neuropeptide-y and Sleep-Apnea--Obstructive

Sleep disorders are a complicated and major public health concern affecting millions of individuals. Obstructive sleep apnoea (OSA) is a common but still under-recognized disease which can cause intermittent nocturnal hypercapnia. Neuropeptides play critical roles in neurotransmission, acting as transmitters or modulators. Results from recent studies have implicated several neuropeptides in sleep and breathing regulation, including orexin, neuropeptides Y and galanin. Therefore, the present study aimed to evaluate the influence of hypercapnia on these neuropeptides and their receptors in order to assess their potential role in the pathogenesis of OSA.. Fifteen C57BL/6J mice were randomly divided into three groups and exposed to moderate hypercapnia (5% CO(2) with balanced room air), or severe hypercapnia (10% CO(2) with balanced room air) or room air for 3 h (9:00-12:00 h), respectively. Immediately following exposure the brainstem and hypothalamus were excised for real-time reverse transcription polymerase chain reaction and western blot analyses.. In the hypothalamus gene expression including galanin, orexin and neuropeptide Y receptor 1 (NPYR1) was downregulated by hypercapnia. However, protein and mRNA levels of orexin-A receptor were upregulated by severe hypercapnia. In the brainstem only NPYR1 mRNA expression was decreased in moderate hypercapnia compared with that in severe hypercapnia.. These findings suggest that hypercapnia can affect these neuropeptides and their receptors, especially the orexin and orexin-A receptor. The potential relationships between these peptides and OSA are worthy of further investigation.

Topics: Animals; Blotting, Western; Brain; Brain Stem; Galanin; Hypercapnia; Hypothalamus; Intracellular Signaling Peptides and Proteins; Male; Mice; Mice, Inbred C57BL; Neuropeptide Y; Neuropeptides; Orexins; Real-Time Polymerase Chain Reaction; Receptors, Neuropeptide; Sleep; Sleep Apnea, Obstructive

Obstructive sleep apnea (OSA) is prevalent in 7.5% in urban Asian Indians. Peroxisome proliferator activated receptor gamma2 (PPARγ2) has been implicated in adipocyte differentiation. Neuropeptide Y (NPY) is also considered as a candidate gene for excess body fat accumulation. The association of PPARγ2 (Pro12Ala)} and NPY (Leu7Pro) gene polymorphisms with OSA has not been studied in Asian Indians.. To study the distribution of PPARγ2 (Pro12Ala) and NPY (Leu7Pro) polymorphism in Asian Indians with and without OSA.. This study was carried out in 252 obese subjects [(body mass index (BMI > 25 kg/m2]; 142 with OSA and 110 without OSA. Measurements included anthropometric and biochemical parameters (fasting blood glucose, lipid profile, various circumferences and skin-fold thicknesses). PPARγ2 (Pro12Ala) and NPY (Leu7Pro) gene} polymorphisms were studied in all subjects. The frequency of the variant allele (Ala12) of PPARγ2 gene was significantly higher in subjects with OSA (14.4%) when compared with subjects without OSA (5.5%; χ2= 9.7; p = 0.001). The distribution of the variant allele (Pro7) of NPY gene was comparable in subjects with OSA (3.5%) and without OSA (3.6%; χ2= 0.001, p = 0.94).. This study reveals a significantly higher frequency of PPARγ2 (Ala12) allele in obese Asian Indians with OSA when compared to obese Asian Indians without OSA.

Topics: Adult; Blood Glucose; Female; Genetic Association Studies; Genotype; Humans; India; Lipids; Male; Middle Aged; Mutation, Missense; Neuropeptide Y; Obesity; Polymorphism, Genetic; PPAR gamma; Sleep Apnea, Obstructive; Sleep Stages

Understanding the etiologic mechanisms underlying impaired glucose tolerance in obstructive sleep apnea (OSA) would assist development of therapies against this comorbidity. We hypothesized that in patients with OSA impaired glucose tolerance (IGT) would be associated with elevated levels of hormones associated with appetite regulation (leptin, ghrelin, neuropeptide Y [NPY] and peptide tyrosine-tyrosine [PYY]).. We studied 68 OSA patients (mean AHI 22 events/h) and 37 age and weight matched healthy controls recruited by advertisement. All participants received a standardized evening meal, attended polysomnography and an oral glucose tolerance test (OGTT) on waking. Hormones were measured in blood taken before sleep (22:30) and at the start of the OGTT.. Impaired glucose tolerance was present in 54% of patients and 32% of controls (p = 0.05). The only differences between groups was that leptin was significantly higher at 22:30 in OSA patients compared to controls (9.6 ng/L vs 7.9 ng/L, p = 0.05). OSA patients had marginally elevated plasma NPY levels at 22:30 (56.6 [52, 67] pmol/L vs 51.1[47.3, 61] pmol/L; p = 0.04). No differences in ghrelin, PYY or NPY were observed between patients with IGT and those without. However OSA patients with IGT had significantly higher value of leptin at both 22:30 (10.9 [7.7, 15.9] ng/mL vs 7.4 [5.6, 12.3] ng/mL, p = 0.02) and 07:00 (11.6 [7.6, 16.2] ng/mL vs 6.9 [5.4, 12.6] ng/mL, p = 0.024) than those without. In multivariate analysis the only major association of leptin was body mass index.. Clinically significant abnormalities of appetite regulating hormones are not present in OSA. Appetite regulating hormones did not differ in OSA patients with and without impaired glucose tolerance.

Topics: Blood Glucose; Dipeptides; Ghrelin; Glucose Intolerance; Glucose Tolerance Test; Humans; Leptin; Middle Aged; Neuropeptide Y; Risk Factors; Sleep Apnea, Obstructive

Resistant hypertension is always fount to be accompanied with obstructive sleep apnea syndrome (OSAS). Previous studies assumed inflammation participated in OSAS and hypertension. The fact that tumor necrosis factor a (TNF-alpha) was related to OSAS, while neuropeptide Y (NPY) was related to hypertension, was widely reported separately. To investigate the involvement of TNF-alpha and NPY simultaneously in hypertension accompanied with OSAS, 417 subjects who underwent the polymonograph and blood pressure measurement were consecutively selected. Plasma TNF-alpha and NPY levels were determined in normotensive with OSAS (n = 113), hypertensive without OSAS (n = 73), hypertensive with OSAS (n = 134), and those of controls (n = 97), respectively. A significant increase of plasma TNF-alpha and NPY were both observed in hypertensive subjects with or without OSAS, the highest level of TNF-alpha and NPY were in hypertension with the OSAS group. TNK-alpha, NPY, and neck circumference contributed to OSAS and hypertension as risk factors in the logistic regression model. Neck circumference was impacted by apnea/hyponea index, mean diastolic blood pressure, and TNF-alpha level, which was indicated via the multiple linear model. The present study indicated a positive interplay between plasma TNF-alpha, NPY, hypertension, and OSAS in the Han population of Xinjiang. Although there is evidence that inflammation plays a role in the pathophysiology of hypertension and OSAS, clear evidence is still lacking, and raises the dilemma of the hen and the egg. Further studies are needed to clarify the role of inflammation in the pathogenesis of hypertension with OSAS, in which neck size should be considered as a linked independent factor.

Topics: Adult; Case-Control Studies; Female; Humans; Hypertension; Inflammation Mediators; Male; Middle Aged; Neck; Neuropeptide Y; Risk Factors; Sleep Apnea, Obstructive; Tumor Necrosis Factor-alpha

To explore the potential role of neuropeptide Y (NPY) in the pathophysiological process of hypertension caused by obstructive sleep apnea syndrome (OSAS).. The concentration of serum NPY were measured with radioimmunoassay (RIA) in 417 subjects (97 normotensive controls without OSAS, 113 cases of normotensive with OSAS, 73 cases of hypertensive without OSAS and 134 cases of hypertensive with OSAS. Further, the mean NPY level were compared in four groups and the possible effective factors on NPY were discussed.. (1) The concentration of NPY in four groups were (50.5 +/- 37.2) pmol/L in normal controls, (76.0 +/- 39.9) pmol/L in normotensive with OSAS group, (66.9 +/- 36.2) pmol/L in hypertensive without OSAS group and (86.8 +/- 36.8) pmol/L in hypertensive with OSAS group. Whether the patients with OSAS combined with hypertension or not, the concentration of NPY in the serum raised remarkably compared with those without OSAS and hypertension, the highest level of serum NPY was detected in OSAS combined with hypertension group. (2) Pearson correlation analysis indicated that both SBP and DBP related to the serum NPY significantly in non-OSAS group (AHI <10), while the BMI, abdominal circumference, AHI as well as the lowest level of SaO2 correlated to NPY besides SBP in OSAS group with (AHI > or =10). (3) Multiple linear regression model showed that the abdominal circumference and AHI were contributing factors to SBP, while neck circumference and BMI were contributing factors to DBP. The level of NPY in the serum were significantly affected by AHI and BMI, in which the former one had greater influence.. The increased level of serum NPY may play weakly potential roles in the pathophysiological process of hypertension caused by OSAS.

Topics: Adult; Blood Pressure; Case-Control Studies; Female; Humans; Hypertension; Male; Middle Aged; Neuropeptide Y; Obesity; Sleep Apnea, Obstructive

Neuropeptide Y (NPY) and leptin are two peptides involved in the regulation of body weight, energy balance, and sympathetic tone. This study investigates the independent role of apneas and obesity on NPY and leptin plasma levels in patients with obstructive sleep apnea syndrome (OSAS). To this end we compared their values in 23 obese (body mass index > 30 kg/m2) and 24 nonobese (body mass index < 27 kg/m2) patients with OSAS, and in 19 obese and 18 nonobese control subjects without OSAS. Patients who used continuous positive airway pressure for more than 4 hours/night were reexamined 3 and 12 months later. We found that NPY levels were increased (p < 0.01) in patients with OSAS independently of obesity. Leptin levels were also increased in OSAS but this was mostly associated to obesity. Continuous positive airway pressure treatment reduced NPY levels in all patients and leptin levels only in nonobese patients (p < 0.01). We concluded that NPY and leptin plasma levels are increased in patients with OSAS. Yet, whereas the former appear independent of obesity, the latter are mostly associated with obesity.

Topics: Analysis of Variance; Biomarkers; Case-Control Studies; Continuous Positive Airway Pressure; Humans; Leptin; Male; Middle Aged; Neuropeptide Y; Obesity; Prospective Studies; Sleep Apnea, Obstructive; Statistics, Nonparametric