revealed that the odds ratio for PCOS was 3·25 for patients in the highest quartile of adipsin compared with those in the lowest quartile (OR=3·25, 95% CI=2·64-4·00, P = 0·016). Our findings further indicate that BMI, HOMA-IR, hs-CRP and free testosterone are independent factors influencing serum adipsin levels and that adipsin is an independent predictor for CIMT. CONCLUSION: Circulating adipsin levels are significantly higher in women with PCOS, and the peptide is closely related to increased cardiovascular risk and metabolic disturbances.