Sensitive asprosin detection in clinical samples reveals serum/saliva correlation and indicates cartilage as source for serum asprosin.

The C-terminal pro-fibrillin-1 propeptide asprosin is described as white adipose tissue derived hormone that stimulates rapid hepatic glucose release and activates hunger-promoting hypothalamic neurons. Numerous studies proposed correlations of asprosin levels with clinical parameters. However, the enormous variability of reported serum and plasma asprosin levels illustrates the need for sensitive and reliable detection methods in clinical samples. Here we report on newly developed biochemical methods for asprosin concentration and detection in several body fluids including serum, plasma, saliva, breast milk, and urine. Since we found that glycosylation impacts human asprosin detection we analyzed its glycosylation profile. Employing a new sandwich ELISA revealed that serum and saliva asprosin correlate strongly, depend on biological sex, and feeding status. To investigate the contribution of connective tissue-derived asprosin to serum levels we screened two cohorts with described cartilage turnover. Serum asprosin correlated with COMP, a marker for cartilage degradation upon running exercise and after total hip replacement surgery. This together with our finding that asprosin is produced by primary human chondrocytes and expressed in human cartilage suggests a contribution of cartilage to serum asprosin. Furthermore, we determined asprosin levels in breast milk, and urine, for the first time, and propose saliva asprosin as an accessible clinical marker for future studies.

The modulatory effects of irisin on asprosin, leptin, glucose levels and lipid profile in healthy and obese male and female rats.

OBJECTIVES: The main aim of this study was to investigate the effects of irisin on asprosin, leptin, glucose levels and lipid profile in healthy and obese male and female rats. METHODS: Irisin was subcutaneously administered with osmotic minipumps at the dose of 100 ng/kg/day for 28 days and then, the serum levels of asprosin, leptin, glucose and lipid profile were investigated. RESULTS: Irisin infusion increased asprosin levels in male rats (p = .02) but not in female rats. Irisin inhibited obesity-induced high glucose, low-density lipoprotein (LDL), triglyceride (TG) and leptin levels in all groups; however, it did not lead to any change in asprosin levels in both obese female and male rats. CONCLUSIONS: It was determined that irisin increased serum asprosin levels and decreased LDL, TG, glucose and leptin levels, and this could indicate a protective role of irisin against obesity development.

Serum levels of Asprosin in patients diagnosed with coronary artery disease (CAD): a case-control study.

BACKGROUND: Coronary artery disease (CAD) is considered as a multi-faceted chronic inflammatory disease involving reduced blood supply to the myocardium as a result of accumulating lipids in the atrial walls. Visceral adiposity with disrupted release of adipokines play a key role in its pathogenesis. Asprosin is a newly identified fasting-induced glucogenic adipokine that has been related with metabolic disorders such as type II diabetes mellitus and polycystic ovary syndrome. The preset study sought to assess circulating asprosin in context of CAD. METHODS: In this study, serum levels of asprosin were determined in 88 CAD patients and 88 non-CAD healthy controls. Serum IL-6, TNF-α, asprosin and adiponectin were assessed using ELISA kits. RESULTS: Serum asprosin was found to be higher in CAD patients when compared to non-CAD subjects (7.84 ± 2.08 versus 5.02 ± 1.29 µg/mL, p <  0.001). Similarly, serum TNF-α, and IL-6 elevated in CAD group significantly (p <  0.001). However, circulating adiponectin diminished in CAD group when compared with non-CAD subjects (p < 0.001). Moreover, serum asprosin levels directly correlated with BMI, FBG, HOMA-IR, TG and TC. Logistic regression analyses showed that asprosin levels were associated with increased risk of developing CAD (odds ratio: 3.01, 95% CI: 2.16, 4.20 and p < 0.001), after adjusting for potential confounders (age, sex and BMI). CONCLUSIONS: The present study findings suggested a possible relation of serum asprosin with the pathogenesis of CAD, in particular through insulin resistance and dyslipidemia.

Plasma asprosin, CCDC80 and ANGPTL4 levels are associated with metabolic and cardiovascular risk in patients with inflammatory bowel disease.

Asprosin, coiled-coil domain-containing 80(CCDC80) and angiopoietin-like4(ANGPTL4) are newly discovered adipocytokine that affects glucose tolerance, insulin resistance and cardiovascular diseases. The goal of this study was to investigate if a relationship exists among asprosin, CCDC80 and ANGPTL4 and inflammatory bowel disease (IBD). Fifty subjects with newly diagnosed IBD and fifty healthy individuals were enrolled. Patients were treated with standard therapies for 3 months. Plasma asprosin, CCDC80 and ANGPTL4 levels were measured with enzyme-linked immunosorbent assay. High resolution ultrasound was used to measure brachial artery diameter at rest, after reactive hyperemia (flow-mediated dilation, FMD) and after sublingual glyceryltrinitrate.Compare with healthy individuals, plasma CCDC80,erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels and homeostasis modelassessment of insulin resistance (HOMA-IR) were significantly higher (p < 0.05, respectively), whereas plasma asprosin,ANGPTL4 levels and FMD were significantly lower inboth UC and CD patients(p <0.05). Plasma CCDC80 levels were significantly higher in patients with CD (p<0.05), while plasma asprosin and ANGPTL4 levels were lower (p<0.05) as compared with those in patients with UC. Standard therapies increased plasma asprosin, ANGPTL4 levels and FMD in both UC and CD (p<0.05),UC and CD patientswhile decreased plasma CCDC80, ESR, CRP levels and HOMA-IR (p<0.05). The changes in HOMA-IR and FMD were correlated with the changes in plasma asprosin, CCDC80 and ANGPTL4 levels over the study period (p<0.05). Plasma asprosin, CCDC80 and ANGPTL4 levels may be applied as a significant marker for early stage of insulin resistance and atherosclerosis in IBD, especially of CD.

Subfatin and asprosin, two new metabolic players of polycystic ovary syndrome.

Asprosin and subfatin are recently discovered two new hormones of adipocyte origin that play a role in the regulation of glucose metabolism. Polycystic ovary syndrome (PCOS) is a gynaecological syndrome presenting with energy turbulence. The aim of this study was to investigate whether asprosin and subfatin play a role in PCOS disease. Thirty participants with a diagnosis of PCOS and thirty control group participants were included in this case-control study. Hormone profiles of the participants (subfatin, asprosin, insulin, prolactin, thyroid-stimulating hormone (TSH), oestradiol (E2), follicle-stimulating hormone (FSH), luteinising hormone (LH), dehydroepiandrosterone sulphate (DHEA-SO4), lipid profiles [(total testosterone, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride, cholesterol)], fasting blood sugar (FBS) and high-sensitivity C-reactive protein (hs-CRP) values were measured. While the levels of asprosin, LDL and triglyceride, TSH, E2, FSH, LH, DHEA-SO4 were found to be significantly higher in patients with PCOS compared to controls (p = .005; p = .01), subfatin and HDL levels were found to be low. Significantly decreasing subfatin and increasing asprosin levels in circulation in PCOS may play a role in the etiopathology of this disease and that they may also be new candidate molecules in addition to classical laboratory parameters in the diagnosis and follow-up of PCOS in the future.Impact statementWhat is already known on this subject? The studies investigating the relationship between PCOS and asprosin are contradictory. Although subfatin has been studied in many metabolic diseases, it has not been studied yet whether it is associated with PCOS. Furthermore, whether there is a mutual relationship between subfatin and asprosin in patients with PCOS has not been studied yet.What do the results of this study add? This available data indicates that significantly decreasing subfatin and increasing asprosin levels in the circulation in PCOS may play a role in the etiopathology of this disease.What are the implications of these findings for clinical practice and/or further research? The findings are promising in that decreasing subfatin and increasing asprosin levels will shed new light on reproductive endocrinology changes caused by PCOS and may help to clarify the pathophysiology of PCOS. Furthermore, in our study, the asprosin/subfatin ratio was above three in PCOS disease. This ratio reported here is anticipated to contribute to the course or follow-up of the disease in the future. Also, subfatin has been investigated here for the first time, may also be a new candidate molecule in addition to classical laboratory parameters in the diagnosis and follow-up of PCOS.

Fasted plasma asprosin concentrations are associated with menstrual cycle phase, oral contraceptive use and training status in healthy women.

PURPOSE: Asprosin, an orexigenic hormone that stimulates hepatic glucose release, is elevated in insulin resistance and associated with obesity. Plasma asprosin concentrations may also be related to female sex hormone levels; higher levels are reported in women with polycystic ovary syndrome (PCOS) but this may be related to peripheral insulin resistance also associated with PCOS. Clarification of female-specific factors influence on the plasma asprosin response is crucial for studies investigating asprosin. Therefore, this study determined the association of menstrual phase, oral contraceptive (OC) use (as a pharmacological influence on sex hormone levels) and training status (as a physiological influence on sex hormone levels) on plasma asprosin levels in pre-menopausal women. METHODS: Fasting plasma asprosin, 17ß-estradiol (E2) and progesterone, were assessed in 32 healthy untrained and trained women with regular menstrual cycles (non-OC; n = 8 untrained, n = 6 trained) or using OC (n = 10 untrained, n = 8 trained) during early follicular, late follicular and mid-luteal menstrual phases (or the time-period equivalent for OC users). RESULTS: Asprosin was lower in OC (0.75 ± 0.38 ng mL-1) than non-OC users (1.00 ± 0.37 ng mL-1; p = 0.022). Across a cycle, asprosin was highest in the early follicular equivalent time-point in OC users (0.87 ± 0.37 ng mL-1) but highest in the mid-luteal phase in non-OC users (1.09 ± 0.40 ng mL-1). Asprosin concentrations varied more across a cycle in untrained than trained women, with higher concentrations in the early follicular phase compared to the late follicular and mid-luteal (training status-by-menstrual phase interaction p = 0.028). CONCLUSION: These findings highlight the importance of considering OC use, menstrual cycle phase and to a lesser extent training status when investigating circulating asprosin concentrations in females.

Expression of asprosin in rat hepatic, renal, heart, gastric, testicular and brain tissues and its changes in a streptozotocin-induced diabetes mellitus model.

In this study, we aimed to investigate the presence of asprosin (ASP) in the liver, kidneys, heart, stomach, testicles and brain and to determine the serum and tissue asprosin levels in diabetic rats. A total of 14 male Wistar Albino rats were divided into two groups, each containing 7 rats: (I) control group and (II) experimental diabetes group. Control rats received no treatment and the rats in the experiment group received single-dose of streptozotocin (STZ) (50 mg/kg) dissolved in 0.1 M sodium citrate buffer (pH: 4.5) intraperitoneally. Serum levels of asprosin were measured using ELISA method. The presence of asprosin in hepatic, renal, cardiac, gastric, testicular and brain tissues was investigated using immunohistochemical staining. Asprosin was detected in hepatocytes in the liver, cortical distal tubule cells in the kidney, cardiomyocytes in heart, surface epithelial cells of stomach fundus, interstitial Leydig cells in testes and cortical neurons of the brain. Compared to control group, it was found that diabetic rats had decreased asprosin levels in liver, kidney and heart tissues, increased levels in gastric and testicular tissues and no significant changes in brain tissue. Serum asprosin levels of diabetic rats were found to be decreased compared to the control group. This is the first study in the literature that reports the presence of asprosin in liver, kidney, heart, stomach, testis and brain tissues in rats. The aim of the study is to determine the presence of ASP, a newly discovered adipokine, in various tissues and to examine tissue and serum level changes in STZ-induced diabetes.

Circulating asprosin levels are increased in patients with type 2 diabetes and associated with early-stage diabetic kidney disease.

PURPOSE: Asprosin was a newly identified secreted hormone which could induce hepatic glucose release. Since asprosin closely associated with the risk factors of diabetic kidney disease (DKD), including hyperglycemia, insulin resistance and inflammation, the present study aimed to investigate the relationship between circulating asprosin levels and the early stage of DKD. METHODS: 30 subjects with normal glucose tolerance (NGT), 42 type 2 diabetes (T2DM) patients without DKD and 33 T2DM patients with early stage of DKD were recruited. Early stage of DKD was defined as two consecutive measurements of urinary albumin-to-creatinine ratio (UACR) 30-299 mg/g and estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m2. Multiple linear regression analysis was conducted to explore the associations of circulating asprosin levels with eGFR and UACR. Multiple logistic regression analysis was used to determine the association of circulating asprosin levels with the early stage of DKD. RESULTS: Circulating asprosin levels in Non-DKD and DKD groups were significantly higher than that in NGT group and the DKD group showed the highest levels. Circulating asprosin levels negatively correlated with eGFR (r = - 0.311, P = 0.007) and positively correlated with UACR (r = 0.345, P = 0.002) in T2DM patients. Even after multivariable adjustment, circulating asprosin levels were closely associated with eGFR and UACR and significantly increased ORs for early stage of DKD (OR = 3.973, P = 0.001). CONCLUSION: Circulating asprosin levels were increased in T2DM and associated with the early stage of DKD. The specific role of asprosin in DKD needs further investigation.

Increased serum circulating asprosin levels in children with obesity.

BACKGROUND: Childhood obesity is a growing and significant problem worldwide. Asprosin is a novel adipokine that is significantly associated with glucose and insulin production in the liver during fasting. In the present study, we aimed to demonstrate whether there would be differences between obese, overweight, and normal weight children in terms of serum asprosin levels. METHODS: Forty-four children with obesity, 54 overweight children, and 60 normal weight children were compared in terms of serum asprosin levels and other anthropometric, biochemical, and hormonal parameters that are associated with being overweight and with obesity. RESULTS: Serum asprosin levels were found to be significantly different between groups: 70.903 ± 17.49 ng/mL, 79.744 ± 29.54 ng/mL, and 106.293 ± 122.69 ng/mL in normal weight, overweight, and obese children respectively. Post-hoc analysis revealed that the asprosin level was significantly higher in obese children compared with normal weight children (P = 0.009). Additionally, asprosin was found to be a predictor of obesity in multiple regression analysis. CONCLUSION: Our study is the first to demonstrate increased levels of asprosin in obese children compared with normal weight children. Further studies are needed to demonstrate the role of asprosin in the etiology of childhood obesity, as well as other diseases that might be associated with effects of asprosin.

The effect of thyroid dysfunction and treatment on adropin, asprosin and preptin levels in rats.

OBJECTIVES: Thyroid hormones have important roles in normal development and energy regulating mechanisms as well as signaling mechanisms that affect energy consumption through central and peripheral pathways. The aim of this study was to determine the effects of thyroid dysfunction on adropin, asprosin and preptin levels in rat. METHODS: The study was performed on the 38 male Wistar-albino rats. Experiment groups were designed as follows. 1-Control, 2-Hypothyroidism; To induce hypothyroidism PTU was applied by intraperitoneal as 10 mg/kg/day for 2 weeks. 3-Hypothyroidism + Thyroxine; Previously animals were made with hypothyroidism by 1 week PTU application and then 1 week l-thyroxine was given by intraperitoneal as 1.5 mg/kg/day. 4-Hyperthyroidism; Rats were made with hyperthyroidism by 3 weeks l-thyroxine (0.3 mg/kg/day). 5-Hyperthyroidism + PTU; Animals were made hyperthyroisim by l-thyroxine as groups 4, then 1 week PTU was applied to treatment of hiperthyrodism. At the end of supplementation animals were sacrificed and blood samples were collected for FT3, FT4, adropin, asprosin, preptin analysis. RESULTS: FT3 ve FT4 levels were reduced significantly in hypothyroidism while increased in hyperthyroidism (p<0.001). Hipothyrodism led to reduces adropin, asprosin and preptin levels. And also hyperthyroidism reduced adropin and preptin levels (p<0.001). CONCLUSIONS: The results of study show that experimental hypothyroidism and hyperthyroidism lead to significantly change to adropin, asprosin and preptin levels. However, correction of thyroid function caused to normals levels in asprosin and preptin.