Ameliorating effects of adropin on letrozole-induced polycystic ovary syndrome via regulating steroidogenesis and the microbiota inflammatory axis in rats.

Growing evidence supports the role of gut microbiota in chronic inflammation, insulin resistance (IR) and sex hormone production in polycystic ovary syndrome (PCOS). Adropin plays a pivotal role in the regulation of glucose and lipid metabolism and is negatively correlated with IR, which affects intestinal microbiota and sex hormones. However, the effect of adropin administration in PCOS has yet to be investigated. The present study aimed to assess the effects of adropin on letrozole (LTZ)-induced PCOS in rats and the potential underlying mechanisms. The experimental groups were normal, adropin, letrozole and LTZ + adropin. At the end of the experiment, adropin significantly ameliorated PCOS, as evidenced by restoring the normal ovarian structure, decreasing the theca cell thickness in antral follicles, as well as serum testosterone and luteinizing hormone levels and luteinizing hormone/follicle-stimulating hormone ratios, at the same time as increasing granulosa cell thickness in antral follicles, oestradiol and follicle-stimulating hormone levels. The ameliorating effect could be attributed to its effect on sex hormone-binding globulin, key steroidogenic genes STAR and CYP11A1, IR, lipid profile, gut microbiota metabolites-brain-ovary axis components (short chain fatty acids, free fatty acid receptor 3 and peptide YY), intestinal permeability marker (zonulin and tight junction protein claudin-1), lipopolysaccharides/Toll-like receptor 4/nuclear factor kappa B inflammatory pathway and oxidative stress makers (malondialdehyde and total antioxidant capacity). In conclusion, adropin has a promising therapeutic effect on PCOS by regulating steroidogenesis, IR, lipid profile, the gut microbiota inflammatory axis and redox homeostasis. KEY POINTS: Adropin treatment reversed endocrine and ovarian morphology disorders in polycystic ovary syndrome (PCOS). Adropin regulated the ovarian steroidogenesis and sex hormone-binding globulin in PCOS. Adropin improved lipid profile and decreased insulin resistance in PCOS. Adropin modulated the components of the gut-brain-ovary axis (short chain fatty acids, free fatty acid receptor 3 and peptide YY) in PCOS. Adropin improved intestinal barrier integrity, suppressed of lipopolysaccharides/Toll-like receptor 4/nuclear factor kappa B signalling pathway and oxidative stress in PCOS.

Adropin, a novel hepatokine: localization and expression during postnatal development and its impact on testicular functions of pre-pubertal mice.

Adropin, a multifaceted peptide, was identified as a new metabolic hormone responsible for regulating gluco-lipid homeostasis. However, its role in the testicular function is not yet understood. We aimed to investigate the localization and expression of adropin and GPR19 during different phases of postnatal development. Immunohistochemical study revealed the intense reactivity of adropin in the Leydig cells during all phases of postnatal development, while GPR19 showed intense immunoreactivity in the pachytene spermatocytes and mild immunoreactivity in Leydig cells as well as primary and secondary spermatocytes. Western blot study revealed maximum expression of GPR19 in pre-pubertal mouse testis that clearly indicates maximum responsiveness of adropin during that period. So, we hypothesized that adropin may act as an autocrine/paracrine factor that regulates pubertal changes in mouse testis. To examine the effect of adropin on pubertal onset, we gave bilateral intra-testicular doses (0.5 and 1.5 µg/testis) to pre-pubertal mice. Adropin treatment promoted testicular testosterone synthesis by increasing the expression of StAR, 3ß-HSD, and 17ß-HSD. Adropin also promoted germ cell survival and proliferation by upregulating the expression of PCNA and downregulating the Bax/Bcl2 ratio and Caspase 3 expression resulting in fewer TUNEL-positive cells in adropin-treated groups. FACS analysis demonstrated that adropin treatment not only increases 1C to 4C ratio but also significantly increases the 1C (spermatid) and 1C to 2C ratio which demarcates accelerated germ cell differentiation and turnover of testicular cells. In conclusion, adropin promotes steroidogenesis, germ cell survival, as well as the proliferation in the pre-pubertal mouse testis that may hasten the pubertal transition in an autocrine/paracrine manner.

Protective roles of adropin in neurological disease.

Adropin is a highly conserved secreted peptide encoded by the Energy Homeostasis Associated gene (Enho). It is expressed in many tissues throughout the body, including the liver and brain, and plays a crucial role in maintaining lipid homeostasis and regulating insulin sensitivity. Adropin also participates in several other pathophysiological processes of multiple central nervous system (CNS) diseases. There is strong evidence of the protective effects of adropin in stroke, heart disease, aging, and other diseases. The peptide has been shown to reduce the risk of disease, attenuate histological alterations, and reduce cognitive decline associated with neurological disorders. Recent findings support its critical role in regulating endothelial cells and maintaining blood-brain barrier integrity through an endothelial nitric oxide synthase (eNOS)-dependent mechanism. Here we discuss current evidence of the protective effects of adropin in CNS diseases specifically involving the cerebrovasculature and highlight potential mechanisms through which the peptide exhibits these effects.

Low-dose adropin stimulates inflammasome activation of macrophage via mitochondrial ROS involved in colorectal cancer progression.

Adropin is encoded by the energy homeostasis-associated (ENHO) gene and widely present in liver, pancreas, heart, kidney, brain, and vascular tissues. Abnormal adropin is associated with metabolic, inflammatory, immune, and central nervous disorders. Whether adropin is involved in the development of colorectal cancer (CRC) is still unclear. Here, decreased adropin expression of tumor-nest cells in advanced-stage CRC was demonstrated. Adropin expressed by carcinoma cells was negatively correlated with macrophage infiltration in the matrix of CRC tissues. However, tumor macrophages enhanced adropin expression and were positively correlated with tumor invasion and metastasis. ENHO gene transfection into colon cancer (MC38) cells inhibited tumor growth in vivo, accompanying the increase of M1 macrophages. Treatment with low-dose adropin (< 100 ng/mL) on macrophages ex vivo directly increased mitochondrial reactive oxygen species for inflammasome activation. Furthermore, ENHO-/- mice had less M1 macrophages in vivo, and ENHO-/- macrophages were inert to be induced into the M1 subset ex vivo. Finally, low-dose adropin promoted glucose utilization, and high-dose adropin enhanced the expression of CPT1α in macrophages. Therefore, variations of adropin level in carcinoma cells or macrophages in tumor tissues are differently involved in CRC progression. Low-dose adropin stimulates the antitumor activity of macrophages, but high-dose adropin facilitates the pro-tumor activity of macrophages. Increasing or decreasing the adropin level can inhibit tumor progression at different CRC stages.

Serum Levels of Adropin Improve the Predictability of MELD and Child-Pugh Score in Cirrhosis: Results of Proof-of-Concept Clinical Trial.

Adropin is a peptide that was suggested to have a role in cirrhosis. The present study aimed to determine the ability to use serum adropin levels to improve their prediction accuracy as an adjunct to the current scores. In a single-center, proof-of-concept study, serum adropin levels were determined in thirty-three cirrhotic patients. The data were analyzed in correlation with Child-Pugh and MELD-Na scores, laboratory parameters, and mortality. Adropin levels were higher among cirrhotic patients that died within 180 days (1,325.7 ng/dL vs. 870.3 ng/dL, p = 0.024) and inversely correlated to the time until death (r 2 = 0.74). The correlation of adropin serum levels with mortality was better than MELD or Child-Pough scores (r 2 = 0.32 and 0.38, respectively). Higher adropin levels correlated with creatinine (r 2 = 0.79. p < 0.01). Patients with diabetes mellitus and cardiovascular diseases had elevated adropin levels. Integrating adropin levels with the Child-Pugh and MELD scores improved their correlation with the time of death (correlation coefficient: 0.91 vs. 0.38 and 0.67 vs. 0.32). The data of this feasibility study suggest that combining serum adropin with the Child-Pugh score and MELD-Na score improves the prediction of mortality in cirrhosis and can serve as a measure for assessing kidney dysfunction in these patients.

Adropin and MOTS-c as new peptides: Do levels change in neurodegenerative diseases and ischemic stroke?

BACKGROUND: Neurological diseases such as Alzheimer's disease and Parkinson's disease (AD, PD), acute ischemic stroke (AIS), and multiple sclerosis (MS) are thought to be deeply affected by changes in the pathophysiological processes of neurons. As new peptides, it was aimed to evaluate the level of adropin and MOTS-c (mitochondrial open reading frame of the 12S rRNA-c) and its possible relationship with NSE (neuron-specific enolase) and NF-L (neurofilament light chain) in terms of neuronal interaction. METHODS: This study was conducted with 32 patients from each subgroup and group-appropriate controls. Disease identifiers and hemogram/biochemical parameters specific to the groups of participants were obtained. Additionally, plasma adropin, MOTS-c, NSE, and NF-L levels were evaluated by the ELISA method. RESULTS: Plasma adropin levels were decreased in the AD group and decreased in MOTS-c, AIS, and AD groups compared to the control (p < 0.05). Similar values were found in the MS group compared to its control (p > 0.05). In correlation analysis of these markers with laboratory parameters, while platelet and cholesterol levels were negatively correlated with adropin levels; platelet, lymphocyte, and triglyceride levels were positively correlated with MOTS-c (p < 0.05). CONCLUSION: This study provides new information about adropin may be potentially important markers in AD and MOTS-C in AIS and AD. Future studies are needed to examine the relationship between changes in metabolic profiles and these peptides.

Circulating levels of adropin and diabetes: a systematic review and meta-analysis of observational studies.

OBJECTIVE: Adropin, a newly identified regulatory protein has garnered attention given its potential role in metabolism regulation, especially glucose metabolism and insulin resistance. However, studies on the association between adropin and type 2 diabetes mellitus (T2DM) are equivocal. The aim of this study is to assess the association between serum adropin levels and T2DM using a systematic review and meta-analysis of observational studies. METHODS: PubMed, Scopus, ISI Web of science, and Google Scholar were searched, up to August 2022, for studies that reported the association between serum levels of adropin in adults with T2DM compared to a control group without diabetes. A random-effect model was used to compute the pooled weighted mean difference (WMD) with 95% confidence intervals (CI). RESULTS: Meta-analysis of 15 studies (n = 2813 participants) revealed that the serum adropin concentrations were significantly lower in patients with T2DM compared with the control group (WMD= -0.60 ng/mL, 95% CI: -0.70 to -0.49; I2 = 99.5%). Subgroup analysis also found lower concentration of adropin in patients with T2DM who were otherwise healthy compared to a control group (n = 9; WMD=-0.04 ng/ml, 95% CI= -0.06 to -0.01, p = 0.002; I2 = 96.4). CONCLUSIONS: Our study showed adropin levels are lower in patients with diabetes compared to a control group without diabetes. However, the limitations of observational studies challenge the validity of the results, and further investigations are needed to confirm the veracity of these findings and additionally explore possible mechanisms.

Effects of adropin on learning and memory in rats tested in the Morris water maze.

Adropin is a secreted peptide, which is composed of 43 amino acids and shows an effective role in regulating energy metabolism and insulin resistance. Motor coordination and locomotor activity were improved by adropin in the cerebellum. However, it is not known whether adropin administration has an effect on spatial learning and memory. In this study, we investigated the effect of adropin on spatial learning and memory and characterized the biochemical properties of adropin in the hippocampus. Thirty male Sprague-Dawley rats were randomly divided into two groups as control and adropin groups. The control group received 0.9% NaCl intracerebroventricular for 6 days, while the adropin groups received 1 nmol of adropin dissolved in 0.9% NaCl (for 6 days). The Morris water maze, Y maze, and object location recognition tests were performed to evaluate learning and memory. Also, the locomotor activity tests were measured to assess the motor function. The expression of Akt, phospho-Akt, CREB, phospho-CREB, Erk1/2, phospho-Erk1/2, glycogen synthase kinase 3 ß (GSK3ß), phospho-GSK3ß, brain-derived neurotrophic factor (BDNF), and N-methyl-d-aspartate receptor NR2B subunit were determined in the hippocampal tissues by using western blot. Behavior tests showed that adropin significantly increase spatial memory performance. Meanwhile, the western blot analyses revealed that the phosphorylated form of the Akt and CREB were enhanced with adropin administration in the hippocampus. Also, the expression of BDNF showed an enhancement in adropin group in comparison to the control group. In conclusion, we have shown for the first time that adropin exerts its enhancing effect on spatial memory capacity through Akt/CREB/BDNF signaling pathways.

Role of adropin in arterial stiffening associated with obesity and type 2 diabetes.

Adropin is a peptide largely secreted by the liver and known to regulate energy homeostasis; however, it also exerts cardiovascular effects. Herein, we tested the hypothesis that low circulating levels of adropin in obesity and type 2 diabetes (T2D) contribute to arterial stiffening. In support of this hypothesis, we report that obesity and T2D are associated with reduced levels of adropin (in liver and plasma) and increased arterial stiffness in mice and humans. Establishing causation, we show that mesenteric arteries from adropin knockout mice are also stiffer, relative to arteries from wild-type counterparts, thus recapitulating the stiffening phenotype observed in T2D db/db mice. Given the above, we performed a set of follow-up experiments, in which we found that 1) exposure of endothelial cells or isolated mesenteric arteries from db/db mice to adropin reduces filamentous actin (F-actin) stress fibers and stiffness, 2) adropin-induced reduction of F-actin and stiffness in endothelial cells and db/db mesenteric arteries is abrogated by inhibition of nitric oxide (NO) synthase, and 3) stimulation of smooth muscle cells or db/db mesenteric arteries with a NO mimetic reduces stiffness. Lastly, we demonstrated that in vivo treatment of db/db mice with adropin for 4 wk reduces stiffness in mesenteric arteries. Collectively, these findings indicate that adropin can regulate arterial stiffness, likely via endothelium-derived NO, and thus support the notion that "hypoadropinemia" should be considered as a putative target for the prevention and treatment of arterial stiffening in obesity and T2D.NEW & NOTEWORTHY Arterial stiffening, a characteristic feature of obesity and type 2 diabetes (T2D), contributes to the development and progression of cardiovascular diseases. Herein we establish that adropin is decreased in obese and T2D models and furthermore provide evidence that reduced adropin may directly contribute to arterial stiffening. Collectively, findings from this work support the notion that "hypoadropinemia" should be considered as a putative target for the prevention and treatment of arterial stiffening in obesity and T2D.

Improved blood pressure and flow-mediated dilatation via increased plasma adropin and nitrate/nitrite induced by high-intensity interval training in patients with type 2 diabetes.

NEW FINDINGS: What is the central question of this study? Exercise training increases adropin and nitrite/nitrate (NOx) plasma levels in middle-aged and older healthy people. We hypothesized that high-intensity interval training may improve blood pressure and flow-mediated dilatation through the effects of adropin and NOx in patients of this age with type 2 diabetes. What is the main finding and its importance? High-intensity interval training may be more effective than moderate-intensity continuous training in improving endothelial function, blood pressure and flow-mediated dilatation through its effects on adropin and NOx in patients with type 2 diabetes. ABSTRACT: Adropin is a newly identified bioactive protein that is important in energy hemostasis and vascular endothelial function. Lower levels of adropin in patients with type 2 diabetes are related to coronary atherosclerosis, characterized by impaired flow-mediated dilatation (FMD). The purpose of the present study was to investigate FMD and plasma levels of adropin and nitrite/nitrate (NOx) in patients with type 2 diabetes at baseline and follow-up after 12 weeks of high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT). Sixty-six persons with type 2 diabetes were divided into HIIT, MICT, and control groups. The HIIT group intervention was 12 intervals (1.5 min) at 85-90% maximal heart rate (HRmax ) separated by 2 min at 55-60% HRmax in three sessions per week for 12 weeks. MICT training consisted of 42 min of cycling at 70% HRmax . Before and after the intervention, FMD was recorded with high-resolution Doppler ultrasound. Plasma levels of adropin and NOx were measured by enzyme-linked immunosorbent assay. After training FMD was significantly higher in the MICT and HIIT groups compared to the control group (P < 0.05). Plasma levels of adropin and NOx were higher in both exercise groups, but the increase was greater in the HIIT group (P < 0.01). Peak oxygen consumption was increased after exercise training in both groups compared to the control group (P < 0.01). Percentage FMD showed a positive correlation with plasma levels of adropin and NOx (both P < 0.01), and a negative correlation with diastolic blood pressure (r = -0.530, P = 0.035) and systolic blood pressure (r = -0.606, P = 0.013) in the HIIT group. The results indicate that HIIT improved FMD whilst increasing adropin, NOx and peak oxygen consumption. Increased plasma levels of adropin may contribute, in part, to blood pressure reduction by increasing nitric oxide production.

An association between adropin hormone and total testosterone in obese men: a case-control study.

BACKGROUND: Obesity is associated with low testosterone levels that could be caused by many mechanisms. Adropin, a peptide hormone, its levels are decreased in obesity and its receptors are expressed in the hypothalamus, the pituitary gland, and the testis. Adropin association to total testosterone in obese men is not detected yet. This study tries to find out possible associations between serum levels of adropin, adiponectin, total testosterone, and lipid profile in obese men. METHODS: Serum levels of adropin, adiponectin, total testosterone, and lipid profile parameters were measured in 43 obese men and 40 age-matched normal-weight men. RESULTS: Adropin, adiponectin, and testosterone levels were significantly lower in obese men versus normal-weight men. In all participants, positive correlations between adropin, adiponectin, and total testosterone were detected. Adropin is considered a predictor risk factor for testosterone. CONCLUSIONS: This study suggests a possible causal relationship between adropin and total testosterone which needs further investigation. TRIAL REGISTRATION: Clincialtrials.gov NCT03724825 , registered October 30th, 2018.

Regulation of Adropin by Sitagliptin monotherapy in participants with newly diagnosed type 2 Diabetes.

BACKGROUND: Adropin is a potent metabolic regulator of insulin sensitivity and glycolipid metabolism. The present study investigated the effects of sitagliptin on adropin and metabolic parameters in participants with newly diagnosed type 2 diabetes (T2D). METHODS: Thirty-five participants newly-diagnosed with T2D were prescribed sitagliptin 100 mg once daily for 17 weeks. Twenty-eight age-, sex-, and BMI-matched healthy subjects were included as the control group. Adropin and clinical parameters were assessed at baseline and after treatment. RESULTS: At baseline, serum adropin levels were lower in T2D participants than in the healthy individuals (3.12 ± 0.73 vs. 5.90 ± 1.22 ng/ml, P <  0.01). Serum adropin levels were significantly higher in T2D patients after sitagliptin treatment (4.97 ± 1.01 vs. 3.12 ± 0.73 ng/ml, P <  0.01). The changes in serum adropin levels after sitagliptin treatment were associated with the improvements of fasting blood glucose (FBG) (ß = - 0.71, P <  0.01), glycosylated hemoglobin (HbA1c) (ß = - 0.44, P <  0.01) and homeostatic model assessment of ß-cell function (HOMA-ß) (ß = 9.02, P <  0.01). CONCLUSIONS: Sitagliptin treatment could significantly increase serum adropin levels in participants with newly diagnosed T2D. The increase in serum adropin levels could be associated with the amelioration of glucose metabolism, which might be involved in beneficial glucose-lowering mechanisms of sitagliptin. TRIAL REGISTRATION: Clinicaltrials.gov , NCT04495881 . Retrospectively registered on 03/08/2020.

The role of adropin, HIF-1α and apelin biomarkers in the diagnosis of acute mesentaric ischemia.

OBJECTIVE: The absence of a specific biomarker for acute mesenteric ischemia diagnosis results in a delay in diagnosis and treatment, as well as a high mortality rate. The current research examined whether the proteins adropin, HIF-1α, and apelin may be used to help in the early detection of acute mesenteric ischemia. MATERIALS AND METHODS: A total of 20 patients with acute mesenteric ischemia, 20 patients with abdominal pain, and 20 healthy controls were included in the study. The levels of adropin, HIF-1, and apelin in the serum were determined using the ELISA method. RESULTS: Adropin concentrations were significantly higher in the acute mesenteric ischemia group than in the abdominal pain and healthy control groups (p < 0.05). HIF-1α levels were considerably greater in patients with acute mesenteric ischemia compared to both the abdominal pain group and the healthy control group (p < 0.05). There was no difference in apelin levels between the acute mesenteric ischemia and abdominal pain groups (p > 0.05). HIF-1α was found to be moderate (AUC: 0.705) and adropin was found to be a weak biomarker (AUC: 0.692) in the ROC analysis for acute mesenteric ischemia. CONCLUSION: In this study of 20 patients with acute mesenteric ischemia, we found adropin and HIF-1α levels to be increased compared to patients with abdominal pain who did not have acute mesenteric ischemia.

Maternal adropin levels in patients with gestational diabetes mellitus: a systematic review and meta-analysis.

BACKGROUND: Adropin is a regulatory protein with potential implications in energy homeostasis, glucose regulation, and insulin resistance. AIM: The aim of this meta-analysis was to compare the maternal serum/plasma adropin levels between gestational diabetes mellitus (GDM) patients and non-GDM controls. METHODS: Relevant studies were retrieved by online database and manual searching. The standardized mean differences (SMDs) with 95% confidence intervals (CIs) were obtained by a random-effects meta-analysis. A one-study leave-out sensitivity analysis and trimester-wise subgroup analysis were performed. RESULTS: A total of eight observations were included in this meta-analysis. The results based on random-effects meta-analysis indicated that adropin levels were significantly increased in GDM patients as compared to non-GDM controls (SMD = 2.41, 95% CI = 0.52-4.29, p= .01). The sensitivity analysis indicated that no single study had significantly influenced the overall outcome. CONCLUSIONS: The results indicate that maternal serum/plasma adropin concentrations were significantly higher in GDM patients as compared to non-GDM controls suggesting the potential associations of adropin in GDM. Despite this, further studies are needed to investigate the mechanistic, diagnostic and prognostic roles of trimester-wise adropin levels in GDM and associated fetal outcomes.

Diagnostic accuracy of adropin as a preliminary test to exclude acute pulmonary embolism: a prospective study.

BACKGROUND: This study aims to investigate the diagnostic accuracy of adropin as a biomarker to exclude the diagnosis of acute pulmonary embolism (PE). METHODS: Patients admitted to the emergency department of a tertiary health centre between August 2019 and August 2020 and diagnosed with PE were included in this prospective cohort study. The amount of serum adropin was determined in patients with (PE) and compared with that of healthy volunteers. Receiver operating characteristic analysis was performed with the obtained data, and the area under the curve (AUC) with a 95% confidence interval was determined. The parameters of diagnostic accuracy for PE were determined. RESULTS: A total of 57 participants were included in the study (28 controls and 29 PE patients). The mean adropin level in the PE group was 187.33 ± 62.40 pg/ml, which was significantly lower than that in the control group (524.06 ± 421.68 pg/ml) (p < 0.001). When the optimal adropin cut-off value was 213.78 pg/ml, the likelihood ratio of the adropin test was 3.4, and the sensitivity of the adropin test at this value was 82% with specificity of 75% (95% CI; AUC: 0.821). CONCLUSION: Our results suggest that adropin may be considered for further study as a candidate marker for the exclusion of the diagnosis of PE. However, more research is required to verify and support the generalizability of our study results.

Adropin's Role in Energy Homeostasis and Metabolic Disorders.

Adropin is a novel 76-amino acid-peptide that is expressed in different tissues and cells including the liver, pancreas, heart and vascular tissues, kidney, milk, serum, plasma and many parts of the brain. Adropin, encoded by the Enho gene, plays a crucial role in energy homeostasis. The literature review indicates that adropin alleviates the degree of insulin resistance by reducing endogenous hepatic glucose production. Adropin improves glucose metabolism by enhancing glucose utilization in mice, including the sensitization of insulin signaling pathways such as Akt phosphorylation and the activation of the glucose transporter 4 receptor. Several studies have also demonstrated that adropin improves cardiac function, cardiac efficiency and coronary blood flow in mice. Adropin can also reduce the levels of serum triglycerides, total cholesterol and low-density lipoprotein cholesterol. In contrast, it increases the level of high-density lipoprotein cholesterol, often referred to as the beneficial cholesterol. Adropin inhibits inflammation by reducing the tissue level of pro-inflammatory cytokines such as tumor necrosis factor alpha and interleukin-6. The protective effect of adropin on the vascular endothelium is through an increase in the expression of endothelial nitric oxide synthase. This article provides an overview of the existing literature about the role of adropin in different pathological conditions.

Daily Treatment of Mice with Type 2 Diabetes with Adropin for Four Weeks Improves Glucolipid Profile, Reduces Hepatic Lipid Content and Restores Elevated Hepatic Enzymes in Serum.

Adropin is a peptide hormone encoded by Energy Homeostasis Associated gene. Adropin modulates energy homeostasis and metabolism of lipids and carbohydrates. There is growing evidence demonstrating that adropin enhances insulin sensitivity and lowers hyperlipidemia in obese mice. The aim of this study was to investigate the effects of daily administration of adropin for four weeks in mice with experimentally induced type 2 diabetes (T2D). Adropin improved glucose control without modulating insulin sensitivity. Adropin reduced body weight, size of adipocytes, blood levels of triacylglycerol and cholesterol in T2D mice. T2D mice treated with adropin had lower liver mass, reduced hepatic content of triacylglycerol and cholesterol. Furthermore, adropin attenuated elevated blood levels of hepatic enzymes (ALT, AST, GGT and ALP) in T2D mice. In T2D mice, adropin increased the circulating adiponectin level. Adropin had no effects on circulating insulin and glucagon levels and did not alter pancreatic islets morphology. These results suggest that adropin improves glucose control, lipid metabolism and liver functions in T2D. In conjunction with reduced lipid content in hepatocytes, these results render adropin as an interesting candidate in therapy of T2D.

Novel Biomolecules in the Pathogenesis of Gestational Diabetes Mellitus 2.0.

Gestational diabetes mellitus (GDM) has become a major public health problem and one of the most discussed issues in modern obstetrics. GDM is associated with serious adverse perinatal outcomes and long-term health consequences for both the mother and child. Currently, the importance and purposefulness of finding a biopredictor that will enable the identification of women with an increased risk of developing GDM as early as the beginning of pregnancy are highly emphasized. Both "older" molecules, such as adiponectin and leptin, and "newer" adipokines, including fatty acid-binding protein 4 (FABP4), have proven to be of pathophysiological importance in GDM. Therefore, in our previous review, we presented 13 novel biomolecules, i.e., galectins, growth differentiation factor-15, chemerin, omentin-1, osteocalcin, resistin, visfatin, vaspin, irisin, apelin, FABP4, fibroblast growth factor 21, and lipocalin-2. The purpose of this review is to present the potential and importance of another nine lesser known molecules in the pathogenesis of GDM, i.e., 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF), angiopoietin-like protein-8 (ANGPTL-8), nesfatin-1, afamin, adropin, fetuin-A, zonulin, secreted frizzled-related proteins (SFRPs), and amylin. It seems that two of them, fetuin-A and zonulin in high serum levels, may be applied as biopredictors of GDM.

Inflammation Markers in Infants of Mothers with Gestational Diabetes.

AimPentraxin-3, high sensitive CRP (HsCRP) and adropin were investigated in cord blood of infants of mothers with gestational diabetes mellitus (IDM) to evaluate the exposure of fetus to inflammation and whether there is any correlation with clinical findings.MethodsForty IDM and forty three infants whose mother did not have diabetes were included in this prospective study. Adropin, pentraxin-3 and HsCRP levels were measured in the cord blood samples. Echocardiographic measurements were performed in the first three days of life.ResultsAdropin and pentraxine-3 levels were significantly lower and HsCRP levels were significantly higher in IDM group. Echocardiographic measurements of myocardial hypertrophy were negatively correlated with adropin.ConclusionAlterations in these markers in IDM supports the hypothesis of in utero fetal exposure to inflammation caused by gestational diabetes mellitus. Potentially, cord blood adropin might be used as a predictor for complications of diabetes.

Evaluation of the relationship between vitamin D level and adropin, IL-1ß, IL-6, and oxidative status in women.

BACKGROUND: Vitamin D, adropin, proinflammatory cytokines, and oxidative stress closely related with metabolic homeostasis and endothelial dysfunction. The aim of the present study is to investigate how vitamin D levels affect serum adropin, IL-1ß, IL-6, and oxidative stress. METHODS: A total of 77 female subjects were divided into 3 groups according to vitamin D levels. Biochemical parameters, adropin, IL-1ß, IL-6, oxidative stress markers were studied in these groups, and the results were compared statistically. RESULTS: Serum adropin, IL-1ß, IL-6, total oxidant status (TOS) and total antioxidant status (TAS) and oxidative stress index (OSI) levels differed significantly between the vitamin D groups (p < 0.05). A significant positive correlation was detected between vitamin D, and adropin and TAS (r = 0.807; p < 0.001, r = 0.814; p < 0.001, respectively). A significant negative correlation was detected between vitamin D, and IL-1ß, IL-6, TOS, OSI (r = -0.725; p < 0.001, r = -0.720; p < 0.001, r = -0.238; p = 0.037, r = -0.705; p < 0.001, respectively). DISCUSSION: Vitamin D could show its effects through vitamin D receptors on tissues or on the ENHO gene in adropin secreting tissues via direct or indirect mechanisms. Proinflammatory cytokines, oxidative stress, and adropin targeted studies could contribute to the prevention and treatment of diseases associated with vitamin D deficiency in future.