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BACKGROUND Polycystic ovary syndrome (PCOS) is a common female reproductive-age endocrine disease predominantly characterized by chronic anovulation, hyperandrogenism, insulin-resistance and low-grade inflammatory status. Exercise training (ET) favourably modulates cardiopulmonary function and insulin-sensitivity markers in PCOS women. The present study investigated the effects of ET on autonomic function and inflammatory pattern in PCOS women. STUDY DESIGN Prospective baseline uncontrolled clinical study. METHODS One-hundred and eighty five PCOS women referred to our department were screened for the inclusion into the study protocol from March 2004 to July 2007. One-hundred and twenty four PCOS women met the criteria for the inclusion into the study protocol and were subdivided into two groups each composed of 62 patients: PCOS-T (trained) group underwent 3-month ET program, whereas PCOS-UnT (untrained) group did not. At baseline and at 3-month follow-up, hormonal and metabolic profile, cardiopulmonary parameters, autonomic function (as expressed by heart rate recovery, HRR) and inflammatory pattern [as expressed by C-reactive protein (CRP) and white blood cells (WBCs) count] were evaluated. RESULTS PCOS-T showed a significant (P < 0.05) improvement in maximal oxygen consumption (VO(2max)) and in post-exercise HRR, and a significant (P < 0.001) decrease in CRP and WBCs; whereas no statistically significant changes of the same parameters were observed in PCOS-UnT. Multiple linear regression analysis showed that 3-month HRR is linearly related to the inclusion in training group (beta = 0.316, P < 0.001), VO(2max) (beta = 0.151, P = 0.032) and the ratio between glucose and insulin area under curve (AUC) (beta = 0.207, P = 0.003), and inversely related to body mass index (beta = -0.146, P = 0.046), insulin AUC (beta = -0.152, P = 0.032), CRP (beta = -0.165, P < 0.021), and WBCs count (beta = -0.175, P = 0.039). CONCLUSIONS Exercise training improves autonomic function and inflammatory pattern in PCOS women.

Recent studies have demonstrated that obesity is a significant risk factor for the development of several malignancies such as cancer. Colorectal cancer is among the most common cancers worldwide and is strong linked to obesity. A healthy lifestyle, characterized by hypocaloric diet and physical activity, is important to reduce a chronic inflammation, oxidative stress and metabolic disorders typical of obesity (Messina et al, 2018; Messina et al, 2017; Messina et al, 2015). It is well known that the chronic inflammation state and oxidative stress are responsible for the aging and development of many diseases, such as cancer. Dysregulation of cytokine's secretion probably participates in the establishment of cancer in obese patients. The aim of this study is to analyse the effects of sera from obese patients subjected to a physical activity program before and after weight loss on cell viability, apoptosis and oxidative stress in HCT116 carcinoma cell line treated for 24, 48 and 72 hours through MTT test. We analysed the expression of cytokines in HCT116 cells. We found that sera from obese after physical activity intervention compared to treatment with sera from obese patients before physical activity intervention reduce the survival rate of HCT116 cells through induction of apoptosis and oxidative stress. Finally, we found a reduction of mRNA levels corresponding to the pro-inflammatory IL-6 and IL-8 cytokines together with an increase of the anti-inflammatory IL-10 cytokine. We can conclude that the physical activity has numerous beneficial effects also in colorectal cancer cell, indeed the physical activity and weight loss in obese subjects have an inhibitory and anti-inflammatory effects in a short period on carcinoma cell line.

Emanuela Viggiano,1,2 Vincenzo Monda,1 Antonietta Messina,1 Fiorenzo Moscatelli,3 Anna Valenzano,3 Domenico Tafuri,4 Giuseppe Cibelli,3 Bruno De Luca,1 Giovanni Messina,1,3 Marcellino Monda1 1Department of Experimental Medicine, Section of Human Physiology and Unit of Dietetics and Sports Medicine, Second University of Naples, Naples, 2Department of Medicine, University of Padua, Padua, 3Department of Clinical and Experimental Medicine, University of Foggia, Foggia, 4Department of Motor Sciences and Wellness, University of Naples “Parthenope”, Naples, Italy Abstract: Depression of electrocorticogram propagating over the cortex surface results in cortical spreading depression (CSD), which is probably related to the pathophysiology of stroke, epilepsy, and migraine. However, preconditioning with CSD produces neuroprotection to subsequent ischemic episodes. Such effects require the expression or activation of several genes, including neuroprotective ones. Recently, it has been demonstrated that the expression of the uncoupling proteins (UCPs) 2 and 5 is amplified during brain ischemia and their expression exerts a long-term effect upon neuron protection. To evaluate the neuroprotective consequence of CSD, the expression of UCP-5 in the brain cortex was measured following CSD induction. CSD was evoked in four samples of rats, which were sacrificed after 2hours, 4hours, 6hours, and 24hours. Western blot analyses were carried out to measure UCP-5 concentrations in the prefrontal cortices of both hemispheres, and immunohistochemistry was performed to determine the localization of UCP-5 in the brain cortex. The results showed a significant elevation in UCP-5 expression at 24hours in all cortical strata. Moreover, UCP-5 was triggered by CSD, indicating that UCP-5 production can have a neuroprotective effect. Keywords: cortical spreading depression, neuroprotective effect, uncoupling protein-5

The orexin-A/hypocretin-1 and orexin-B/hypocretin-2 are neuropeptides synthesized by a cluster of neurons in the lateral hypothalamus and perifornical area. Orexin neurons receive a variety of signals related to environmental, physiological and emotional stimuli, and project broadly to the entire CNS. Orexin neurons are “multi-tasking” neurons regulating a set of vital body functions, including sleep/wake states, feeding behavior, energy homeostasis, reward systems, cognition and mood. Furthermore, a dysfunction of orexinergic system may underlie different pathological conditions. A selective loss orexin neurons was found in narcolepsia, supporting the crucial role of orexins in maintaining wakefulness. In animal models, orexin deficiency lead to obesity even if the consume of calories is lower than wildtype counterpart. Reduced physical activity appears the main cause of weight gain in these models resulting in energy imbalance. Orexin signaling promotes obesity resistance via enhanced spontaneous physical activity and energy expenditure regulation and the deficiency/dysfunction in orexins system lead to obesity in animal models despite of lower calories intake than wildtype associated with reduced physical activity. Interestingly, orexinergic neurons show connections to regions involved in cognition and mood regulation, including hippocampus. Orexins enhance hippocampal neurogenesis and improve spatial learning and memory abilities, and mood. Conversely, orexin deficiency results in learning and memory deficits, and depression.

Summary Objective Heart rate recovery (HRR) is a measure derived from exercise test, defined as the fall in heart rate during the first minute after maximal exercise. Abnormal HRR is a measure of autonomic dysfunction associated with an increased mortality. This study was performed to evaluate the HRR in polycystic ovary syndrome (PCOS). Design Prospective controlled clinical study. Patients Seventy-five PCOS women compared to 75 healthy women matched for age (21·7 ± 2·1 years vs. 21·9 ± 1·8 years, respectively) and body mass index (BMI) (29·0 ± 2·6 kg/m2 vs. 29·1 ± 2·9 kg/m2, respectively). Measurements Subjects were studied for their hormonal and metabolic profile, and underwent cardiopulmonary exercise test (CPX). Results PCOS women showed a significantly reduced HRR (12·9 ± 1·8 vs. 20·4 ± 3·1 beats/min, P

Menopause is a significant period characterized by physiological change. Hormonal changes are largely related to estrogen depletion and subsequent cessation of ovarian function. This study analyzed vegetative modulation, expressed as heart rate variability (HRV) power spectral analysis, resting energy expenditure, and body composition in women in post-menopause with and without hormone-replacement therapy (HRT). 87 Sedentary women were enrolled, 41 (age: 53-54) women with BMI of 21.6 ± 2.6 kg/m2 were on HRT and 46 (age: 52-63) with BMI of 22.4 ± 1.8 kg/m2 were not. This experiment marks aspects regarding the relationship between the autonomic nervous system and body weight in HRT and menopause.

This experiment tested the effect of a lesion of cerebral catecholaminergic neurons on the sympathetic and thermogenic effects induced by an intracerebroventicular (icv) injection of orexin A. The firing rates of the sympathetic nerves to the interscapular brown adipose tissue (IBAT), along with MAT, colonic temperatures and heart rate were monitored in urethane-anesthetized male Sprague-Dawley rats before an injection of orexin A (1.5 nmol) into the lateral cerebral ventricle and over a period of 150 min after the injection. Three days before the experiment, the rats were pre-treated with an icv injection of 6-hydroxydopamine (6-OHDA) or 6-OHDA plus desipramine or saline. The results show that orexin A increases the sympathetic firing rate, IBAT, colonic temperatures and heart rate in the rats pre-treated with saline. This increase is blocked by the pre-treatment with 6-OHDA alone or 6-OHDA plus desipramine. These findings indicate that cerebral catecholaminergic neurons (particularly the dopaminergic pathway) play a fundamental role in the complex reactions related to activation of the orexinergic system. (c) 2006 Elsevier B.V. All rights reserved.

Since no experiment regarding a possible relation between quetiapine and orexin A has been reported in international literature, this experiment tested the effect of quetiapine on the sympathetic and thermogenic effects induced by orexin A. The firing rates of the sympathetic nerves to interscapular brown adipose tissue (IBAT), along with IBAT, colonic temperatures and heart rate were monitored in urethane-anesthetized male Sprague-Dawley rats before an injection of orexin A (1.5 nmol) into the lateral cerebral ventricle and over a period of 150 min after the injection. The same variables were monitored in rats with an intraperitoneal administration of quetiapine (5 or 10 mg/kg bw), injected 30 min before the orexin administration. The results show that orexin A increases the sympathetic firing rate, IBAT, colonic temperatures and heart rate. This increase is delayed or reduced by the injection of quetiapine. These findings indicate that quetiapine affects the complex reactions related to activation of orexinergic system. Possible influences on the control of body weight and temperature are discussed.

Obesity is a public health disease and its incidence is steadily increasing both in adults and in children especially in the Western World. It is important to understand the underlying mechanisms of obesity and possible treatments as the orexin system with its receptors, which are involved in different physiological processes. In fact, the aim of this mini-review is to consider the importance of the orexin system and the role that orexin plays in the regulation of obesity and physical activity. Furthermore to demonstrate how the orexin and its receptors fit within a network distributed in multiple brain areas, each with specific actions, whose activation and interconnection has been seen to lead to a lower propensity for increase of fat mass, it could thus constitute an important future target for prevention and treatment of obesity.

Glucose uptake in skeletal muscle is dependent on the translocation of GLUT4 glucose transporters to the plasma membrane. The most important stimulators of glucose transport in skeletal muscle are insulin and exercise. Glucose uptake in skeletal muscle during exercise induces acceleration of many processes compared to the resting state. The scientific literature does not underline the role played by muscle contraction to increase glucose uptake with insulin-independent mechanisms. Search on Pub Med (May 05, 2015) using the key words "contraction and glucose uptake and muscle" gives 717 reports, while a search using the key words "insulin and glucose uptake and muscle" cites 5676 publications. The present paper describes the role of exercise in the muscle glucose uptake. Contraction of muscle induces GLUT4 translocation in the absence of insulin. There are different intracellular "pools" of GLUT4, one stimulated by insulin and another one stimulated by exercise. The roles exerted by AMPK, AICAR, calcium, NO, glycogen and hypoxia in the glucose uptake during exercise are emphasized. The effects of these phenomena on human wellness are reported.

This review of our literature describes the effects of many neuroleptic drugs on the sympathetic and hyperthermic reactions due to orexin A, a neuropeptide affecting body temperature and food intake by an increase in sympathetic activity. Haloperidol reduces, while clozapine and olanzapine block the hyperthermia induced by orexin A. Risperidone enhances the elevation of body temperature due to orexin A. Quetiapine delays these hyperthermic effects. The implications on human therapeutic strategies are discussed, including the involvement of orexinergic pathway in the induction of obesity, induced by these neuroleptic substances. We summarize our published data in a unique report so to emphasize the influences of these neuroleptic drugs on the control of body temperature, exerted by orexinergic system. This large vision could be also useful to address therapeutic choices. Patients with serious mental illness are at higher risk of developing metabolic abnormalities (e.g., weight gain, increased blood pressure, and glucose or lipid levels) in comparison to general population. Since the risk increases following initiation of narcoleptic therapy, it must assess carefully risks and benefits when choosing a particular antipsychotic drug.

The orexin-A and orexin-B are a hypothalamic neuropeptides, involved in the regulation of feeding behaviour, sleep-wakefulness rhythm, and neuroendocrine homeostasis that influence the sympathetic nervous system activity, blood pressure regulation, and metabolic status, glycemic, and may contribute to increase diabetics morbidity and mortality. This review concentrates on the catabolic role of orexin, which paradoxically coexists with its anabolic feeding-inducing role. This review aims to provide insight into the biological mechanism that controls orexin’s role in energy expenditure and to discuss its significance in the context of glycemic control. On the other hands, hypothalamus regulates muscle glucose metabolism and its insulin sensitivity; in fact the ventromedial hypothalamus increases glucose uptake in certain peripheral tissues, including brown adipose tissue. The circumstance that it has been found a relationship between brown adipose tissue, orexins, glucose, insulin levels suggests new research focused on the possible roles of orexins in many anomalies of energy expenditure and of glucose homeostasis, with reference to the diabetic patient.

It is extremely important for the health to understand the regulatory mechanisms of energy expenditure. These regulatory mechanisms play a central role in the pathogenesis of body weight alteration. The hypothalamus integrates nutritional information derived from all peripheral organs. This region of the brain controls hormonal secretions and neural pathways of the brainstem. Orexin-A is a hypothalamic neuropeptide involved in the regulation of feeding behavior, sleep-wakefulness rhythm, and neuroendocrine homeostasis. This neuropeptide is involved in the control of the sympathetic activation, blood pressure, metabolic status, and blood glucose level. This minireview focuses on relationship between the sympathetic nervous system and orexin-A in the control of eating behavior and energy expenditure. The "thermoregulatory hypothesis" of food intake is analyzed, underlining the role played by orexin-A in the control of food intake related to body temperature. Furthermore, the paradoxical eating behavior induced orexin-A is illustrated in this minireview.

Menopause is a period of significant physiological change that is largely related to estrogen depletion and subsequent cessation of ovarian function. During menopause period, women tend to gain weight and fat mass. It is not clear whether the increase in adiposity is a consequence of the decline in endogenous estrogen. Cardiovascular disease incidence increases with age in women as well as in men, but in women there is an additional increase due to the menopause. Many researches were conducted to assess the contribution of factors such as estrogen depletion, REE decline, and aging to weight gain. An increase in orexin-A plasma levels, paralleling lower estrogen levels, was found during menopause. The goal of this review is to provide insight into the biological mechanism governing orexin’s role in energy expenditure; autonomic nervous system and cardiovascular risk discuss its significance in the context of menopause. Orexins are hypothalamic neuropeptides recently discovered, involved in the regulation of feeding behaviour, sleepwakefulness rhythm, and neuroendocrine homeostasis. Orexins might offer the missing link between postmenopausal hypoestrogenism and other manifestations of the menopausal syndrome, including appetite and weight changes and increase in cardiovascular risk.

The resting energy expenditure and the adaptation of the autonomic nervous system induced by sport activities in sedentary women and in female professional basketball players have been studied. Resting energy expenditure, body composition and the level of activity of the autonomic nervous system were measured before and after a period of six months. The physical activity induced an increase in resting energy expenditure and free fat mass without variations in body weight. Basketball players showed a significant increase in the parasympathetic activity, measured by the power spectral analysis of the heart rate variability. These findings demonstrate that resting energy expenditure is higher in the athletes than in sedentary women, despite the augmented parasympathetic activity that is usually related to lower energy expenditure.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) have been reported to have subclinical cardiovascular disease (CVD) and increased abdominal fat. The aim of this study was to evaluate the relationship between visceral fat (VF) and early markers of CVD in PCOS women. METHODS: Two hundred overweight PCOS women [(mean +/- SD) age 24.6 +/- 3.2 years, body mass index (BMI) 28.5 +/- 2.8 kg/m2] and 100 healthy age- and BMI-matched volunteer controls entered this cross-sectional study. In all subjects, the amount of VF was measured by ultrasonography. Anthropometric measurements [BMI and waist circumference (WC)], complete hormonal and metabolic pattern, carotid intima-media thickness (IMT), brachial arterial flow-mediated dilation (FMD) and inflammatory biomarkers [C-reactive protein (CRP), fibrinogen, white blood cells count and plasminogen activated inhibitor-1] were also obtained from all subjects. A stepwise linear regression model was used in PCOS patients to verify if IMT or FMD as dependent variables are affected by other independent variables. RESULTS: VF amount was significantly (P < 0.001) higher in PCOS subjects than in healthy controls [31.4 +/- 7.3 versus 28.0 +/- 6.1 (mean+/-SD) mm, respectively] and directly related to insulin resistance: HOMA (r = 0.918, P < 0.001) and AUC(INS) (r = 0.879, P < 0.001), and to WC (r = 0.658; P < 0.001). In PCOS, the two linear regression analyses showed that IMT is positively affected by VF and CRP, whereas FMD is positively affected by IMT and negatively by VF and CRP. CONCLUSIONS: VF amount is associated with subclinical CVD in PCOS patients.

Since experiments regarding a possible relation between olanzapine and orexin A has been scarcely reported in international literature, this experiment tested the effect of olanzapine on the sympathetic and thermogenic effects induced by orexin A. The filing rates of the sympathetic nerves to interscapular brown adipose tissue (IBAT), along with IBAT, colonic temperatures and heart rate were monitored in urethane-anesthetized male Sprague-Dawley rats before an injection of orexin A (1.5 nmol) into the lateral cerebral ventricle and over a period of 150 min after the injection. The same variables were monitored in rats with an intraperitoneal administration of olanzapine (16 mg/kg bw), injected 30 min before the orexin administration. The results show that orexin A increases the sympathetic firing rate, IBAT, colonic temperatures and heart rate. This increase is blocked by the injection of olanzapine. These findings indicate that olanzapine affects the complex reactions related to activation of orexinergic system. (C) 2007 Elsevier Inc. All rights reserved.

Summary Objective The aim of the present study was to determine if the favourable cardiopulmonary and metabolic benefits induced by exercise training (ET) programme are maintained after its cessation. Patients Thirty-two young overweight polycystic ovary syndrome (PCOS) women matched for age and body mass index (BMI) with other 32 PCOS patients was enrolled. The first group [PCOS-T (trained)] underwent 24-week ET programme, whereas the second [PCOS-DT (detrained)] underwent 12-week ET programme followed by 12-week detraining period. Methods At baseline, after 12- and 24-week follow-up, all PCOS women were studied for their hormonal (ovarian and adrenal androgens), metabolic (glucose and insulin) and lipid profile, and underwent cardiopulmonary exercise test. Results After the initial 12-week ET programme, both PCOS-T and PCOS-DT groups, without differences between groups, showed a similar significant (P

Context: Polycystic ovary syndrome (PCOS) is an endocrine disease closely related to several risk factors for cardiovascular disease. An impaired cardiopulmonary functional capacity was previously demonstrated in PCOS women. No data regarding the effects of a structured exercise training (ET) program on cardiopulmonary functional capacity in PCOS women are available. Objective: Our objective was to evaluate the effects of a 3-month ET programoncardiopulmonaryfunctionalcapacityinyoungPCOSwomen. Design and Setting: A prospective baseline-randomized clinical study was conducted at the University “Federico II” of Naples, School of Medicine (Italy). Patients: Ninety young overweight PCOS women were enrolled. Mean Outcome Measures: Ninety young PCOS women were randomly subdivided into two groups, each composed of 45 subjects. The PCOS-T (trained) group underwent a 3-month structured ET program, whereas the PCOS-UnT (untrained) group did not. Hormonal and metabolic profiles and cardiopulmonary and exercise parameters were evaluated. Results: After 3-month ET, PCOS-T showed a significant improvement in peak oxygen consumption (35.4%; P 0.001) and in maximal workload (37.2%; P 0.001). In PCOS-T we also observed a significant reduction in body mass index (4.5%; P 0.001) and in C-reactive protein (10%; P 0.001), and a significant (P 0.001) improvement in insulin sensitivity indexes. After 3 months, no changes were observed in PCOS-UnT. Conclusions: A 3-month structured ET program improves cardiopulmonary functional capacity in young PCOS women. (J Clin Endocrinol Metab 92: 1379–1384, 2007)

OBJECTIVE: The aim of the present study was to investigate the potential alterations in electrocardiographic (ECG) pattern in patients with polycystic ovary syndrome (PCOS). PATIENTS: Fifty PCOS patients and 50 age- and body mass index-matched healthy women were studied. METHODS: We assessed hormonal and metabolic pattern, and performed ECG analysis for evaluating PQ interval, QRS duration, minimum and maximum QT interval corrected for heart rate (QT(c)min and QT(c)max, respectively), corrected QT dispersion (QT(c)d), corrected J point/T-wave interval (JTend(c)), corrected JTmax interval (JTmax(c)), and corrected Tmax-end interval (Tmax-end(c)). RESULTS: QT(c)min (399 +/- 21 vs. 396 +/- 25 ms, P = 0.51); QT(c) max (445 +/- 25 vs. 443 +/- 27 ms, P = 0.70); and QT(c)d (46 +/- 13 vs. 47 +/- 15 ms, P = 0.72); JTend(c) (337 +/- 14 vs. 336 +/- 16 ms(1/2), P = 0.74); and JTmax(c) (256 +/- 22 vs. 258 +/- 21 ms(1/2), P = 0.64); Tmax-end(c) (81 +/- 18 vs. 78 +/- 19 ms(1/2), P = 0.42) were not significantly different between PCOS and healthy women. CONCLUSION: Despite profound differences in hormonal and metabolic pattern, our data demonstrate no significant difference in ECG pattern in PCOS compared to healthy controls.