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Objective: Prediabetes mellitus, hypertension, and their frequent coexistence are risk factors for macrovascular and cardiovascular complications. In this study we aimed to determine the relationship between spexin levels and echocardiographic findings and hypertension in prediabetic patients., Methods: This study included 118 adult patients diagnosed with prediabetes mellitus who presented to outpatient clinics between April 2021 and January 2022. The patients were grouped into prediabetic patients with hypertension (n = 58) and those without hypertension (n = 60). The hypertension group was further divided into dipper and non-dipper groups according to the 24-hour ambulatory blood pressure monitoring. Blood samples were collected from all patients and echocardiography was performed. Spexin levels were measured by ELISA. Serum spexin levels, echocardiographic and ambulatory blood pressure monitoring findings were compared between the groups., Results: The hypertension and non-dipper groups had significantly lower spexin levels and higher left atrial volume index, E/Em index, and interventricular septum and posterior wall thicknesses. Spexin levels were negatively correlated with body mass index (r = -0.298, P < 0.001), nighttime systolic blood pressure (r = -0.264, P = 0.006), nighttime diastolic blood pressure (r =-.255, P = 0.005), left atrial volume index (r =-.238, P = 0.009), E/Em (r =-.214,P = 0.020), and low-density lipoprotein cholesterol (r = -.243, P = 0.008). Obesity, overweight and spexin <780 pg/mL were independently associated with hypertension., Conclusion: Circulating spexin levels were lower in prediabetic patients with overall hypertension and in non-dipper patients, and were associated with echocardiographic and lipid parameters. The cut-off value of spexin identified in our study may be a useful indicator for hypertension detection and raise clinicians' awareness about evaluating prediabetic patients for hypertension.

Hormones are specific molecules measured in biological fluids by elaborate analytical systems requiring meticulous attention. Variation between laboratories can be expected. However, recently published measurements of AVP, OXT, and BNP in human plasma under basal/control conditions include numbers which, between publications, vary by 100-10 000-fold. Generally, the methods descriptions are scant, at best, and provide no information about quality control measures. Clearly, two results describing the same basal hormone concentration by numbers three orders of magnitude apart are incongruent providing reason for concern. Basal concentrations of bioactive AVP, OXT, and BNP in human plasma are in the order of 1-10 pmol/L. Therefore, assay systems applied to plasma must be able to measure concentrations of less than 1 pmol/L with appropriate specificity and accuracy. Basal concentrations of AVP, OXT, and BNP above 100 pmol/L should be reconsidered, as such results do not reflect bioactive hormone levels in humans, rats, or mice. Any concentration above 1000 pmol/L is of concern because such levels of bioactive hormone may be seen only under extreme conditions, if at all., (© 2024 The Author(s). Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.)

We investigated the effects of tobacco smoke exposure and abnormal body weight on selected peptide hormones and their association with metabolic and hormonal disorders in women with polycystic ovary syndrome (PCOS). The study group included 88 women with PCOS and 28 women without the disease. In women with PCOS, chemerin, lipocalin, and apelin concentrations were influenced by overweight and obesity status, with the highest concentrations observed in those with a body mass index (BMI) ≥ 30.0. Exposure to tobacco smoke significantly increased only lipocalin-2 concentration. The disease itself did not affect the concentrations of chemerin, lipocalin, and apelin. Additionally, we found a positive correlation between chemerin concentration and fasting glucose, fasting insulin, and triglycerides levels, while a negative correlation was observed with high-density lipoprotein (HDL-C) concentration. In the smoking subgroup, chemerin concentration was positively correlated with free testosterone concentration and the free androgen index and negatively associated with sex hormone-binding globulin concentration. Our findings indicate that abnormal body weight has a stronger impact than tobacco smoke exposure on metabolic and hormonal disorders in women with PCOS, highlighting the important role of weight control in such individuals. However, smoking appears to be an additional factor that intensifies hormonal disorders associated with adipose tissue.

Background: Diabetic kidney disease (DKD) is one of the most serious microvascular complications of diabetes mellitus (DM) and the leading cause of chronic kidney disease (CKD) worldwide. Since obesity and type 2 DM (T2DM) are considered as inflammatory conditions, thus reducing their accompanied systemic inflammation may lessen their complications. Sestrin 2 belongs to a group of stress induced proteins which are produced in response to oxidative stress, inflammation and DNA damage. Betatrophin; a hormone that stimulates the growth, proliferation and mass expansion of pancreatic beta-cells and improves glucose tolerance. The objective of the study was to evaluate levels of serum Sestrin 2 and betatrophin in patients with different stages of diabetic nephropathy (DN)) and compare results with healthy control., Methods: This cross sectional study was carried out on 60 patients above 18 years old, recruited from Tanta University hospitals out patients clinics and 20 apparently healthy individuals of matched sex and age as a control group. Participants were divided into two groups: group I: 20 normal subjects as control group and group II: 60 patients with type 2 DM,. further subdivided in to three equal groups: group 1IIA(20 patients) with normo-albuminuria (ACR < 30 mg/g), group IIB (20 patients) with micro albuminuria (ACR = 30 to 300 mg/g) and group IIC (20 patients) with macro albuminuria (ACR > 300 mg/g). They were subjected to detailed history taking, careful clinical examination and laboratory investigations including blood urea, serum creatinine, estimated glomerular filtration rate (eGFR), urinary albumin creatinine ratio, and specific laboratory tests for Sestrin 2 and Betatrophin by using ELISA technique., Results: Serum Sestrin 2 significantly decreased, while serum betatrophin level significantly increased in macroalbuminuric group compared to control and other 2 diabetic groups (P value < 0.05). The cut off value of serum sestrin 2 was 0.98 ng/ml with sensitivity 99%, specificity 66% while the cut off value of serum betatrophin was > 98.25 ng/ml with sensitivity 98%, specificity 82%. Serum betatrophin positively correlated with age, fasting, 2 h postprandial, BMI, triglyceride, total cholesterol, serum creatinine, blood urea, UACR, and negatively correlated with eGFR and serum albumin. Serum Sestrin 2 positively correlated with serum albumin. BMI, serum urea, UACR and serum albumin. Serum betatrophin are found to be risk factors or predictors for diabetic nephropathy., Conclusions: Patients with DN, particularly the macroalbuminuria group, had a significant increase in betatrophin levels and a significant decrease in serum Sestrin 2 level. The function of Sestrin 2 is compromised in DN, and restoring it can reverse a series of molecular alterations with subsequent improvement of the renal functions, albuminuria and structural damage., (© 2024. The Author(s).)

Patients with schizophrenia show a disproportionally increased risk of cardiovascular disease. Hypertriglyceridemia is prevalent in this population; however, how this relates to levels of remnant cholesterol, triglyceride (TG)-rich lipoprotein (TRL) particle size and composition, TG turnover, and apolipoprotein (apo) and angiopoietin-like protein (ANGPTL) concentrations is unknown. Fasting levels of cholesterol (total [TC], LDL-C, HDL-C, non-HDL-C and remnant cholesterol) and TG were determined in 110 patients diagnosed with schizophrenia, and 46 healthy controls. TRL particle size, concentration and composition, and β-hydroxybutyrate (TG turnover marker) were assessed by NMR. Levels of apoCII, apoCIII, apoE, ANGPTL3, ANGPTL4, and ANGPTL8 were measured by ELISA, and apoCII, apoCIII and apoE were further evaluated in HDL and non-HDL fractions. Patients with schizophrenia had significantly elevated TG, TG:apoB ratio, non-HDL-C, remnant cholesterol, non-HDL-apoCII and non-HDL-apoCIII, and HDL-apoE (all P < 0.05), lower HDL-C and apoA-I (all P < 0.001), and comparable apoB, TC, TC:apoB ratio, LDL-C, β-hydroxybutyrate, ANGPTL3, ANGPTL4 and ANGPTL8 to healthy controls. Patients had a 12.0- and 2.5-fold increase in the concentration of large and medium TRL particles respectively, but similar cholesterol:TG ratio within each particle. Plasma TG, remnant cholesterol, and large and medium TRL particle concentrations correlated strongly with apoCII, apoCIII, and apoE in the non-HDL fraction, and with apoCIII and apoE in the HDL fraction in patients with schizophrenia. Differences in TG, HDL-C, TRL particle concentrations, apoCIII, and apoE persisted after adjustment for conventional risk factors. These results are consistent with impaired TRL lipolysis and clearance in patients with schizophrenia which may be responsive to targeting apoCIII., Competing Interests: Conflict of interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: L.K. has participated in clinical trials sponsored by Amgen and Novartis; he has given lectures and received consulting fees from Seqiris (CSL), Amgen and Novartis. D.S. has participated in clinical trials sponsored by NHMRC Clinical Trials Centre; he has received support from Arrowhead Pharmaceuticals for previous publications; he has received grants/contracts sponsored by Regeneron Pharmaceuticals, Ionis Pharmaceuticals, Arrowhead Pharmaceuticals, Amgen and Novartis; he has given lectures and received consulting fees from Amgen and Novartis; he has received contributions from Sanofi., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Spexin (SPX) is a 14-amino-acid peptide that plays an important role in the regulation of metabolism and energy homeostasis. It is well known that a variety of bioactive molecules released into the circulation by organs and tissues in response to acute and chronic exercise, known as exerkines, mediate the benefits of exercise by improving metabolic health. However, it is unclear whether acute exercise affects SPX levels in the circulation and peripheral tissues. This study aimed to determine whether acute treadmill exercise induces plasma SPX levels, as well as mRNA expression and immunostaining of SPX in skeletal muscle, adipose tissue, and liver. Male Sprague Dawley rats were divided into sedentary and acute exercise groups. Plasma, soleus (SOL), extensor digitorum longus (EDL), adipose tissue, and liver samples were collected at six time points (0, 1, 3, 6, 12, and 24 h) following 60 min of acute treadmill exercise at a speed of 25 m/min and 0 % grade. Acute exercise increased plasma SPX levels and induced mRNA expression of Spx in the SOL, EDL, and liver. Immunohistochemical analysis demonstrated that acute exercise led to a decrease in SPX immunostaining in the liver. Taken together, these findings suggest that SPX increases in response to acute exercise as a potential exerkine candidate, and the liver may be one of the sources of acute exercise-induced plasma SPX levels in rats. However, a comprehensive analysis is needed to fully elucidate the systemic response of SPX to acute exercise, as well as the tissue from which SPX is secreted., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Spexin is a novel peptide hormone and has shown antinociceptive effects in experimental mice. This study is aimed at evaluating the association of serum spexin level with diabetic peripheral neuropathy (DPN) and related pain in a Chinese population. Methods: We enrolled 167 type 2 diabetes mellitus (T2DM) including 56 patients without DPN (non-DPN), 67 painless DPN, and 44 painful DPN. Serum spexin was measured using ELISA. Logistic regression models were performed to analyze the independent effects of spexin on prevalence of DPN and painful DPN. In streptozotocin (STZ)-induced diabetic mice, mechanical pain threshold was measured using electronic von Frey aesthesiometer. Human peripheral blood mononuclear cells (PBMCs) were isolated and further stimulated with lipopolysaccharide without or with spexin. The gene expression was assayed by qPCR. Results: Compared with non-DPN, serum spexin level decreased in painless DPN and further decreased in painful DPN. The odds of DPN was associated with low spexin level in T2DM, which was similar by age, sex, BMI, and diabetes duration, but attenuated in smokers. The odds of having pain was associated with decreased spexin level in DPN, which was similar by age, sex, smoking status, and diabetes duration, but attenuated in normal weight. Furthermore, we observed that mechanical pain threshold increased in spexin-treated diabetic mice. We also found that lipopolysaccharide treatment increased the mRNA level of TNF- α , IL-6, and MCP-1 in human PBMCs, while spexin treatment prevented this increase. Conclusions: These results suggested that spexin might serve as a protective factor for diabetes against neuropathology and pain-related pathogenesis., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Ying Liu et al.)

The predictive power of B-type natriuretic peptide (BNP) and left ventricular ejection fraction (LVEF) is limited by its low specificity in patients with heart failure (HF). Discovery of more novel biomarkers for HF better diagnosis is necessary and urgent. ELABELA, an early endogenous ligand for the G protein-coupled receptor APJ (Apelin peptide jejunum, Apelin receptor), exhibits cardioprotective actions. However, the relationship between plasma ELABELA and cardiac function in HF patients is unclear. To evaluate plasma ELABELA level and its diagnostic value in HF patients, a total of 335 patients with or without HF were recruited for our monocentric observational study. Plasma ELABELA and Apelin levels were detected by immunoassay in all patients. Spearman correlation analysis was used to analyze the correlation between plasma ELABELA or Apelin levels and study variables. The receiver operating characteristic curves were used to access the predictive power of plasma ELABELA or Apelin levels. Plasma ELABELA levels were lower, while plasma Apelin levels were higher in HF patients than in non-HF patients. Plasma ELABELA levels were gradually decreased with increasing New York Heart Association grade or decreasing LVEF. Plasma ELABELA levels were negatively correlated with BNP, left atrial diameter, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, and left ventricular posterior wall thickness and positively correlated with LVEF in HF patients. In contrast, the correlation between plasma Apelin levels and these parameters is utterly opposite to ELABELA. The diagnostic value of ELABELA, Apelin, and LVEF for all HF patients was 0.835, 0.673, and 0.612; the sensitivity was 62.52, 66.20, and 32.97%; and the specificity was 95.92, 67.23, and 87.49%, respectively. All these parameters in HF patients with preserved ejection fraction were comparable to those in total HF patients. Overall, plasma ELABELA levels were significantly reduced and negatively correlated with cardiac function in HF patients. Decreased plasma ELABELA levels may function as a novel screening biomarker for HF. A combined assessment of BNP and ELABELA may be a good choice to increase the accuracy of the diagnosis of HF., (© 2024. The Author(s).)

Purpose: This study examines whether Angiopoietin Like 8 (ANGPTL8) is linked to cardiometabolic risk factors (CMRFs) in Saudi women with type 2 diabetes (T2DM)., Methods: Case-control investigation compared 150 women aged 30-60 with T2DM to 140 healthy women of the same age and gender., Results: ANGPTL8 levels differed significantly between T2DM and non-diabetics. Fasting blood glucose (FBG), insulin resistance (IR), triglycerides (TG), high-sensitivity C-reactive protein (hs-CRP), body mass index (BMI), and atherogenic index (AIP) of plasma all correlated positively with ANGPTL8 concentrations. Insulin levels correlated negatively with ANGPTL8. Multiple linear regression models showed that elevated ANGPTL8 independently predicted higher FBG, hs-CRP, IR, TG, and AIP in T2DM patients., Conclusion: The study found a significant association between ANGPTL8 levels and IR, hs-CRP, TG, AIP, and BMI in women with T2DM. These components are classified as CMRFs and have the potential to contribute to the development of cardiovascular disease (CVD)., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

We assessed the diagnostic potential of erythroferrone as a biomarker for iron homeostasis comparing iron deficiency cases with anaemia of inflammation and controls. The dysregulation of the hepcidin axis was observed by Latour et al. in a mouse model of malarial anaemia induced by prolonged Plasmodium infection leading to increased erythroferrone concentrations. In line with that, we found significantly higher erythroferrone levels in cases with malaria and anaemia in an African population, compared to asymptomatic controls. Therefore, our findings extend the previous ones of the mouse model, suggesting also a dysregulation of the hepcidin axis in humans, which should be further corroborated in prospective studies and may lay the basis for the development of improved treatment strategies according to ERFE concentrations in such patients., (© 2024 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Background: Iron overload can result in grave consequences in thalassemic patients, despite the availability of iron chelators. Therefore, alternative pathways aiming to reduce iron toxicity are currently investigated. Among which, reduction of iron absorption through control of hepcidin production appears to be promising. In this study, we investigated growth differentiation factor-15 (GDF15) and erythroferrone (ERFE) as potential suppressors of hepcidin., Methods: This cross-sectional study was conducted on 61 thalassemic patients and 60 healthy controls. The frequency of GDF15 gene polymorphism (rs4808793) (-3148C/G), serum level of GDF15 and erythroferrone were measured and correlated with those of hepcidin and serum ferritin., Results: The presence of GDF15 gene mutations were significantly higher in the patients' group compared to controls (P value 0.035). Also, thalassemia patients had significantly higher levels of GDF15 and ERFE and lower hepcidin levels than controls (P value < 0.001). Serum hepcidin level showed significantly negative correlations with GDF15, ERFE, reticulocyte count, LDH level, and serum ferritin. Contrarily, it had highly significant positive correlation with hemoglobin., Conclusions: High level of GDF15 and/or ERFE may inhibit hepcidin production and increase iron load in patients with thalassemia; therefore, medications that suppress their actions may provide new therapeutic potentials for iron toxicity., Impact: Iron overload continues to be a major contributor to high morbidity and mortality in patients with thalassemia. New strategies together with proper chelation, need to be developed to minimize the effect of iron toxicity. Growth differentiation factor-15 (GDF15) and erythroferrone (ERFE) inhibit hepcidin production and increase iron levels in conditions with ineffective erythropoiesis. Medications that suppress the production or interfere with the action of GDF15 or ERFE may represent new therapeutic potentials for iron toxicity. Prevention of iron toxicity will significantly reduce morbidity and mortality and improve the quality of life of thalassemia patients., (© 2023. The Author(s).)

Objectives: The aim of the study was to assess concentrations of the following neuropeptides: phoenixin, spexin and kisspeptin in venous blood serum of children and adolescents suffering from bipolar disorder, and by this their predictive efficiency in this disorder., Methods: The study covered 75 individuals with a mean age of 15.26 years (95% CI: 14.86-15.67), of which the study group comprised of 57 individuals diagnosed with bipolar affective disorder and the control group - 18 individuals with no psychiatric diagnosis and no pharmacological treatment. Phoenixin, spexin and kisspeptin levels were determined in the peripheral venous blood serum. Neuropeptide concentrations were measured with the enzyme-linked immunosorbent assay (ELISA)., Results: The mean phoenixin concentration in the studied group equalled 1.57 ng/ml (95% CI: 1.35-1.79), while in the control group - 2.69 ng/ml (95% CI: 2.38-3; U Mann-Whitney test p-value < 0.05). For spexin, these results were 639.65 pg/ml (95% CI: 558.86-720.44) in the studied group, and 354.28 pg/ml (95% CI: 310.33-398.22; U Mann-Whitney test p-value < 0.05) in the control group. The observed differences were statistically significant. The mean concentration of kisspeptin levels in the studied group was 126.02 pg/ml (95% CI: 39.82-212.23; median: 59.85), while in the control group - 54.83 pg/ml (95% CI: 39.23-70.43; median: 51.3; U Mann-Whitney test p-value = 0.29), and the observed difference was not statistically significant., Conclusions: The occurrence of bipolar disorder symptoms is statistically significantly linked with a decreased phoenixin concentration and to a small degree - with an increased spexin concentration in blood serum of patients. However, it is not linked with the kisspeptin concentration.

Background: Angiopoietin-like protein 3 (ANGPTL-3) modulates lipid metabolism and the risk of coronary artery disease (CAD), especially stable angina (SA), via suppressing lipoprotein lipase (LPL). However, whether there are other mechanisms is not elucidated yet. The current research explored the modulatory roles of ANGPTL-3 on high-density lipoprotein (HDL), which further affects atherosclerotic development., Methods: A total of 200 individuals were enrolled in the present study. Serum ANGPTL- 3 levels were detected via enzyme-linked immunosorbent assays (ELISA). Cholesterol efflux capacity induced by HDL particles was detected through H 3 -cholesterol loading THP-1 cell., Results: The serum ANGPTL-3 levels presented no significant discordance between the SA group and the non-SA group, whereas the serum ANGPTL-3 levels in type 2 diabetes mellitus (T2DM) group were significantly elevated compared with those in the non-T2DM group [428.3 (306.2 to 736.8) ng/ml vs. 298.2 (156.8 to 555.6) ng/ml, p <0.05]. Additionally, the serum ANGPTL-3 levels were elevated in patients with low TG levels compared to those in patients with high TG levels [519.9 (377.6 to 809.0) ng/ml vs. 438.7 (329.2 to 681.0) ng/ml, p <0.05]. By comparison, the individuals in the SA group and T2DM group presented decreased cholesterol efflux induced by HDL particles [SA: (12.21±2.11)% vs. (15.51±2.76)%, p <0.05; T2DM: (11.24±2.13)% vs. (14.65± 3.27)%, p <0.05]. In addition, the serum concentrations of ANGPTL-3 were inversely associated with the cholesterol efflux capacity of HDL particles (r=-0.184, p <0.05). Through regression analysis, the serum concentrations of ANGPTL-3 were found to be an independent modulator of the cholesterol efflux capacity of HDL particles (standardized β=-0.172, p <0.05)., Conclusion: ANGPTL-3 exhibited a negative modulatory function on cholesterol efflux capacity induced by HDL particles., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Erythroferrone (ERFE) has been identified as a hepcidin-regulating hormone synthetized by erythroblasts correlating to the erythropoietic activity and the needs for iron substrate in bone marrow of adults. The present study aimed to assess the ERFE serum concentrations and its predictors in infants., Methods: ERFE was explored at 4 time points during the first year of life in 45 healthy, breastfed, normal birth weight (NBW) infants, and 136 marginally low birth weight infants (LBW, 2000-2500 g) receiving iron (N = 58) or placebo (N = 78) between 6 weeks and 6 months of age., Results: ERFE concentrations were low at birth, increasing gradually during the first year of life. In NBW infants, reference ranges (5th to 95th percentile) were at 6 weeks <0.005-0.99 ng/mL and at 12 months <0.005-33.7 ng/mL. ERFE was higher in LBW infants at 6 weeks but lower at 12 months compared to NBW and minimally affected by iron supplementation among LBW infants. Correlations of ERFE with erythropoietic and iron status markers were weak and inconsistent., Conclusions: The role of ERFE in the crosstalk of erythropoiesis and iron homeostasis remains unclear in infants and further studies on ERFE in infants and older children are warranted within the framework of the erythropoietin-ERFE-hepcidin axis., Impact: Normal range of erythroferrone in healthy infants is described for the first time. Erythroferrone in infants lacks correlation to iron status and markers of erythropoiesis. The findings indicate differences in infant regulation of iron homeostasis as compared to adults. The findings point to a need to study infant erythropoiesis separately from its adult counterpart. The findings may have clinical impact on management strategies of iron-loading anemia in infancy., (© 2023. The Author(s).)

Background: Despite observable improvement in the treatment outcomes of patients with Prader-Willi syndrome (PWS), adequate weight control is still a clinical problem. Therefore, the aim of this study was to analyze the profiles of neuroendocrine peptides regulating appetite-mainly nesfatin-1 and spexin-in children with PWS undergoing growth hormone treatment and reduced energy intake., Methods: Twenty-five non-obese children (aged 2-12 years) with PWS and 30 healthy children of the same age following an unrestricted age-appropriate diet were examined. Serum concentrations of nesfatin-1, spexin, leptin, leptin receptor, total adiponectin, high molecular weight adiponectin, proinsulin, insulin-like growth factor-I, and total and functional IGF-binding protein-3 concentrations were determined using immunoenzymatic methods., Results: The daily energy intake in children with PWS was lower by about 30% ( p < 0.001) compared with the controls. Daily protein intake was similar in both groups, but carbohydrate and fat intakes were significantly lower in the patient group than the controls ( p < 0.001). Similar values for nesfatin-1 in the PWS subgroup with BMI Z-score < -0.5 and the control group, while higher values in the PWS subgroup with BMI Z-score ≥ -0.5 ( p < 0.001) were found. Spexin concentrations were significantly lower in both subgroups with PWS than the controls ( p < 0.001; p = 0.005). Significant differences in the lipid profile between the PWS subgroups and the controls were also observed. Nesfatin-1 and leptin were positively related with BMI ( p = 0.018; p = 0.001, respectively) and BMI Z-score ( p = 0.031; p = 0.027, respectively) in the whole group with PWS. Both neuropeptides also correlated positively in these patients ( p = 0.042)., Conclusions: Altered profiles of anorexigenic peptides-especially nesfatin-1 and spexin-in non-obese children with Prader-Willi syndrome during growth hormone treatment and reduced energy intake were found. These differences may play a role in the etiology of metabolic disorders in Prader-Willi syndrome despite the applied therapy.

Objective: In the present study, we aimed to investigate the role of the fasting serum levels of Anjiopoetın 2 - like protein (ANGPTL2), Anjiopoetın 8-like protein (ANGPTL8), and high-sensitivity C-reactive protein (hs-CRP) in the etiopathogenesis of gestational diabetes mellitus (GDM), and analyze the relationships between insulin resistance parameters., Material and Method: The 90 individuals admitted to İzmir Katip Celebi University Hospital Internal Medicine, Endocrinology and Obstetrics, and gynecology outpatient clinic were included in the study of similar ages and similar demographic characteristics. Forty-five women with diet-controlled GDM and 45 women with normoglycemic pregnancy were enrolled. ANGPTL-2, ANGPTL-8, hs-CRP, creatinine, ALT, GGT, lipid profile, HBA1c(%), and serum insülin, c-peptide levels were studied in the fasting serum samples of research groups. All individuals had 75-g OGTT testing. GDM screening was performed at 24-28 weeks' gestation. Exclusion criteria were as follows: Age <18 years or >40 years, pregestational diabetes (type 1 or 2), drug or alcohol abuse, thyroid dysfunction, Hepatitis B, and other infectious diseases (Herpes virus, Streptococcus B carriers, Chlamydia and Candida), Thalassemia carriers or other significant medical conditions, the use of any medication that interferes with lipid or glucose metabolism that would affect glucose regulation., Result: Forty-five women with GDM and for the control group, 45 women with normoglycemic pregnant women were identified. The mean gestational age was 30.7 (18-38) for GDM and 29.6 (24-39) for the control group. Serum ANGPTL-8 (GDM =19.5 ± 93 Control = 0.73 ± 3.78 p  = <.001). There was a statistically significant difference between the case and control groups for serum ANGPTL-8 levels. Serum ANGPTL-2 (GDM =19.9 ± 23.1 Control = 26.0 ± 23.4 p  = .105) and serum hs-CRP(GDM =106 ± 65.1 Control =98.2 ± 87.3 p  = .768). There was no statistically significant difference between the case and control groups for serum ANGPTL-2 and hsCRP levels. Serum ANGPTL8 levels were positively correlated with FPG ( r  = 0.391, p  = <.001), FPI ( r  = 0.212, p  = .045), 1-h PPG ( r  = 0.514, p = <.001), 2-h PPG ( r  = 0.502, p = <.001), HOMA-IR) score ( r  = 0.310, p  = .003), TG ( r  = 0.245, p  = .020); they were not except for BMI, hs-CRP levels and ANGPTL2 levels., Conclusions: ANGPTL8 levels were significantly higher in GDM than in healthy control group. ANGPTL2 levels and hs-CRP levels were similar to the healthy control group. Elevated serum ANGPTL8 levels were correlated significantly with insulin resistance parameters, the main component of GDM pathophysiology. Our data showed that ANGPTL8 could be a new biomarker for diagnosing GDM.

Objective: Children born small for gestational age (SGA) are at risk of future obesity and associated comorbidities. Therefore the identification of risk factors and novel biomarkers which are associated with this risk are needed for early detection and to improve preventive strategies. Spexin (SPX), a novel neuropeptide that is involved in the regulation of obesity and fat metabolism, is a candidate biomarker for predicting obesity and related comorbidities at an early age. The aim of this study was to investigate serum levels of SPX in term infants born small, appropriate, and large for gestational age (LGA) and its association with newborn anthropometric measurements., Methods: One hundred and twenty term newborn babies classified as SGA, appropriate for gestational age (AGA), or LGA and their mothers were included. SPX, leptin and visfatin were measured in cord blood and maternal serum by enzyme-linked immunosorbent assay., Results: Fifty-six (46.7%) neonates were girls and 64 (53.3%) were boys. The mean birth weight was 3170.70±663 g, birth length was 48.9±2.79 cm, and head circumference was 34.5±1.67 cm. Birth weights, lengths, and head circumferences of the neonates in the SGA, AGA, and LGA groups were significantly different. Cord blood SPX and leptin levels in the SGA groups were significantly lower than those of both the LGA and AGA groups. Cord blood visfatin levels were significantly lower in the AGA group than the LGA and SGA groups. Maternal SPX levels of SGA babies were significantly lower than those of the mothers in both the LGA and AGA groups, but no significant difference was observed between the SGA and LGA groups. Maternal visfatin levels of the AGA babies were significantly higher than the maternal levels of SGA and LGA groups. There was no difference in terms of maternal leptin levels. Cord blood SPX and leptin levels were positively correlated with birth weight, length and head circumference. Birth weight increased significantly in line with maternal pregestational body mass index., Conclusion: The lowest SPX levels were found in the SGA babies and cord SPX level was significantly correlated with newborn length, weight, and head circumference.

Polycystic ovarian syndrome (PCOS) is a common poignant endocrine disorder affecting women, posing a close association with metabolic syndrome and obesity. Existing literature characterizes PCOS with deranged levels of several adipokines and myokines. CTRP15 is a paralogue of adiponectin, mainly expressed by skeletal muscles, and plays a key role in insulin, glucose, and lipid metabolism. In the current study, we aim to determine the circulating levels of CTRP15 and evaluate its association with cardiometabolic and inflammatory parameters in PCOS women. This case-control study included 120 PCOS patients (60 Recurrent pregnancy loss (RPL) and 60 infertile (inf) PCOS) and 60 healthy non-PCOS controls. Serum levels of hs-CRP were measured by commercial kits, while serum levels of adiponectin and CTRP15 were determined using the ELISA technique. Serum levels of CTRP15 were significantly elevated in PCOS-RPL and PCOS-inf subgroups when compared to controls (94.80 ± 27.08 and 87.77 ± 25.48 vs. 54.78 ± 15.45, both P < 0.001). Moreover, serum adiponectin was considerably lower in the PCOS group and subgroups (P < 0.001), while serum hs-CRP, fasting insulin, HOMA-IR, and free testosterone were significantly higher when compared to the non-PCOS group (P < 0.05). Furthermore, CTRP15 closely associated with FSH, HOMA-IR, hs-CRP, and BMI. These results highlight a possible involvement of CTRP15 in the pathogenesis of PCOS. The elevated levels of CTRP15 might be a compensatory mechanism for the metabolic dysregulations (excess adiposity, insulin resistance, metaflammation) associated with the syndrome. Nevertheless, future studies are necessary to unravel the underlying mechanism., Competing Interests: The authors have declared that no competing interests ex.

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.

Objective: A retrospective cohort study aimed to explore the effects of different ovulation induction regimens on the levels of sex hormones and serum C1q/TNF-related protein-3 (CTRP3) and C1q/TNF-related protein-15 (CTRP15) in patients with PCOS., Methods: A total of 100 patients with PCOS treated in the department of gynecology and obstetrics from February 2019 to April 2021 in our hospital were enrolled. The patients were arbitrarily assigned into control group and study group. The treatment effect, pregnancy rate, ovulation rate, follicle size, thickness of endometrium, number of mature follicles and ovulation, serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), testosterone (T), serum CTRP3, CTRP15 and menstrual score were compared., Results: There exhibited no statistical difference in baseline clinical data between the two kinds of patients. The therapeutic effects were compared, the effective rate was 98.00% in the study group, 13 cases in the control group, 20 cases in the effective group and 7 cases in the control group, and the effective rate was 86.00%. The effective rate in the study group was higher (P <0.05). The size of follicles and the thickness of endometrium in the two groups were compared before and after intervention. There exhibited no significant difference in the size of follicles and the thickness of endometrium before and after intervention (P >0.05). The size of follicles and the thickness of endometrium in the study group were significantly higher (P <0.05). The size of follicles and the thickness of endometrium in the study group were significantly higher (P <0.05). There exhibited no significant difference in the number of mature follicles and ovulation before and after intervention (P >0.05). After intervention, the number of mature follicles and ovulation in the two groups increased. The number of mature follicles and ovulation in the study group were (4.76 ± 0.90) and (4.48 ± 0.73), respectively, which were higher compared to the control group (2.45 ± 0.86) and (2.82 ± 0.84), respectively (P <0.05). The levels of serum LH, FSH, E2 and T were not significantly different before and after intervention. After the intervention of different ways of ovulation induction, the levels of serum LH, FSH, E2 and T in the two groups continued to decrease, and the levels of the above sex hormones in the study group were significantly lower (P <0.05). The menstrual score and the levels of serum CTRP3 and CTRP15 were compared before and after intervention. After intervention, the menstrual score of patients in both groups decreased, and the menstrual score of the study group was lower. In addition, the levels of serum CTRP3 and CTRP15 in the two groups decreased after intervention. Compared with the control group, the levels of CTRP3 and CTRP15 in the study group were lower after intervention (P <0.05). The ovulation rate and pregnancy rate of the two groups were compared. In the study group, there were 45 ovulation cases, the ovulation rate was 90.00% (45/50), the pregnancy rate was 33 cases, the pregnancy rate was 66.00% (33/50), and the ovulation rate in the control group was 31 cases, the ovulation rate was 62.00% (31/50), the pregnancy rate was 20 cases, and the pregnancy rate was 40.00% (20/50). The ovulation rate and pregnancy rate in the study group were higher (P <0.05)., Conclusion: Different ovulation induction regimens have different effects on the levels of sex hormones and serum CTRP3 and CTRP15 in patients with PCOS. Long-acting follicular phase regimens can effectively promote the therapeutic effect of patients and increase the ovulation rate and pregnancy rate. In addition, it can also reduce the levels of serum LH, follicle stimulating FSH, E2 and testosterone T, and help to promote the levels of serum CTRP3 and CTRP15, which is worth popularizing and applying in clinic., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Maohua Ren et al.)

Background: CTRP15 is a prologue of adiponectin which has shown to have favourable effects on glucose and lipid metabolism. Studies have reported lower levels of CTRP15 in T2DM and metabolic syndrome; however, its circulating levels have not been evaluated in CAD patients., Methods: This case-control study was conducted on 190 angiographically confirmed coronary artery disease (CAD) patients and 70 controls. Serum levels of CTRP15, adiponectin, TNF-α, and IL-6 were measured using the ELISA technique., Results: CTRP15 was shown to occur in higher levels in CAD patients compared with controls. In CAD patients, CTRP15 showed a positive correlation with BMI, FBS, insulin, HOMA-IR, IL-6, and TNF-α and a negative correlation with HDL-C and adiponectin., Conclusion: Elevated levels of CTRP15 in CAD patients and the relation of CTRP15 with pathogenic conditions such as insulin resistance, inflammation, and decreased adiponectin and HDL-C suggest a possible compensatory response to these conditions in CAD patients.

Objectives: The link between excess adiposity and left ventricular hypertrophy is multifaceted with sparse data among youths. Given that adipokines/hepatokines may influence lipid metabolism in myocardium, we aimed to investigate the relation of the novel hepatokine angiopoietin-like protein 8 (ANGPTL8) and other adipokines with cardiac structure in a cohort of youths and explore to what extent these adipokines/hepatokines affect cardiac structure through lipids., Methods: A total of 551 participants (aged 15-28 years) from the Beijing Child and Adolescent Metabolic Syndrome Study (BCAMS) cohort underwent echocardiographic measurements plus a blood draw assayed for five adipokines/hepatokines including adiponectin, leptin, retinol binding protein 4, fibroblast growth protein 21 and ANGPTL8., Results: Both ANGPTL8 (β = -0.68 g/m 2.7 per z-score, P = 0.015) and leptin (β = -1.04 g/m 2.7 per z-score, P = 0.036) were significantly inversely associated with left ventricular mass index (LVMI) independent of classical risk factors. Total cholesterol and low-density lipoprotein cholesterol significantly mediated the ANGPTL8-LVMI association (proportion: 19.0% and 17.1%, respectively), while the mediation effect of triglyceride on the ANGPTL8-LVMI relationship was strongly moderated by leptin levels, significantly accounting for 20% of the total effect among participants with higher leptin levels. Other adipokines/hepatokines showed no significant association with LVMI after adjustment for body mass index., Conclusions: Our findings suggest ANGPTL8, particularly interacting with leptin, might have a protective role in cardiac remodeling among youths with risk for metabolic syndrome. Our results offer insights into the pathogenesis of the cardiomyopathy and the potential importance of tissue-tissue crosstalk in these effects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Feng, Wang, Dong, Wang, Zhong, Li, Fu, Xiao, Speakman, Li and Gao.)

The potential involvement of neuropeptide Q (NPQ) and chemerin (CHEM) in metabolic disorders is yet to be fully elucidated. The aim of this study was to evaluate serum concentrations of NPQ and CHEM and to establish their relationship with cardiometabolic risk factors among individuals with metabolic syndrome. A total of 66 patients with metabolic syndrome (MetS) and 83 healthy volunteers (non-MetS) underwent biochemical, blood pressure, and anthropometric measurements. The concentration of NPQ in the MetS group was significantly lower (0.47 (0.34 ; 0.54) vs. 0.52 (0.43 ; 0.60) ng/mL, p = 0.015) than in non-MetS, while there were no differences in CHEM level. In the entire study population, we observed several negative correlations between NPQ concentration and waist-hip ratio (WHR), visceral adipose tissue, diastolic blood pressure (DBP), triglycerides (TG) along with a positive correlation with high-density lipoprotein (HDL), total muscle mass, and CHEM. Moreover, a negative correlation was observed in the MetS group between NPQ and glycemia. CHEM showed no significant correlations with cardiometabolic risk factors in the study population. In a multiple regression model, the total muscle mass proved to be an independent factor determining NPQ concentration in the population ( p < 0.00000001, R 2 adj = 28.6%). NPQ seems to protect against metabolic disorders correlated with obesity. Thus, it is worth considering NPQ level as a candidate protective biomarker of metabolic syndrome complications.

Hypertriglyceridemia is an independent risk factor for coronary artery disease. Lipoprotein lipase (LPL) plays an essential role in the metabolism of triglyceride-rich lipoproteins (TRLs). Angiopoietin-like proteins ANGPTL3 and ANGPTL8 are shown to be important regulators of LPL activity. Increased concentrations of these proteins may reflect cardiovascular risk, and the treatment of patients with dyslipidemia with ANGPTLs inhibitors may decrease this risk. We assessed the gender-specific relationships of serum ANGPTL3 and ANGPTL8 with atherogenic lipid biomarkers and obesity in non-diabetic adults. The study comprised 238 participants aged 25-74 [122 with triglycerides (TG) <150 mg/dL (<1.7 mmol/L) and 116 with hypertriglyceridemia]. Total cholesterol, HDL-cholesterol, LDL-cholesterol, TG, C-reactive protein (CRP), glycated hemoglobin, apolipoprotein B, small dense LDL-C (sd-LDL-C), ANGPTL3, and ANGPTL8 were measured. Non-HDL-cholesterol, remnant cholesterol (remnant-C) concentrations, and body mass index (BMI) were calculated. Results: Women and men did not differ in terms of age, CRP levels, the percentage of obese subjects, and concentrations of atherogenic lipid biomarkers, except higher TG in males and higher ANGPTL3 concentrations in females. Positive correlations of both ANGPTLs with TG, remnant-C, and sdLDL-C levels were found in females. In males, only ANGPTL3 correlated positively with atherogenic biomarkers, but there were no correlations with ANGPTL8. Concentrations of ANGPTL3 were higher in obese men, whereas ANGPTL8 levels were higher in obese women. In women alone, ANGPTL8 showed very good discrimination power to identify subjects with hypertriglyceridemia (AUC = 0.83). Contrary to this, ANGPTL3 was a better discriminator of hypertriglyceridemia (AUC = 0.78) in male subjects. Regression models, adjusted for age, sex, and BMI showed a weak but significant effect of ANGPTL8 to increase the risk of hypertriglyceridemia. Conclusions: In females, ANGPTL8 is more strongly associated with TRLs metabolism, whereas in males, ANGPTL3 plays a more important role. We suggest sex differences be taken into consideration when applying new therapies with angiopoietin-like proteins inhibitors in the treatment of dyslipidemia.

Angiopoietin-like protein 8 (ANGPTL8) is an hepatokine altered in several metabolic conditions, such as obesity, type 2 diabetes, dyslipidemia and nonalcoholic fatty liver disease (NAFLD). We sought to explore whether ANGPTL8 is involved in NAFLD amelioration after bariatric surgery in experimental models and patients with severe obesity. Plasma ANGPTL8 was measured in 170 individuals before and 6 months after bariatric surgery. Hepatic ANGPTL8 expression was evaluated in liver biopsies of patients with severe obesity undergoing bariatric surgery with available liver pathology analysis ( n = 75), as well as in male Wistar rats with diet-induced obesity subjected to sham operation, sleeve gastrectomy or Roux-en-Y gastric bypass (RYGB) ( n = 65). The effect of ANGPTL8 on lipogenesis was assessed in human HepG2 hepatocytes under palmitate-induced lipotoxic conditions. Plasma concentrations and hepatic expression of ANGPTL8 were increased in patients with obesity-associated NAFLD in relation to the degree of hepatic steatosis. Sleeve gastrectomy and RYGB improved hepatosteatosis and reduced the hepatic ANGPTL8 expression in the preclinical model of NAFLD. Interestingly, ANGPTL8 inhibited steatosis and expression of lipogenic factors ( PPARG2 , SREBF1 , MOGAT2 and DGAT1 ) in palmitate-treated human hepatocytes. Together, ANGPTL8 is involved in the resolution of NAFLD after bariatric surgery partially by the inhibition of lipogenesis in steatotic hepatocytes.

Background: This study aimed to evaluate spexin as a novel blood marker and to describe the relationship of this peptide with selected biochemical metabolites measured during the transition period in dairy cows. Additionally, mRNA expression of the spexin gene as well as spexin receptors - galanin receptor type 2 and galanin receptor type 3, was investigated in several bovine tissues. Blood samples were collected at weekly intervals starting at 21 days before the estimated parturition day until 21 days in milk to determine concentrations of spexin, nonesterified fatty acids, β-hydroxybutyrate acid, total and active ghrelin, progesterone, glucose, insulin, IGF-I, triglycerides, cholesterol, leptin, corticosterone and 17-β-estradiol as well as the activity of aspartate transaminase, alkaline phosphatase and gamma-glutamyl transferase., Results: Spexin concentration decreased from 21 d before parturition to calving day and next it rose during the first 14 d of lactation. The lowest concentration of spexin was recorded on the calving day and it differed from the mean level of this peptide before parturition as well as postpartum. Moreover, differences were observed between mean spexin concentrations before and after calving. Spexin levels were moderately negatively correlated with NEFA (r = - 0.39) and total ghrelin contents (r = - 0.41), weakly correlated with BHBA (r = - 0.35) while they showed a moderate positive relationship with progesterone concentrations (r = 0.42). Moreover, we detected that mRNA expression of GALR2, GALR3 and SPX is present in various bovine tissues (kidney, bowel, rumen, spinal cord, lung, skeletal muscle, liver, heart, fat and spleen)., Conclusion: A negative correlation between spexin concentration and NEFA, BHBA and total ghrelin contents as well as a positive relationship with levels of progesterone, metabolites and hormones, which are key players in the dairy cow transition period, may confirm an important function of this peptide in metabolism regulation. Thus measurement of spexin concentration could provide useful supplementary information for dairy cow herd health monitoring., (© 2021. The Author(s).)

Objectives: It is hypothesized that novel neuropeptides such as phoenixin (PNX), spexin (SPX), and kisspeptin (KISS) are involved in the pathogenesis of eating disorders. The study presented here analyzed neuropeptide concentrations during the course of anorexia nervosa (AN) and aimed to correlate those values with anthropometric and psychometric measurements., Methods: A longitudinal study was carried outin 30 AN adolescent patients and 15 age-matched healthy female controls. Selected neuroprotein serum levels were analyzed in malnourished patients (accAN) and following partial weight recovery (norAN), and these values were compared with the control group., Results: In accAN patients, decreased serum PNX levels were detected while SPX serum concentrations were lower in the accAN and norAN patients. No differences were observed in KISS concentrations in all studied groups., Conclusions: In malnourished adolescent inpatients with AN, serum PNX and SPX level were decreased. The partial weight recovery normalized PNX concentrations but failed to normalize SPX levels. Therefore these two neuropeptides might be crucial for the etiology and course of the AN. The KISS levels did not change in the course of AN. The PNX levels were associated with some symptoms of eating disorders which may indicate its potential contribution in the regulation of emotions and behaviors in AN.

Background: Elabela/Toddler (ELA) is a novel endogenous ligand of the apelin receptor, whose signalling has emerged as a therapeutic target, for example, in cardiovascular disease and cancer. Shorter forms of ELA-32 have been predicted, including ELA-21 and ELA-11, but metabolism and stability of ELA-32 in humans is poorly understood. We, therefore, developed an LC-MS/MS assay to identify ELA-32 metabolites in human plasma and tissues., Method: Human kidney homogenates or plasma were incubated at 37 °C with ELA-32 and aliquots withdrawn over 2-4 h into guanidine hydrochloride. Proteins were precipitated and supernatant solid-phase extracted. Peptides were extracted from coronary artery, brain and kidney by immunoprecipitation or solid-phase extraction following acidification. All samples were reduced and alkylated before analysis on an Orbitrap mass spectrometer in high and nano flow mode., Results: The half-life of ELA-32 in plasma and kidney were 47.2 ± 5.7 min and 44.2 ± 3 s, respectively. Using PEAKS Studio and manual data analysis, the most important fragments of ELA-32 with potential biological activity identified were ELA-11, ELA-16, ELA-19 and ELA-20. The corresponding fragments resulting from the loss of C-terminal amino acids were also identified. Endogenous levels of these peptides could not be measured, as ELA peptides are prone to oxidation and poor chromatographic peaks., Conclusions: The relatively long ELA plasma half-life observed and identification of a potentially more stable fragment, ELA-16, may suggest that ELA could be a better tool compound and novel template for the development of new drugs acting at the apelin receptor., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: Irisin, Betatrophin and Zinc-α2-glycoprotein (ZAG) have been shown to be associated with insulin resistance (IR) and polycystic ovary syndrome (PCOS), respectively. The purpose of this study is to explore the potential accuracy of this combination of three cytokines in screening PCOS., Methods: 186 individuals were recruited for this study. Circulating Irisin, Betatrophin and ZAG concentrations were measured by enzyme-linked immunosorbent assay. The association between these serum biomarkers and PCOS was assessed by logistic regression analysis. Receiver operating curve (ROC) analysis was performed to evaluate the diagnostic value of these biomarkers for PCOS women., Results: In women with PCOS, serum Irisin and Betatrophin levels were markedly elevated compared to those in healthy controls (p<0.01), while ZAG levels were lower (p<0.01). PCOS women with IR (M-value<6.28) had lower circulating ZAG concentrations, and higher circulating Irisin and Betatrophin levels relative to PCOS women without IR (M-value ≥ 6.28). ROC curve analyses showed that the AUC for Irisin, ZAG and Betatrophin for predicting PCOS were 0.77, 0.83 and 0.85, respectively. In a joint ROC curves analysis of these serum markers and other parameters, the results showed that the AUC was 0.93, and the sensitivity and specificity were 82.1 % and 92.3 %, respectively., Conclusions: When compared to using single cytokine, the analysis of Irisin, ZAG and Betatrophin elevates the accuracy in diagnosing PCOS., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Hematopoietic cell transplantation (HCT) brings important alterations in erythropoiesis and iron metabolism. Hepcidin, which regulates iron metabolism, increases in iron overload or inflammation and decreases with iron deficiency or activated erythropoiesis. Erythroferrone (ERFE) is the erythroid regulator of hepcidin. We investigated erythropoiesis and iron metabolism after allogeneic HCT in 70 patients randomized between erythropoietin (EPO) treatment or no EPO, by serially measuring hepcidin, ERFE, CRP (inflammation), soluble transferrin receptor (sTfR, erythropoiesis), serum iron and transferrin saturation (Tsat; iron for erythropoiesis) and ferritin (iron stores). We identified biological and clinical factors associated with serum hepcidin and ERFE levels. Serum ERFE correlated overall with sTfR and reticulocytes and inversely with hepcidin. Erythroferrone paralleled sTfR levels, dropping during conditioning and recovering with engraftment. Inversely, hepcidin peaked after conditioning and decreased during engraftment. Erythroferrone and hepcidin were not significantly different with or without EPO. Multivariate analyses showed that the major determinant of ERFE was erythropoiesis (sTfR, reticulocytes or serum Epo). Pretransplant hepcidin was associated with previous RBC transfusions and ferritin. After transplantation, the major determinants of hepcidin were iron status (ferritin at all time points and Tsat at day 56) and erythropoiesis (sTfR or reticulocytes or ERFE), while the impact of inflammation was less clear and clinical parameters had no detectable influence. Hepcidin remained significantly higher in patients with high compared to low pretransplant ferritin. After allogeneic HCT with or without EPO therapy, significant alterations of hepcidin occur between pretransplant and day 180, in correlation with iron status and inversely with erythroid ERFE., (© 2021 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Objective: This study aimed to detect Elabela concentrations in the serum of normotensive pregnant women complicated with intrauterine growth restriction (IUGR) and compare them with the uncomplicated healthy pregnancies., Material and Methods: This prospective case-control study was performed from May 1, 2020 to September 30, 2020. Of the 92 pregnant patients included in the study, we enrolled 49 normotensive patients complicated with IUGR as the study group, and 43 normotensive healthy gestational age-matched and body mass index (BMI)-matched patients without IUGR or additional pregnancy complication as the control group. Demographic and clinical characteristics, and maternal serum Elabela concentrations were recorded., Results: Maternal serum Elabela levels were significantly lower in IUGR pregnancies (4.02±3.42 ng/mL) compared to healthy pregnant women (14.01±18.38 ng/mL, p<0.001). There was a positive intermediate correlation between maternal serum Elabela levels and the birth weight (r = 0.308, p = 0.004)., Conclusion: Maternal circulating levels of Elabela were significantly lower in IUGR pregnancies than in healthy pregnant women. Also, birth weight was positively correlated with maternal serum Elabela levels. We consider that Elabela might be a crucial biomarker of the pathophysiologic process in pregnancies complicated by IUGR., Competing Interests: Declaration of Competing Interest None, (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Background: Previous studies showed altered angiopoietin-like protein-8 (ANGPTL-8) and resistin circulating levels in type 2 diabetes mellitus (T2DM). Whether or not the alteration in ANGPTL-8 and resistin level can be a predictive maker for increased diabetic nephropathy risk remains unclear., Aim: To Investigate the possible association of ANGPTL-8 and resistin with DN, and whether this association is affected by NAFLD status., Methods: A total of 278 T2DM patients were enrolled. Serum levels of ANGPTL8, resistin, BMI, blood pressure, duration of diabetes, glycosylated hemoglobin (HbA1c), fasting blood glucose (FPG), hypersensitive C-reactive protein (hs-CRP), lipid profile, liver, and kidney function tests were assessed. The relationship between DN with ANGPTL8 and resistin was analyzed in the unadjusted and multiple-adjusted regression models., Results: Serum levels of ANGPTL8 and resistin were significantly higher in DN compared with T2DM subjects without DN (respectively; P <0.001), especially in non-NAFLD populations. ANGPTL8 and resistin showed positive correlation with hs-CRP (respectively; P <0.01), and negative correlation with estimated GFR (eGFR) (respectively; P =<0.001) but no significant correlation to HOMA-IR(respectively; P>0.05). Analysis showed ANGPTL8 levels were positively associated with resistin but only in T2DM patients with DN(r=0.1867; P <0.05), and this significant correlation disappeared in T2DM patients without DN. After adjusting for confounding factors, both ANGPTL8(OR=2.095, 95%CI 1.253-3.502 P=0.005) and resistin (OR=2.499, 95%CI 1.484-4.208 P=0.001) were risk factors for DN. Data in non-NAFLD population increased the relationship between ANGPTL8 (OR=2.713, 95% CI 1.494-4.926 P=0.001), resistin (OR=4.248, 95% CI 2.260-7.987 P<0.001)and DN. The area under the curve (AUC) on receiver operating characteristic (ROC) analysis of the combination of ANGPTL8 and resistin was 0.703, and the specificity was 70.4%. These data were also increased in non-NAFLD population, as the AUC (95%CI) was 0.756, and the specificity was 91.2%., Conclusion: This study highlights a close association between ANGPTL8, resistin and DN, especially in non-NAFLD populations. These results suggest that ANGPTL-8 and resistin may be risk predictors of DN., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Fan, Peng, Huang, Zou, Yu, Yang, Shi and Ma.)

Background: The role of ANGPTL3 and ANGPTL8 in lipid regulation in patients with very high levels of HDL-cholesterol and triglyceride is unknown., Objective: We examined plasma levels of ANGPTL3 and ANGPTL8 in subjects with hyperalphalipoproteinemia (HALP) and in those with severe hypertriglyceridemia (HTG)., Methods: Plasma ANGPTL3 and ANGPTL8 levels were measured by ELISA in 320 subjects, consisting of HALP subjects with HDL-cholesterol ≥100 mg/dl (n=90) and healthy controls (n=90) and subjects with triglyceride ≥886 mg/dl (n=89) and control subjects (n=51)., Results: The mean plasma ANGPTL3 level was significantly higher in the HALP group compared to that of the controls (297 ± 112 ng/mL vs. 230 ± 100 ng/mL, p<0.001). Similarly, the mean plasma ANGPTL8 level was also higher in the HALP group (30 ± 11 ng/mL vs. 20 ± 8 ng/mL, p<0.001). Both ANGPTL3 and ANGPTL8 levels positively correlated with HDL-cholesterol levels. In the severe HTG group, plasma ANGPTL3 level was significantly higher than those in the control group (223 ± 105 ng/mL vs. 151 ± 60 ng/mL, p<0.001), but not ANGPTL8 (23 ± 20 ng/mL vs. 31 ± 23 ng/mL in controls, p=0.028). Only ANGPTL3, but not ANGPTL8, levels positively correlated with triglyceride levels., Conclusion: Plasma level of ANGPTL3 was increased in both HALP and severe HTG whereas an increase in plasma level of ANGPTL8 was found only in HALP, and not in severe HTG, suggesting that both ANGPTL3 and ANGPTL8 might play distinct roles in lipid regulation on these two extremes of dyslipidemia., (Copyright © 2021. Published by Elsevier Inc.)

Background: Atrial fibrillation (AF) is a common arrhythmia in patients with hypertension. ELABELA, which has cardioprotective effects, is decreased in the plasma of patients with hypertension and might be associated with AF in the hypertensive population. This study aims to measure the ELABELA plasma levels in hypertension patients with and without AF and to analyse the related factors., Methods: A total of 162 hypertension patients with or without AF were recruited for our monocentric observational study. Subjects were excluded if they had a history of valvular heart disease, rheumatic heart disease, cardiomyopathy, thyroid diseases, or heart failure. The patients' histories were recorded, and laboratory examinations were conducted. Plasma ELABELA was detected by immunoassay. Echocardiographs were performed, and parameters were collected by two experienced doctors. Binary logistic regression analysis was used to identify the association between ELABELA plasma level and AF in patients with hypertension., Results: Plasma ELABELA levels were lower in hypertension patients with AF than in those without AF (2.0 [1.5, 2.8] vs. 4.0 [3.4, 5.0] ng/ml, P < 0.001). ELABELA levels were correlated with age, heart rate, BNP levels and left atrial dimension. In addition to the left atrial dimension, ELABELA plasma levels were associated with AF in patients with hypertension (OR 0.081, 95% CI 0.029-0.224, P < 0.001). ELABELA levels were further decreased in the persistent AF subgroup compared with the paroxysmal AF subgroup (1.8 [1.4, 2.5] vs. 2.2 [1.8, 3.0] ng/ml, P = 0.012) and correlated with HR, BNP and ESR levels., Conclusions: ELALABELA levels were decreased in hypertension patients with AF and further lowered in the persistent AF subgroup. Decreased ELABELA plasma levels were associated with AF in hypertension patients and may be an underlying risk factor., (© 2021. The Author(s).)

C-terminal α-amidation is the final and essential step in the biosynthesis of several peptide hormones. Peptidylglycine α-amidating monooxygenase (PAM) is the only known enzyme to catalyse this reaction. PAM amidating activity (AMA) is known to be present in human circulation, but its physiological role and significance as a clinical biomarker remains unclear. We developed a PAM-specific amidation assay that utilizes the naturally occurring substrate Adrenomedullin-Gly (ADM-Gly, 1-53). Using our amidation assay we quantified serum amidating activities in a large population-based cohort of more than 4900 individuals. A correlation of serum amidating activity with several clinical parameters including high blood pressure was observed. Increasing PAM-AMA was an independent predictor of hard outcomes related to hemodynamic stress such as cardiovascular mortality, atrial fibrillation and heart failure during long-term follow-up (8.8 ± 2.5 years). Moreover, results from an animal study in rats utilizing recombinant human PAM provide novel insights into the physiological role of circulating PAM and show its potential significance in circulating peptide amidation., (© 2021. The Author(s).)

Current markers of iron deficiency (ID), such as ferritin and hemoglobin, have shortcomings, and hepcidin and erythroferrone (ERFE) could be of clinical relevance in relation to early assessment of ID. Here, we evaluate whether exposure to altitude-induced hypoxia (2,320 m) alone, or in combination with recombinant human erythropoietin (rHuEPO) treatment, affects hepcidin and ERFE levels before alterations in routine ID biomarkers and stress erythropoiesis manifest. Two interventions were completed, each comprising a 4-wk baseline, a 4-wk intervention at either sea level or altitude, and a 4-wk follow-up. Participants ( n = 39) were randomly assigned to 20 IU·kg body wt -1 rHuEPO or placebo injections every second day for 3 wk during the two intervention periods. Venous blood was collected weekly. Altitude increased ERFE ( P ≤ 0.001) with no changes in hepcidin or routine iron biomarkers, making ERFE of clinical relevance as an early marker of moderate hypoxia. rHuEPO treatment at sea level induced a similar pattern of changes in ERFE ( P < 0.05) and hepcidin levels ( P < 0.05), demonstrating the impact of accelerated erythropoiesis and not of other hypoxia-induced mechanisms. Compared with altitude alone, concurrent rHuEPO treatment and altitude exposure induced additive changes in hepcidin ( P < 0.05) and ERFE ( P ≤ 0.001) parallel with increases in hematocrit ( P < 0.001), demonstrating a relevant range of both hepcidin and ERFE. A poor but significant correlation between hepcidin and ERFE was found ( R 2 = 0.13, P < 0.001). The findings demonstrate that hepcidin and ERFE are more rapid biomarkers of changes in iron demands than routine iron markers. Finally, ERFE and hepcidin may be sensitive markers in an antidoping context.

This study aimed to evaluate the concentration of plasma elabela (ELA) in patients with coronary heart disease (CHD) and its correlation with the disease classification.We enrolled 238 patients diagnosed by coronary angiography as CHD and 86 controls. The CHD group was divided into three subgroups: stable angina (SA), unstable angina (UAP), and acute myocardial infarction (AMI). The plasma levels of ELA were measured in all participants and compared among different groups. The relationship between ELA and CHD classification was analyzed.ELA levels were markedly higher by 10.71% in patients with CHD than in controls (P < 0.05). The concentration of ELA in UAP and AMI subgroups were higher than in controls and SA subgroup. The former difference was significant (P < 0.05), but the latter was not. In addition, the ELA concentration was not correlated with SYNTAX score, left ventricular ejection fraction, and other biochemical variables.The newfound hormone, ELA, significantly increased in patients with UAP and AMI. There is a tendency that ELA levels might be correlated with CHD classification, but not with lesion severity. ELA may play a role in acute coronary syndrome.

Erythroferrone (ERFE), the erythroid regulator of iron metabolism, inhibits hepcidin to increase iron availability for erythropoiesis. ERFE plays a pathological role during ineffective erythropoiesis as occurs in X-linked sideroblastic anemia (XLSA) and β-thalassemia. Its measurement might serve as an indicator of severity for these diseases. However, for reliable quantification of ERFE analytical characterization is indispensable to determine the assay's limitations and define proper methodology. We developed a sandwich ELISA for human serum ERFE using polyclonal antibodies and report its extensive analytical validation. This new assay showed, for the first time, the differentiation of XLSA and β-thalassemia major patients from healthy controls (p = 0.03) and from each other (p<0.01), showing the assay provides biological plausible results. Despite poor dilution linearity, parallelism and recovery in patient serum matrix, which indicated presence of a matrix effect and/or different immunoreactivity of the antibodies to the recombinant standard and the endogenous analyte, our assay correlated well with two other existing ERFE ELISAs (both R2 = 0.83). Nevertheless, employment of one optimal dilution of all serum samples is warranted to obtain reliable results. When adequately performed, the assay can be used to further unravel the human erythropoiesis-hepcidin-iron axis in various disorders and assess the added diagnostic value of ERFE., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Angiopoietin-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., Methods: This 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)., Results: At 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., Conclusion: ANGPTL8 levels are similar in PWS and controls and, overall, they are directly associated with the presence and severity of NAFLD in patients with PWS.

Introduction: To clarify mechanisms of ineffective erythropoiesis on iron metabolism, studies on erythroid factors that regulating hepcidin suppression have been carried out. The aim of the current study is to identify associations between erythropoiesis and iron homeostasis parameters in β-thalassemias., Materials and Methods: This study consisted of 83 subjects: 21 thalassemia major (TM), 20 thalassemia intermedia (TI), 20 thalassemia trait (TT), and 22 healthy subjects (HS). Erythroferrone (ERFE), hepcidin, growth differentiation factor-15 (GDF15), erythropoietin (EPO), and iron status parameters were measured., Results: Our results showed that TM and TI patients had higher hepcidin than the TT and control groups. The hepcidin/ferritin in TM patients was significantly lower than the other groups. GDF15 in TM and TI patients was significantly higher than in the TT and control groups. Also, TI group had significantly higher ERFE concentration and EPO activity when compared with the TM, TT, and HS groups. EPO activity showed positive correlation with ERFE and GDF15 concentrations. We could not find any correlation between ERFE and hepcidin concentrations., Conclusions: ERFE may be one of the parameters used to demonstrate erythropoietic activity level in thalassemias. More detailed studies are needed to clarify the role of ERFE in iron metabolism in the patients with thalassemias., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Bitter tastants are recently introduced as potential hunger-suppressive compounds, the so-called "Bitter pill." However, the literature about bitter administration lacks consistency in methods and findings. We want to test whether hunger ratings and hormone plasma levels are affected by: 1 ) the site of administration: intragastrically (IG) or intraduodenally (ID), 2 ) the bitter tastant itself, quinine hydrochloride (QHCl) or denatonium benzoate (DB), and 3 ) the timing of infusion. Therefore, 14 healthy, female volunteers participated in a randomized, placebo-controlled six-visit crossover study. After an overnight fast, DB (1 µmol/kg), QHCl (10 µmol/kg), or placebo were given IG or ID via a nasogastric feeding tube. Blood samples were taken 10 min before administration and every 10 min after administration for a period of 2 h. Hunger was rated at the same time points on a visual analogue scale. ID bitter administration did not affect hunger sensations, motilin, or acyl-ghrelin release compared with its placebo infusion. IG QHCl infusion tended to suppress hunger increase, especially between 50 and 70 min after infusion, simultaneously with reduced motilin values. Here, acyl-ghrelin was not affected. IG DB did not affect hunger or motilin, however acyl-ghrelin levels were reduced 50-70 minutes after infusion. Plasma values of glucagon-like peptide 1 and cholecystokinin were too low to be properly detected or to have any physiological relevance. In conclusion, bitter tastants should be infused into the stomach to reduce hunger sensations and orexigenic gut peptides. QHCl has the best potential to reduce hunger sensations, and it should be infused 60 min before food intake. NEW & NOTEWORTHY Bitter tastants are a potential new weight-loss treatment. This is a noninvasive, easy approach, which should be received with considerable enthusiasm by the public. However, literature about bitter administration lacks consistency in methods and findings. We summarize how the compound should be given based on: the site of administration, the best bitter compound to use, and at what timing in respect to the meal. This paper is therefore a fundamental step to continue research toward the further development of the "bitter pill."

Background: ANGPTL8, an important regulator of lipid metabolism, was recently proven to have additional intracellular and receptor-mediated functions. This study aimed to investigate circulating levels of ANGPTL8 and its potential association with the risk of kidney function decline in a cohort study., Methods: We analysed 2,311 participants aged 40 years old and older from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. Kidney function decline was defined as an estimated glomerular filtration rate (eGFR) less than 60 mL per minute per 1.73 m 2 of body surface area, a decrease in eGFR of ≥ 30% from baseline, chronic kidney disease (CKD)-related hospitalization or death, or end-stage renal disease. The association between baseline ANGPTL8 levels and kidney function decline was assessed using multivariable-adjusted Cox proportional hazards models, and inverse possibility of treatment weight (IPTW) was utilized to prevent overfitting., Results: There were 136 (5.9%) cases of kidney function decline over a median of 3.8 years of follow-up. We found that serum ANGPTL8 levels at baseline were elevated in individuals with kidney function decline compared to those without kidney function decline during follow-up (718.42 ± 378.17 vs. 522.04 ± 283.07 pg/mL, p < 0.001). Compared with the first quartile, multivariable-adjusted hazard ratio (95% confidence intervals [CIs]) for kidney function decline was 2.59 (95% CI, 1.41-4.77) for the fourth ANGPTL8 quartile. Furthermore, compared with patients in the first ANGPTL8 quartile, those in the fourth ANGPTL8 quartile were more likely to report a higher stage of CKD (relative risk: 1.33; 95% CI, 1.01-1.74). The conclusions of the regression analyses were not altered in the IPTW models. Multivariable-adjusted restricted cubic spline analyses suggested a linear relationship of ANGPTL8 with kidney function decline (p for nonlinear trend = 0.66, p for linear trend < 0.001)., Conclusions: Participants with higher circulating ANGPTL8 levels were at increased risk for kidney function decline, highlighting the importance of future studies addressing the pathophysiological role of ANGPTL8 in CKD.

This study was conducted as part of a larger study of East Tyrolean health tourism, and investigates the effects of an active seven-day vacation on metabolic parameters and adipokines. Fifty-two healthy vacationers participated in two types of vacation activities (golf vs. Nordic walking or e-biking [nw&eb]). In the former group, 30 subjects played golf for a mean duration of 33.5 h per week; in the NW&EB group, 22 persons performed Nordic walking or e-biking for a mean duration of 14.2 h per week. Metabolic parameters and adipokines, such as leptin, adiponectin, GF-21, irisin, omentin-1, betatrophin, and resistin, were measured one day before and one day after the stay. After one week, only the NW&EB group experienced a significant decrease of 1.0 kg in body weight. Significant changes in HDL-C, FGF-21, irisin, and omentin-1 were seen in the golf group; and in triglycerides, HbA1c, leptin and adiponectin in the NW&EB group. No significant changes in betatrophin or resistin were registered in either group. A seven-day vacation with an activity program for several hours per week causes favorable changes in metabolic parameters and adipokines known to be involved in the pathophysiology of the metabolic syndrome. The changes differed in their magnitude and significance, depending on the type of activity., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Angiopoietin-like proteins (ANGPTLs) are closely related to insulin resistance and lipid metabolism, and may be a key in metabolic syndrome. Non-alcoholic fatty liver disease (NAFLD) (newly named metabolic-associated fatty liver disease (MAFLD)) is based on metabolic dysfunction. There may be some correlation between ANGPTLs and MAFLD, but the specific correlation is unclear. This study aims to explore the predictive role of ANGPTLs in MAFLD and its progression., Methods: Seven databases (PubMed, EMBASE, Cochrane Library, CNKI, WANFANG, CBM and Clinicaltrials.gov ) were searched with free terms and MeSH terms. The random-effects model was used to pool the data, and Standardized Mean Difference (SMD) and 95% confidence intervals (CI) were taken as the overall outcome. No language restrictions existed in the article selection. RevMan 5.3, Stata 16 and MetaXL software were applied to analyse the data and the GRADE system was utilized to assess the certainty of evidence., Results: After reviewing 823 related articles, 13 studies (854 cases and 610 controls) met the inclusion criteria, and contributed to this meta-analysis. The results showed that circulating ANGPTL8 level was significantly elevated in the MAFLD group than in the healthy control group (SMD = 0.97 pg/mL, 95%CI: 0.77, 1.18). Conversely, there was no significant difference in the ANGPTL4 (SMD = 0.11 ng/mL, 95%CI: - 0.32, 0.54) and ANGPTL3 (SMD = - 0.95 ng/mL, 95%CI: - 4.38, 2.48) between the two groups. Subgroup analysis showed that: 1) the MAFLD group had significantly higher ANGPTL8 levels than the healthy control group in Asian and other races; 2) the ANGPTL8 levels in Body Mass Index (BMI) > 25 kg/m 2 patients with MAFLD were higher than those in the healthy control group; 3) the higher ANGPTL8 levels were observed in moderate to severe MAFLD group than the healthy control group. Meta-regression demonstrated that BMI might effectively explain the high heterogeneity. No significant publication bias existed (P > 0.05). The certainty of evidence was assessed as very low by the GRADE system., Conclusions: The ANGPTLs may be related to MAFLD. The increased ANGPTL8 level may be positively correlated with different situations of MAFLD, which may act as a potential indicator to monitor the development trends.

Context: ANGPTL8 (A8) plays a key role in determining the tissue fate of circulating triglycerides (TGs). Plasma A8 levels are associated with several parameters of glucose and TG metabolism, but the causality of these relationships and the contribution of genetic variants to differences in A8 levels have not been explored., Objective: To characterize the frequency distribution of plasma A8 levels in a diverse population using a newly-developed enzyme-linked immunosorbent assay (ELISA) and to identify genetic factors contributing to differences in plasma A8 levels., Methods: We studied a population-based sample of Dallas County, comprising individuals in the Dallas Heart Study (DHS-1, n = 3538; DHS-2, n = 3283), including 2131 individuals with repeated measurements 7 to 9 years apart (age 18-85 years; >55% female; 52% Black; 29% White; 17% Hispanic; and 2% other). The main outcome measures were associations of A8 levels with body mass index (BMI), plasma levels of glucose, insulin, lipids, and hepatic TGs, as well as DNA variants identified by exome-wide sequencing., Results: A8 levels varied over a 150-fold range (2.1-318 ng/mL; median, 13.3 ng/mL) and differed between racial/ethnic groups (Blacks > Hispanics > Whites). A8 levels correlated with BMI, fasting glucose, insulin, and TG levels. A variant in A8, R59W, accounted for 17% of the interindividual variation in A8 levels but was not associated with the metabolic parameters correlated with plasma A8 concentrations., Conclusions: A8 levels were strongly associated with indices of glucose and TG metabolism, but the lack of association of genetic variants at the A8 locus that impact A8 levels with these parameters indicates that differences in A8 levels are not causally related to the associated metabolic phenotypes., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)

Spexin (SPX), a neuropeptide with diverse functions, is a novel satiety factor in fish models and its role in feeding control has been recently confirmed in mammals. In mouse, food intake was shown to trigger SPX expression in glandular stomach with parallel rise in serum SPX and these SPX signals could inhibit feeding via central actions within the hypothalamus. However, the mechanisms for SPX regulation by food intake are still unclear. To examine the role of insulin signal caused by glucose uptake in SPX regulation, the mice were IP injected with glucose and insulin, respectively. In this case, serum SPX was elevated by glucose but not altered by insulin. Meanwhile, SPX transcript expression in the glandular stomach was up-regulated by glucose but the opposite was true for insulin treatment. Using in situ hybridization, the differential effects on SPX gene expression were located in the gastric mucosa of glandular stomach. Co-injection experiments also revealed that glucose stimulation on serum SPX and SPX mRNA expressed in glandular stomach could be blocked by insulin. In gastric mucosal cells prepared from glandular stomach, the opposite effects on SPX transcript expression by glucose and insulin could still be noted with similar blockade of the stimulatory effects of glucose by insulin. In this cell model, SPX gene expression induced by glucose was mediated by glucose uptake via GLUT, ATP synthesis by glycolysis/respiratory chain, and subsequent modulation of K ATP channel activity, but the voltage-sensitive Ca 2+ channels were not involved. The corresponding inhibition by insulin, however, was mediated by PI3K/Akt, MEK 1/2 /ERK 1/2 , and P 38 MAPK cascades coupled to insulin receptor but not IGF-1 receptor. Apparently, glucose uptake in mice can induce SPX expression in the glandular stomach through ATP synthesis via glucose metabolism and subsequent modification of K ATP channel activity, which may contribute to SPX release into circulation to act as the satiety signal after food intake. The insulin rise caused by glucose uptake, presumably originated from the pancreas, may serve as a negative feedback to inhibit the SPX response by activating MAPK and PI3K/Akt pathways in the stomach., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chen, He, Lei, Ko, Lin, Bian and Wong.)

In a two-part process, we assessed elements of the principal hormonal pathway regulating iron homeostasis in human neonates. Part 1: Quantifying erythropoietin (Epo), erythroferrone (ERFE), hepcidin, and relevant serum and erythrocytic iron-related metrics in umbilical cord blood from term (n = 13) and preterm (n = 10) neonates, and from neonates born to mothers with diabetes and obesity (n = 13); Part 2: Quantifying serum Epo, ERFE, and hepcidin before and following darbepoetin administration. Part 1: We measured Epo, ERFE and hepcidin in all cord blood samples. Epo and ERFE levels did not differ between the three groups. Preterm neonates had the lowest hepcidin levels, while neonates born to diabetic women with a very high BMI had the lowest ferritin and RET-He levels. Part 2: Following darbepoetin dosing, ERFE levels generally increased (p < 0.05) and hepcidin levels generally fell (p < 0.05). Our observations suggest that the Epo/ERFE/hepcidin axis is intact in the newborn period., (Copyright © 2021. Published by Elsevier Inc.)

Abstract: To determine the association of betatrophin amounts with 25-(OH)D levels in gestational diabetes mellitus (GDM) patients, and to provide new targets for the prevention and treatment of GDM.This study included 40 GDM patients (GDM group) and 37 healthy pregnant women (control group). Betatrophin, 25-(OH)D, fasting blood glucose (FBG), HbA1c, hsCRP, and FINS levels in peripheral blood, as well as betatrophin and 25-(OH)D amounts in cord blood, were measured. Then, associations of betatrophin levels with 25-(OH)D amounts and other indexes were determined.Maternal (P = .011) and cord (P = .022) blood betatrophin levels were significantly lower in the GDM group compared with control group. Cord blood betatrophin levels were higher compared with maternal blood amounts in both the GDM and control groups (both P = .000). Serum betatrophin levels were positively associated with 25-(OH)D levels (r = 0.677, P = .000), but negatively associated with hsCRP (r = -0.335, P = .037) and HOMA-IR (r = -0.346, P = .031) levels in the GDM group. Fetal weight was higher in the GDM group compared with control group (P = .023), and negatively associated with cord blood betatrophin amounts in the GDM group (r = -0.342, P = .031). However, cord blood betatrophin levels were not significantly associated with body length, Apgar score, and cord blood 25-(OH)D levels in the GDM group (all P > .05).Serum betatrophin and 25-(OH) D levels were positively associated in women with GDM, and both significantly lower compared with control values. Fetal weight was higher in the GDM group and associated with cord blood betatrophin. These findings provide insights into developing new predictive biomarkers or therapeutic targets for GDM., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: This study aimed to investigate the expression characteristics of ANGPTL8 in patients with primary nephrotic syndrome and its possible correlation with hyperlipidemia and proteinuria., Methods: ANGPTL8 levels were determined using an enzyme-linked immunosorbent assay in 133 subjects with PNS and 60 healthy controls., Results: Compared with healthy controls, subjects with primary nephrotic syndrome had higher levels of serum and urine ANGPTL8 (P < 0.001). In primary nephrotic syndrome patients, serum ANGPTL8 was positively correlated with cholesterol (r = 0.209, P < 0.05) and triglycerides (r = 0.412, P < 0.001), while there was no correlation with 24 hUTP. Urine ANGPTL8 was positively correlated with high-density lipoprotein cholesterol (r = 0.181, P < 0.05) and was significantly negatively correlated with creatinine (r = - 0.323, P < 0.001), eGFR (r = - 0, P < 0.001) and 24 hUTP (r = - 0.268, P = 0.002). Interestingly, the urine ANGPTL8 concentrations in membranous nephropathy and mesangial proliferative glomerulonephritis pathological types were different., Conclusions: Serum and urine ANGPTL8 levels in primary nephrotic syndrome patients were correlated with blood lipid levels and proteinuria, respectively, suggesting that ANGPTL8 may play a role in the development of primary nephrotic syndrome hyperlipidemia and proteinuria.