Comparative effects of 8-week combined resistance exercise training and alternate-day calorie restriction on soluble epidermal growth factor receptor (sEGFR) and adipsin in obese men.

This study investigated the combined effects of resistance exercise training (RET) and alternate-day calorie restriction (ADCR) on body composition, insulin resistance (IR), insulin resistance-related biomarkers (adipokine adipsin and hepatokine soluble EFGR), and weight loss in obese men. The findings revealed that RET + ADCR induced the greatest reductions in body weight, body fat percentage, and waist-to-hip ratio (WHR) compared to RET and ADCR alone (p < 0.05). Additionally, RET + ADCR resulted in the most significant improvements in IR, as measured by HOMA-IR, and in circulating levels of adipsin and soluble EFGR (p < 0.05). These findings suggest that combining RET and ADCR may be a more effective strategy for improving metabolic health, including body composition, IR, and metabolic tissues' functions, in obese men than either intervention alone.

Association of Serum Adipsin Level with Insulin Resistance and Inflammatory Markers in Newly Diagnosed Type two Diabetes Mellitus Patients.

Adipsin is an anti-inflammatory adipokines and its altered level was seen in obesity and type II DM. Our study investigated the clinical significance of serum adipsin levels as a risk marker for type 2 diabetes and its relationships with insulin resistance and various adipo-cytokines. The study included 110 treatment-naïve T2DM cases and 100 controls of similar age and gender from northern India. Clinical, biochemical, and anthropometric characteristics were all profiled. Serum adipo-cytokines were measured using ELISA methods. Adipsin was significantly inversely correlated with body mass index (BMI), waist circumference, fasting plasma glucose, glycated haemoglobin (HbA1C), total cholesterol (TC), triglyceride (TG), homeostasis model assessment-estimated insulin resistance (HOMA-IR), tumour necrosis factor- α (TNF-α) and interleulin-6 (IL-6) and positively correlated with high-density lipoprotein cholesterol (HDL-C) and homeostasis model assessment of ß-cell function (HOMA-B) (P < 0.05). T2DM occurrence decreased with increasing concentration of adipsin with an odds ratio (OR) of 0.68 (95% CI = 0.58-0.79), P < 0.001. The area under curve (95% CI) for adipsin was 0.70 (0.63 to 0.76) with P < 0.001. The best cutoff value for adipsin to predict T2DM was < 5.50 µg/ml with 47.27% sensitivity and 82.00% specificity. FPG and WC were both independent predictors of serum adipsin levels. Our findings showed that high adipsin levels reduced the likelihood of T2DM and emerged as a potential risk marker in the prediction of T2DM.

Adipsin in the pathogenesis of cardiovascular diseases.

Adipsin is an adipokine predominantly synthesized in adipose tissues and released into circulation. It is also known as complement factor-D (CFD), acting as the rate-limiting factor in the alternative complement pathway and exerting essential functions on the activation of complement system. The deficiency of CFD in humans is a very rare condition. However, complement overactivation has been implicated in the etiology of numerous disorders, including cardiovascular disease (CVD). Increased circulating level of adipsin has been reported to promote vascular derangements, systemic inflammation, and endothelial dysfunction. Prospective and case-control studies showed that this adipokine is directly associated with all-cause death and rehospitalization in patients with coronary artery disease. Adipsin has also been implicated in pulmonary arterial hypertension, abdominal aortic aneurysm, pre-eclampsia, and type-2 diabetes which is a major risk factor for CVD. Importantly, serum adipsin has been recognized as a unique prognostic marker for assessing cardiovascular diseases. At present, there is paucity of experimental evidence about the precise role of adipsin in the etiology of CVD. However, this mini review provides some insight on the contribution of adipsin in the pathogenesis of CVD and highlights its role on endothelial, smooth muscle and immune cells that mediate cardiovascular functions.

The profile of adipokines associated with fibrosis and impaired microcirculation in systemic sclerosis.

PURPOSE: Adipokines belong to a group of molecules mostly produced by adipose tissue. Abnormalities in the secretion of several adipokines have already implicated to play a pathogenic role in systemic sclerosis (SSc). However, the possible role of numerous molecules still needs to be clarified. The aim of the study was to determine whether the altered level of selected circulating adipokines might correlate with the intensity of fibrosis and vasculopathy in the course of SSc. MATERIALS AND METHODS: Serum concentrations of chemerin, adipsin, retinol-binding protein 4, apelin, visfatin, omentin-1, and vaspin were determined with ELISA in the sera of patients with SSc (n â€‹= â€‹55) and healthy controls (n â€‹= â€‹25). RESULTS: The serum concentration of adipsin (p â€‹= â€‹0.03) and visfatin (p â€‹= â€‹0.04) was significantly increased and the level of retinol-binding protein 4 (p â€‹= â€‹0.03) was decreased in diffuse compared to limited cutaneous SSc. Moreover, serum adipsin level correlated positively with the intensity of skin fibrosis measured with the modified Rodnan skin score (r â€‹= â€‹0.31, p â€‹= â€‹0.02) and was significantly higher in patients with pulmonary arterial hypertension than in those without the condition (p â€‹= â€‹0.03). The concentrations of adipsin (p â€‹= â€‹0.01) and visfatin (p â€‹= â€‹0.04) were significantly increased and the level of apelin (p â€‹= â€‹0.02) was decreased in patients with active digital ulcerations compared to individuals without this complication. CONCLUSION: Adipsin may be considered a pivotal protein in the development of both fibrosis and impaired microcirculation. Its abnormal concentration reflects the intensity of skin thickening and the presence of pulmonary arterial hypertension. Adipsin, visfatin, and apelin are adipose tissue-derived molecules associated with digital vasculopathy.

Adipocyte regulation of cancer stem cells.

Cancer stem cells (CSCs) are a highly tumorigenic subpopulation of the cancer cells within a tumor that drive tumor initiation, progression, and therapy resistance. In general, stem cell niche provides a specific microenvironment in which stem cells are present in an undifferentiated and self-renewable state. CSC niche is a specialized tumor microenvironment for CSCs which provides cues for their maintenance and propagation. However, molecular mechanisms for the CSC-niche interaction remain to be elucidated. We have revealed that adipsin (complement factor D) and its downstream effector hepatocyte growth factor are secreted from adipocytes and enhance the CSC properties in breast cancers in which tumor initiation and progression are constantly associated with the surrounding adipose tissue. Considering that obesity, characterized by excess adipose tissue, is associated with an increased risk of multiple cancers, it is reasonably speculated that adipocyte-CSC interaction is similarly involved in many types of cancers, such as pancreas, colorectal, and ovarian cancers. In this review, various molecular mechanisms by which adipocytes regulate CSCs, including secretion of adipokines, extracellular matrix production, biosynthesis of estrogen, metabolism, and exosome, are discussed. Uncovering the roles of adipocytes in the CSC niche will propose novel strategies to treat cancers, especially those whose progression is linked to obesity.

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.

Adipsin alleviates cardiac microvascular injury in diabetic cardiomyopathy through Csk-dependent signaling mechanism.

BACKGROUND: Microvascular complications are associated with an overtly increased risk of adverse outcomes in patients with diabetes including coronary microvascular injury which manifested as disruption of adherens junctions between cardiac microvascular endothelial cells (CMECs). However, particular mechanism leading to diabetic coronary microvascular hyperpermeability remains elusive. METHODS: Experimental diabetes was induced in mice with adipose tissue-specific Adipsin overexpression (AdipsinLSL/LSL-Cre) and their respective control (AdipsinLSL/LSL). In addition, cultured CMECs were subjected to high glucose/palmitic acid (HG + PA) treatment to simulate diabetes for a mechanistic approach. RESULTS: The results showed that Adipsin overexpression significantly reduced cardiac microvascular permeability, preserved coronary microvascular integrity, and increased coronary microvascular density. Adipsin overexpression also attenuated cardiac dysfunction in diabetic mice. E/A ratio, an indicator of cardiac diastolic function, was improved by Adipsin. Adipsin overexpression retarded left ventricular adverse remodeling, enhanced LVEF, and improved cardiac systolic function. Adipsin-enriched exosomes were taken up by CMECs, inhibited CMECs apoptosis, and increased CMECs proliferation under HG + PA treatment. Adipsin-enriched exosomes also accelerated wound healing, rescued cell migration defects, and promoted tube formation in response to HG + PA challenge. Furthermore, Adipsin-enriched exosomes maintained adherens junctions at endothelial cell borders and reversed endothelial hyperpermeability disrupted by HG + PA insult. Mechanistically, Adipsin blocked HG + PA-induced Src phosphorylation (Tyr416), VE-cadherin phosphorylation (Tyr685 and Tyr731), and VE-cadherin internalization, thus maintaining CMECs adherens junctions integrity. LC-MS/MS analysis and co-immunoprecipitation analysis (Co-IP) unveiled Csk as a direct downstream regulator of Adipsin. Csk knockdown increased Src phosphorylation (Tyr416) and VE-cadherin phosphorylation (Tyr685 and Tyr731), while abolishing Adipsin-induced inhibition of VE-cadherin internalization. Furthermore, Csk knockdown counteracted Adipsin-induced protective effects on endothelial hyperpermeability in vitro and endothelial barrier integrity of coronary microvessels in vivo. CONCLUSIONS: Together, these findings favor the vital role of Adipsin in the regulation of CMECs adherens junctions integrity, revealing its promises as a treatment target against diabetic coronary microvascular dysfunction. Graphical abstract depicting the mechanisms of action behind Adipsin-induced regulation of diabetic coronary microvascular dysfunction.

Associations between Adipokines and Metabolic Dysfunction-Associated Fatty Liver Disease Using Three Different Diagnostic Criteria.

BACKGROUND: A panel of experts proposed a new definition of metabolic dysfunction-associated fatty liver disease (MAFLD) in 2020. To date, the associations between adipokines, such as adiponectin, adipsin, and visfatin and MAFLD remain unclear. Therefore, we aimed to evaluate the associations between each of these three adipokines and MAFLD using different diagnostic criteria. METHODS: In total, 221 participants were included in our study based on medical examination. Detailed questionnaire information, physical examination, abdominal ultrasound, and blood-biochemical-test indexes were collected. The levels of adipokines were tested by using an enzyme immunoassay. Logistic regression models were used to assess the associations of the adipokines with MAFLD. RESULTS: In total, 122 of the participants were diagnosed with MAFLD. Higher levels of adipsin and lower levels of adiponectin were found in the MAFLD group than in the non-MAFLD group (all p < 0.05). According to the logistic regression analysis, the ORs were 0.11 (95% CI: 0.05-0.23) for adiponectin, 4.46 (95% CI: 2.19-9.12) for adipsin, and 0.51 (95% CI: 0.27-0.99) for visfatin when comparing the highest tertile with the lowest tertile (all p-trend < 0.05). The inverse association between adiponectin and MAFLD was strongest when T2DM was used as the diagnostic criterion alone, and the positive association between adipsin and MAFLD was strongest when BMI was used as the diagnostic criterion alone. There was no significant association between visfatin and MAFLD, regardless of whether each of BMI, T2DM, or metabolic dysregulation (MD) was used as the diagnostic criterion for MAFLD alone. CONCLUSION: Adipsin levels were positively associated with MAFLD and adiponectin levels were inversely associated with MAFLD. The strength of these associations varied according to the different diagnostic criteria for MAFLD.

Subjective assessment and biochemical evaluation of traction therapy in women with chronic low back pain: does body mass index matter? A clinical study.

BACKGROUND: Apart from the positive effect of lumbar traction on structural changes within the spine in patients with low back pain, it is likely that therapeutic effects are correlated with pain biomarkers in the blood. Among them, systemic metabolic factors related to obesity may play an important role. This is the first study designed to examine the effectiveness of traction therapy in two experimental groups with considerably different BMI and to assess relationships between blood biomarkers and low back pain intensity. METHODS: In the prospective clinical trial, women suffering from chronic low back pain were allocated into the normal-weight or obesity groups. Patients in both groups underwent twenty sessions of lumbar traction therapy (30 min a day, continuous mode with a force level of 25-30% of body weight). Before and after therapy subjective assessments of pain (VAS and PPT) were performed, and serum concentrations of aggrecan chondroitin sulfate 846 epitope (CS-846), neuropeptide Y, leptin, adipsin and growth and differentiation factor 15 (GDF-15) were determined. The data were statistically evaluated for 28 women. RESULTS: After therapy, the maximal low back pain decreased in both groups, GDF-15 concentration was reduced in the normal-weight group and increased in the obesity group, and CS-846 concentration decreased in the obesity group. The sensation of PPT in the lumbar spine and mean concentrations of neuropeptide Y, leptin and adipsin did not change in both groups. However, the relationships of GDF-15, leptin, and adipsin concentrations with the perception of pain were revealed. CONCLUSION: Distinct differences between the normal-weight and obesity groups pointed on the role of excessive adipose tissue in aggravating the inflammatory processes and in the development of low back pain. Adipsin, CS-846 and GDF-15 aspire to be the low back pain biomarkers in women with obesity, but there is a need for further research to answer whether they might be considered reliable biomarkers for the prognosis and monitoring of chronic low back treatment. TRIAL REGISTRATION: NCT04507074, registered prospectively on July 6, 2020.

Increased Serum Adipsin Correlates with MAFLD and Metabolic Risk Abnormalities.

Purpose: A panel of international experts proposed a new definition of fatty liver in 2020, namely metabolic dysfunction-associated fatty liver disease (MAFLD). As an adipokine, adipsin is closely related to metabolic-related diseases. In this study, we aimed to evaluate the relationship among MAFLD, serum adipsin, and metabolic risk abnormalities. Methods: Our study was a cross-sectional study based on the first follow-up of the Guangzhou Nutrition and Health Study (GNHS). A total of 908 patients with hepatic steatosis were involved in our study. Detailed data of patients were collected based upon questionnaire information, physical examination, and blood biochemical test. Results: Among the 908 patients, 789 patients were diagnosed with MAFLD. The levels of serum adipsin in the MAFLD group and non-MAFLD group were (3543.00 (3187.94-3972.50) ng/mL) and (3095.33 (2778.71-3354.77) ng/mL) (P < 0.001), respectively. After adjusting for potential confounders, adipsin levels were found to be associated with MAFLD. The OR was 3.46 (95% CI: 1.57-7.64) for adipsin when comparing subjects in the highest tertile with those in the lowest tertile. With the increase in the number of metabolic risk abnormalities, both the levels of serum adipsin and the proportion of moderate to severe fatty liver increased (all p-trend < 0.001). Conclusion: Increased serum adipsin correlates with MAFLD. Both adipsin levels as well as fatty liver severity increase with higher numbers of metabolic risk abnormalities.

PPARγ Acetylation Orchestrates Adipose Plasticity and Metabolic Rhythms.

Systemic glucose metabolism and insulin activity oscillate in response to diurnal rhythms and nutrient availability with the necessary involvement of adipose tissue to maintain metabolic homeostasis. However, the adipose-intrinsic regulatory mechanism remains elusive. Here, the dynamics of PPARγ acetylation in adipose tissue are shown to orchestrate metabolic oscillation in daily rhythms. Acetylation of PPARγ displays a diurnal rhythm in young healthy mice, with the peak at zeitgeber time 0 (ZT0) and the trough at ZT18. This rhythmic pattern is deranged in pathological conditions such as obesity, aging, and circadian disruption. The adipocyte-specific acetylation-mimetic mutation of PPARγ K293Q (aKQ) restrains adipose plasticity during calorie restriction and diet-induced obesity, associated with proteolysis of a core circadian component BMAL1. Consistently, the rhythmicity in glucose tolerance and insulin sensitivity is altered in aKQ and the complementary PPARγ deacetylation-mimetic K268R/K293R (2KR) mouse models. Furthermore, the PPARγ acetylation-sensitive downstream target adipsin is revealed as a novel diurnal factor that destabilizes BMAL1 and mediates metabolic rhythms. These findings collectively signify that PPARγ acetylation is a hinge connecting adipose plasticity and metabolic rhythms, the two determinants of metabolic health.

Influence of eight weeks of combined training on adipsin and lipoprotein profile and possible relations with depression, anxiety and stress in women with multiple sclerosis.

OBJECTIVES: Immobility and its physiological and psychological consequences are common problems in patients with multiple sclerosis. The aim of this study was to investigate the effect of 8 weeks of combined training on Adipsin and lipid profile and the possible relationship between these indicators and psychological function in women with multiple sclerosis. METHODS: In this quasi-experimental study, 40 women with multiple sclerosis were selected by purposeful sampling method and randomly divided into two equal control and exercise groups (n=20). Exercise was performed for 8 weeks (two resistance sessions and one endurance session per week). Before and after the intervention, blood samples were taken and the DASS-21 questionnaire was completed to assess anxiety, depression and stress. Data were analyzed using analysis of covariance, t-test, Bonferroni post hoc test and Pearson correlation test at a significance level of p≤0.05. RESULTS: In the exercise group, levels of Adipsin, total cholesterol, LDL, TG, weight, fat percentage, WHR, BMI, depression, anxiety and stress were significantly reduced and HDL levels were significantly increased after 8 weeks of combined exercise (p≤0.05). Also, BMI (p=0.01), fat percentage (p=0.01) and WHR (p=0.01) levels had significant positive correlation with Adipsin. There was a significant positive relationship between Total cholesterol level with depression index (p=0.04). CONCLUSIONS: Performing combination exercises through improving body composition can increase the risk of obesity and cardiovascular risk factors and improve the psychological function of patients with multiple sclerosis. Specialists can use these exercises as an adjunct to drug therapy for MS patients.

Exosomes derived from pericardial adipose tissues attenuate cardiac remodeling following myocardial infarction by Adipsin-regulated iron homeostasis.

As a vital adipokine, Adipsin is closely associated with cardiovascular risks. Nevertheless, its role in the onset and development of cardiovascular diseases remains elusive. This study was designed to examine the effect of Adipsin on survival, cardiac dysfunction and adverse remodeling in the face of myocardial infarction (MI) injury. In vitro experiments were conducted to evaluate the effects of Adipsin on cardiomyocyte function in the face of hypoxic challenge and the mechanisms involved. Our results showed that Adipsin dramatically altered expression of proteins associated with iron metabolism and ferroptosis. In vivo results demonstrated that Adipsin upregulated levels of Ferritin Heavy Chain (FTH) while downregulating that of Transferrin Receptor (TFRC) in peri-infarct regions 1 month following MI. Adipsin also relieved post-MI-associated lipid oxidative stress as evidenced by decreased expression of COX2 and increased GPX4 level. Co-immunoprecipitation and immunofluorescence imaging prove a direct interaction between Adipsin and IRP2. As expected, cardioprotection provided by Adipsin depends on the key molecule of IRP2. These findings revealed that Adipsin could be efficiently delivered to the heart by exosomes derived from pericardial adipose tissues. In addition, Adipsin interacted with IRP2 to protect cardiomyocytes against ferroptosis and maintain iron homeostasis. Therefore, Adipsin-overexpressed exosomes derived from pericardial adipose tissues may be a promising therapeutic strategy to prevent adverse cardiac remodeling following ischemic heart injury.

Inhibition of macrophage-derived foam cells by Adipsin attenuates progression of atherosclerosis.

Phagocytosis of oxidized low-density lipoprotein (OxLDL) by macrophages yields "foam cells" and serves as a hallmark of atherosclerotic lesion. Adipsin is a critical component of the complement activation pathway. Recent evidence has indicated an obligatory role for Adipsin in pathological models including ischemia-reperfusion and sepsis. Adipsin levels are significantly decreased in patients with asymptomatic carotid atherosclerosis, implying the role for Adipsin as a potential marker of asymptomatic carotid atherosclerosis. This study was designed to evaluate the role for Adipsin in atherosclerosis and the mechanisms involved using both in vivo and in vitro experiments. ApoE-/-/AdipsinTg mice were constructed and were fed a high-fat diet for 12 weeks. Compared with ApoE-/- mice, area of the sclerotic plaques was reduced, along with lower macrophage deposition within the plaque in ApoE-/-/AdipsinTg mice. RAW264.7 cells and bone marrow-derived macrophages (BMDMs) were stimulated with oxLDL (50 µg/ml). Adenovirus vectors containing the Adipsin gene were transfected into macrophages. Lipid accumulation was observed by Oil red O staining. Western blot and reverse transcription-polymerase chain reaction data revealed that Adipsin overexpression inhibited oxLDL-induced lipid uptake and foam cell formation and upregulation of CD36 and PPARγ in Ad-Adipsin-transfected macrophages. In addition, the PPARγ-specific agonist GW1929 reversed Adipsin overexpression-evoked inhibitory effect on lipid uptake. These results demonstrate unequivocally that Adipsin inhibits lipid uptake in a PPARγ/CD36-dependent manner and prevents the formation of foam cells, implying that Adipsin may be a potential therapeutic target against atherosclerosis.

Elevated Adipsin and Reduced C5a Levels in the Maternal Serum and Follicular Fluid During Implantation Are Associated With Successful Pregnancy in Obese Women.

Introduction: Complement factors mediate the recruitment and activation of immune cells and are associated with metabolic changes during pregnancy. The aim of this study was to determine whether complement factors in the maternal serum and follicular fluid (FF) are associated with in vitro fertilization (IVF) outcomes in overweight/obese women. Methods: Forty overweight/obese (BMI = 30.8 ± 5.2 kg/m2) female patients, 33.6 ± 6.3 years old, undergoing IVF treatment for unexplained infertility were recruited. Baseline demographic information, including biochemical hormonal, metabolic, and inflammatory markers, and pregnancy outcome, was collected. Levels of 14 complement markers (C2, C4b, C5, C5a, C9, adipsin, mannose-binding lectin, C1q, C3, C3b/iC3b, C4, factor B, factor H, and properdin) were assessed in the serum and FF and compared to IVF outcome, inflammatory, and metabolic markers using multivariate and univariate models. Results: Out of 40 IVF cycles, 14 (35%) resulted in pregnancy. Compared to women with failed pregnancies, women with successful pregnancies had higher levels of adipsin in the serum and FF (p = 0.01) but lower C5a levels (p = 0.05). Serum adipsin levels were positively correlated with circulating levels of vitamin D (R = 0.5, p = 0.02), glucagon (R = 0.4, p = 0.03), leptin (R = 0.4, p = 0.01), resistin (R = 0.4, p = 0.02), and visfatin (R = 0.4, p = 0.02), but negatively correlated with total protein (R = -0.5, p = 0.03). Higher numbers of top-quality embryos were associated with increased levels of C3, properdin, C1q, factors H and B, C4, and adipsin, but with reduced C2 and C5a levels (p ≤ 0.01). Conclusions: Higher adipsin and lower C5a levels in the maternal serum during implantation are potential markers of successful outcome in obese women undergoing IVF-assisted pregnancies.

Evaluation of Applicability of Novel Markers of Metabolic Syndrome in Adult Men.

There is a continuous worldwide increase in incidences of metabolic syndrome (MetS) reaching about a quarter of the world's population. Thus, studies that allow for a robust diagnosis of MetS are of paramount importance from an economic and medical point of view. This study was carried out in a group of men diagnosed with MetS using consensus definition criteria that included the definitions of the International Diabetes Foundation and Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute. The control group consisted of men for whom the parameters that define the MetS were in the norm. This study analyzed statistical differences between MetS and healthy men and the correlations between the set of 14 potential markers of MetS, that is, between body mass index, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein, triglycerides, cortisol, adiponectin, monocyte chemotactic protein-1 (MCP-1), C-reactive protein (CRP), adipsin, leptin, resistin, and plasminogen activator inhibitor-1 (PAI)-1. This report revealed a significant difference between MetS and healthy men in most of the parameters studied. Furthermore, a strong positive correlation between cortisol levels and body mass index was demonstrated. Furthermore, MCP-1 levels in men with MetS were significantly higher than their levels in healthy men. Finally, a strong positive correlation was also observed between adiponectin and adipsin in Mets men. Thus, this study reveals the potential usefulness of adiponectin, MCP-1, adipsin, leptin, resistin, and PAI-1 as markers of MetS in adult men.

Quantification of the pro-form of human complement component factor D (adipsin).

Factor D (also known as adipsin) is a serine protease and part of the complement system, involved in innate immune responses and effector functions of antibodies. Factor D cleaves factor B complexed with C3b, leading to the C3 convertase C3bBb. This C3 convertase is central in the alternative activation pathway and the amplification loop, which amplifies the two other complement activation pathways: the classical pathway and the lectin pathway. Adipocytes synthesize factor D as a pro-form comprising 6 additional residues that must be cleaved off to generate a mature form. The MBL-associated serine protease 3 (MASP-3), found in complex with the pattern recognition molecules of lectin activation pathway, converts the pro-form to mature factor D, which reportedly is the most abundant form found in the circulation at concentrations of 1-2 µg/ml among healthy individuals. The mature factor D is rate-limiting for complement activation, but little is known about the distribution of pro vs. mature factor D in the circulation, the regulation hereof and the potential activation stimuli of the lectin pathway, responsible for activation of MASP-3 and subsequent conversion of pro-form of factor D. In this light we established and validated an ELISA specific for measuring the pro-form of complement factor D. With a working range of 0.82-25 ng/ml, acceptable intra and inter assay CVs, and a relative recovery rate above 90%, we found that the median plasma concentration in Danish blood donors was 134 ng/ml; corresponding to that 8-15% factor D circulates as pro-form. We also found that blood sampling procedures affect conversion and hence the levels measured in serum and plasma.

Stachydrine derived from fermented rice prevents diet-induced obesity by regulating adipsin and endoplasmic reticulum homeostasis.

Makgeolli, a widely consumed traditional alcoholic beverage in Korea, is brewed mainly from rice using Nuruk as a fermentation starter, which contains fungi, yeast, and lactic acid bacteria. Among 58 Makgeolli samples brewed using various Nuruks, we found that one exhibited anti-obesity properties, with stachydrine shown to be responsible for these properties. Stachydrine promotes lipolysis and inhibits lipid accumulation in 3T3-L1 adipocytes; it also reduces weight gain and improves glucose tolerance and insulin resistance in a mouse model. Stachydrine dramatically suppresses adipsin mRNA levels in liver and adipose tissue, whereas serum adipsin levels were elevated in stachydrine-treated mice compared to mice fed a high-fat diet alone. Moreover, stachydrine recovers endoplasmic reticulum homeostasis and regulates adipsin expression. We highlight the potential use of stachydrine as a therapeutic agent for the treatment of obesity and insulin resistance and the use of Makgeolli fermented by Nuruk as a source of novel bioactive compounds.

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.