Apelin

The inductions of chronic diseases and neurodegeneration have become a major concern in various countries in the developed and developing world. Central co-ordination and homeostasis of neuroendocrine systems and renin-angiotensin systems (RAS) are influenced by external stressors, diet and lifestyles that lead to abnormal nitric oxide and neural pathways, appetite dysregulation and organ disease. The alteration in circadian photic signals in the neuroendocrine system involve the hypothalamus and the suprachiasmatic nucleus that are linked to apelinergic dysregulation associated with appetite disorders and various organ diseases. The peripheral sink amyloid beta hypothesis indicates that amyloid beta (Aβ) is rapidly removed by the liver and chronic diseases are connected to apelinergic dysfunction with abnormal amyloidogenic pathways. Environmental pollutants associated with unhealthy nutritional habits increase xenobiotics in plasma and may further promote neuroendocrine disease, kidney disease and non alcoholic fatty liver disease (NAFLD) with poor Aβ metabolism. Furthermore stress and unhealthy nutritional lifestyles increase oxidative stress with abnormal apelin and RAS regulation associated with poor nitric oxide and vascular Aβ metabolism with the acceleration of neuroendocrine diseases that include obesity, diabetes, cardiovascular disease and neurodegenerative diseases.

Background: This research investigated the symbiotic supplement influences on serum glycemic indices and lipids
as well as apelin rates and obesity values in polycystic ovary syndrome (PCOS) patients.
Materials and Methods: A total of 68 obese or overweight patients (20-44 years old) with PCOS were enrolled to
conduct a randomized double-blinded placebo-controlled clinical trial. A total of 34 people in the synbiotic group received
a synbiotic supplement and 34 people in the placebo group received placebo, daily for 8 weeks. Fasting blood
specimens, anthropometric measurements and dietary intake data were gathered three times during the study. The
information was analyzed by independent t test, paired t test, analysis of covariance and chi-square test.
Results: Synbiotic supplementation significantly decreased serum fasting glucose (P=0.02), insulin (P=0.001), homeostatic
model assessment for insulin resistance (IR, P=0.001), weight (P=0.02), body mass index (BMI, P=0.02),
waist circumference (WC, P=0.01), hip circumference (HC, P=0.02), and waist-to-height ratio (WHtR, P=0.02) but
significantly increased high-density lipoprotein (HDL) cholesterol (P=0.02) compared to the placebo. At the end of the
trial, no significant differences were seen in serum total cholesterol, triglyceride (TG), low-density lipoprotein (LDL)
cholesterol, or apelin levels as well as waist-to-hip ratio (WHR) between the two groups.
Conclusion: Synbiotic supplementation improved glycemic indices, lipid profile and obesity values in women
with PCOS. These beneficial effects were not related with alterations in serum apelin levels (Registration number:
IRCT20100408003664N19).

Strength exercise is a strategy applied in sports and physical training processes. It may induce skeletal muscle hypertrophy. The hypertrophy is dependent on the eccentric muscle actions and on the inflammatory response. Here, we evaluate the physiological, immunological, and inflammatory responses induced by a session of strength training with a focus on predominance of the eccentric muscle actions. Twenty volunteers were separated into two groups: the untrained group (UTG) and the trained group (TG). Both groups hold 4 sets of leg press, knee extensor, and leg curl at 65% of personal one-repetition maximum (1RM), 90 s of recovery, and 2″conc/3″eccen of duration of execution in each repetition. Blood samples were collected immediately before and after, 2 hours after, and 24 h after the end of the exercise session. The single session of strength training elevated the heart rate (HR), rating of perceived exertion (RPE), visual analog scale (VAS), and lactate blood level in UTG and TG...

The aim of this study was to investigate the plasma apelin levels in diabetic patients with and without neuropathy. All consecutive diabetic patients who presented for routine follow-up at our outpatient clinic were invited to participate in this clinical study. Forty diabetic patients (20 female and 20 male) and twenty-two non-diabetic control subjects (9 female and 13 male) were included in the study. Neurological evaluations in diabetic subjects were done by nerve conduction studies and evaluated with the Neuropathy Symptom Score. Fasting plasma glucose, HbA1c, lipid and apelin levels were measured in each subject. The mean plasma apelin level was signifiantly higher in the diabetic patients than in the control subjects (p = 0.026). Apelin levels were statistically similar between diabetic patients with and without neuropathy (p = 0.43). Further, plasma apelin levels were found to be higher in diabetic patients with neuropathy when compared with those of healthy control subjects (p = 0.02). In diabetic patients with neuropathy, plasma apelin levels correlated signifiantly with diabetes duration (r=0.5, p = 0.02). We propose that apelin levels in diabetic patients are higher in the presence of neuropathy and longer disease duration, although this might not solely suffie as an indicator for the presence of neuropathy in diabetic patients. Drawing attention to the possible association between the apelinergic system and diabetes mellitus, we believe that further studies with larger samples should be carried out also to investigate the presence of retinopathy and nephropathy.

Strength exercise is a strategy applied in sports and physical training processes. It may induce skeletal muscle hypertrophy. The hypertrophy is dependent on the eccentric muscle actions and on the inflammatory response. Here, we evaluate the physiological, immunological, and inflammatory responses induced by a session of strength training with a focus on predominance of the eccentric muscle actions. Twenty volunteers were separated into two groups: the untrained group (UTG) and the trained group (TG). Both groups hold 4 sets of leg press, knee extensor, and leg curl at 65% of personal one-repetition maximum (1RM), 90 s of recovery, and 2conc/3eccen of duration of execution in each repetition. Blood samples were collected immediately before and after, 2 hours after, and 24 h after the end of the exercise session. The single session of strength training elevated the heart rate (HR), rating of perceived exertion (RPE), visual analog scale (VAS), and lactate blood level in UTG and TG. ...

Background and Objectives: Previous studies have shown that morphine dependence leads to myocardial dysfunction. In addition, apelin plays a protective role in cardiac function. The purpose of this study was to evaluate effects of morphine dependence and three models of exercise training on serum apelin level of dependent and healthy rats. Methods: Ten healthy and 40 morphine-dependent rats were used in this study. The morphine-dependent rats were divided into four equal groups of control addicts, endurance training, strength training and concurrent training. The training exercises were carried out for eight weeks, five days a week. Serum apelin level was measured by ELISA, 72 hours after the last training session. Results: Statistical analysis demonstrated that apelin level increased significantly in morphine-dependent rats compared to healthy controls. On the other hand, endurance and concurrent training significantly increased serum apelin level in morphine-dependent rats compared to control addicts, but strength training had not effect on serum apelin level in morphine-dependent rats. Conclusion: Endurance and concurrent training may have cardioprotective effects on morphine-dependent rats by increasing serum apelin levels. Therefore, such training activities could be recommended to morphine-dependent patients to prevent cardiac disorders.

In skeletal muscle, new functions for vessels have recently emerged beyond oxygen and nutrient supply, through the interactions that vascular cells establish with muscle stem cells. Here, we demonstrate in human and mouse that endothelial cells (ECs) and myogenic progenitor cells (MPCs) interacted together to couple myogenesis and angiogenesis in vitro and in vivo during skeletal muscle regeneration. Kinetics of gene expression of ECs and MPCs sorted at different time points of regeneration identified three effectors secreted by both ECs and MPCs. Apelin, Oncostatin M, and Periostin were shown to control myogenesis/angiogenesis coupling in vitro and to be required for myogenesis and vessel formation during muscle regeneration in vivo. Furthermore, restorative macrophages, which have been previously shown to support myogenesis in vivo, were shown in a 3D triculture model to stimulate myogenesis/angiogenesis coupling, notably through Oncostatin M production. Our data demonstrate that ...

Apelin is an adipokine directly associated with adiposity, insulin resistance, and decreased blood pressure. Urinary 8-isoprostane is a marker of chronic oxidative endothelial stress. Visfatin, an adipokine that acts by binding and activating the insulin receptor, has been associated with hypertension. As severe hypertension (SH) is highly prevalent among African Americans (AA), we aimed to assess the association of these biomarkers with SH status. A sample of 250 AA participants (134 normotensive controls and 116 with SH (including 98 treatment controlled, SCH: severe controlled hypertension, and 18 treatment resistant, SRH: severe resistant hypertension)) from the Minority Health Genomics and Translational Research Bio-Repository Database (MH-GRID) in metro Atlanta had blood analyzed for apelin and visfatin and urine for 8-isoprostane. T-tests, sex-specific age-adjusted correlation coefficients, and multivariable logistic regression models were used to assess the association of bi...

Apelin receptor (APJR) is a key regulator of human cardiovascular function and is activated by two different endogenous peptide ligands, apelin and Elabela, each with different isoforms diversified by length and amino acid sequence. Here we report the 2.6-Å resolution crystal structure of human APJR in complex with a designed 17-amino-acid apelin mimetic peptide agonist. The structure reveals that the peptide agonist adopts a lactam constrained curved two-site ligand binding mode. Combined with mutation analysis and molecular dynamics simulations with apelin-13 binding to the wild-type APJR, this structure provides a mechanistic understanding of apelin recognition and binding specificity. Comparison of this structure with that of other peptide receptors suggests that endogenous peptide ligands with a high degree of conformational flexibility may bind and modulate the receptors via a similar two-site binding mechanism.

Background and Aims Apelin is a newly discovered adipokine whose level is high in obese people with insulin resistance. It is not clear how endurance training affects apelin plasma levels. The present study aims to investigate the plasma levels of apelin-13, insulin, and glucose in obese male rats following 12 weeks of endurance training. Methods Samples were 14 obese male Wistar rats who received high-fat food for eight weeks to become fat based on the Lee obesity Index. The rats were then randomly divided into control (n=7) and training (n=7) groups. The training group ran on a treadmill with zero slope for 12 weeks, 5 days per week (60-min sessions at a speed of 15-30 meters per minute). The ELISA method was used for measuring the levels of apelin-13 and insulin, while photometric glucometer was used measuring the glucose level. Results The results of independent t-test showed that there was a significant difference between plasma levels of glucose (P=0.0001), insulin (P=0.0001) and apelin (P=0.041) in obese male rats of control group and endurance test. The results of independent t-test showed a significant difference in plasma levels of glucose, insulin, and apelin-13 between the two groups (P<0.05). The glucose and insulin levels in the training group were lower than in the control group , while the apelin-13 level was higher in the training group. Pearson correlation test results showed no significant relationship between levels of apelin-13 and insulin (P=0.07) as between apelin-13 and glucose (P=0.055) after 12 weeks of endurance training. Conclusion It seems that 12 weeks of endurance training can reduce the plasma levels of insulin and glucose and increase the plasma level of apelin-13 in obese male rats.