OBJECTIVE:Eating slowly increases the postprandial responses of some anorexigenic gut hormones in healthy lean subjects. As the rate of food intake is positively associated with obesity, the aim of the study was to determine whether eating the same meal at different rates evokes different postprandial anorexigenic responses in obese adolescent and adult subjects.DESIGN AND METHODS:Eighteen obese adolescents and adults were enrolled. A test meal was consumed on two different sessions by each subject, meal duration taking either 5  min (fast feeding) or 30  min (slow feeding). Circulating levels of glucagon-like peptide 1 (GLP1), peptide YY (PYY), glucose, insulin, and triglycerides were measured over 210  min. Visual analog scales were used to evaluate the subjective feelings of hunger and satiety.RESULTS:fast feeding did not stimulate GLP1 release in obese adolescent and adults, whereas slow feeding increased circulating levels of GLP1 only in obese adolescents. Plasma PYY concentrations increased both in obese adolescents and in adults, irrespective of the eating rate, but slow feeding was more effective in stimulating PYY release in obese adolescents than in adults. simultaneously, slow feeding evoked a higher satiety only in obese adolescents compared with fast feeding but not in obese adults. in obese adolescents, slow feeding decreased hunger (only at 210 min). irrespective of the eating rate, postprandial responses of insulin and triglycerides were higher in obese adults than in obese adolescents.CONCLUSION:Slow feeding leads to higher concentrations of anorexigenic gut peptides and favors satiety in obese adolescents, but this physiological control of food intake is lost in obese adults.

Repetition of voluntary exercise bouts and of different pharmacological GH-releasing stimuli at 2-h intervals is associated with a complete abolishment of GH responsiveness. By contrast, a different pattern is observed after repeated neuromuscular electrostimulation, which is characterized by preservation of GH responsiveness. Aim of the study was to evaluate GH responses to repeated bouts of respiratory muscle endurance training (RMET) by mean of a specific commercially available device (Spiro Tiger®). Eight healthy men underwent an incremental progressive RMET protocol of 11 daily sessions. Blood samplings for GH, cortisol and lactate (LA) determinations were collected during the 12th session, which was composed of two consecutive bouts of RMET (of identical intensity and duration: 1 min at a respiration rate of 28 acts/min, 5 min at 32 acts/min, 5 min at 34 acts/min, 4 min at 36 acts/min) at a 2 h interval. Baseline GH levels (mean: 0.9±0.4 ng/ml) significantly (p<0.01) increased after the first bout of RMET (peak: 15.7±4.0 ng/ml). The administration of the second bout of RMET resulted in a significantly lower (p<0.05) GH increase (peak: 3.9±0.8 ng/ml) in comparison with the first one. Baseline LA levels (mean: 1.2±0.1 mmol/l) significantly increased (p<0.001) after the first bout of RMET (peak: 2.3±0.2 mmol/l). The administration of the second RMET bout resulted in a comparable LA increase (from a basal value of 1.2±0.1 mmol/l up to a peak of 2.0±0.1 mmol/l, p<0.001). The first bout of RMET caused a significant increase of cortisol levels (p<0.01), starting from a basal mean value of 142.9±9.4 ng/ml up to a peak of 188.8±10.3 ng/ml. By contrast, the second bout of RMET did not induce any significant change of cortisol levels (basal: 149.1±9.0 ng/ml, peak: 168.5±5.1 ng/ml). In conclusion, a single bout of RMET is capable of stimulating GH and cortisol secretions and LA production. When a second bout is repeated after 2 h, there is a blunting of GH and cortisol responses with a preservation of LA release. Further studies are needed to schedule long-term RMET protocols capable of persistently stimulating GH-IGF-I release and to maximally enhance the ergogenic and metabolic benefits of this intervention either in normal subjects (e.g. athletes) or patients with an impairment of motor capabilities requested to perform normal daily activities (i.e. severely obese and elderly people).

In recent years, whole body vibration (WBV) has become an efficient complement or alternative to resistance training. Very limited data on the effects of different WBV protocols on anabolic hormones are available. In this study, we compared the growth hormone (GH), blood lactate (LA), and cortisol responses to different protocols involving WBV. Six healthy women recreationally active performed 10 sets of 12 dynamic squats in the following conditions: squatting alone (S), squatting+vibration (SV), squatting+external load (SE), and squatting+external load+vibration (SEV). All responses at the different stimuli determined acute increases in GH, cortisol, and LA. In particular, GH secretion significantly increased in all 4 conditions immediately after the exercise session compared to other time points. Furthermore, a significantly larger increase was identified following SEV as compared to the other conditions. Cortisol concentrations significantly decreased after S, SV and SE whereas they increased significantly following SEV. LA peaks occurred immediately at the end of each condition. However it reached statistical significance only following SEV. The results of our study demonstrate that the combination of squatting+external load+vibration (SEV) could represent the most suitable modality to potentiate the somatotropic function and, indirectly, to obtain an increase in muscle strength and positive changes in the body composition. Further studies are necessary in order to determine the chronic effects of this exercise modality on the hormonal profile.

Background: The abrupt fall in estrogens levels during the menopausal transition may connote an hormonal state predisposing to neurodegenerative disorders, e.g. Alzheimer’s disease (AD). Reportedly, the neurotrophic activity of estrogen involves an interaction with IGF-I. Aim: To evaluate the leukocyte gene expression of progesterone receptor (PR-A/B) and interleukin 6 (IL-6), two parameters under the control of estrogens and involved in the pathogenesis of AD. Subjects: The study was conducted in non-demented women divided into two groups according to their pre- or post-menopausal state; each group being further divided into two subgroups based on their circulating levels of IGF-I (normal or low). An additional sample of AD-affected women served as a comparison group. Results: Estrogens maintained their full activity only when IGF-I levels were in the range of normalcy. On the contrary, if the concentrations of one or both hormones were reduced, estrogens were not anymore capable to control the gene expression of PR-A/B or IL-6. Conclusions: Before administering hormone-based replacement therapy, characterization of the somatotropic function should be performed in the early phase of the menopause.

It is well established that obese patients are hypo-responsive to classical GH-releasing stimuli, including aerobic exercise. Recently, we have demonstrated that whole body vibration was able to markedly stimulate GH secretion in obese patients, thus suggesting that this refractoriness is not absolute but dependent on the GH-releasing stimulus. Furthermore, we have shown the ability of a respiratory muscle endurance training (RMET) to stimulate GH and cortisol secretion in healthy subjects. The objective of this study was to evaluate the effects of RMET on GH and cortisol responses in severely obese patients. Eight severely obese patients (4 M/4 F, mean age±SEM: 22.8±1.6 years, body mass index, BMI: 39.9±1.1 kg/m2) underwent an incremental progressive RMET protocol of 11 daily sessions, obtained through the use of a specifically designed respiratory device (Spiro Tiger®). The 12th session of RMET (15 min duration: 1 min at a respiration rate of 28 acts/min, 5 min at 32 acts/min, 5 min at 34 acts/min, 4 min at 36 acts/min) was associated with blood samplings for determination of GH, cortisol, and lactate (LA) levels. An age- and sex-matched normal-weighted control group (n=7, 4 M/3 F, age: 26.1±3.1 years, BMI: 22.4±0.6 kg/m2) was also recruited. In both normal-weighted subjects and obese patients, GH secretion significantly increased after a 15-min RMET session. Although serum GH levels at 30 min were higher in normal-weighted subjects than in obese patients, there was no statistically significant difference in either GH peaks or net GH areas under the curve between the 2 groups. RMET significantly increased serum cortisol levels in normal-weighted subjects, but was associated to a progressive cortisol decline in obese patients. RMET stimulated LA production, with no significant differences in normal-weighted subjects and in obese patients. A 15-min RMET session was capable to induce a GH response in severely obese patients, which was comparable to that recorded in normal-weighted subjects. A progressive decline in serum cortisol levels occurred in obese patients after RMET, while an opposite pattern (i. e., a significant cortisol increase) was found in normal-weighted subjects. Optimization of long-term RMET protocols could represent a valid strategy to (physiologically) stimulate GH/IGF-I system in those GH hyposecretory states such as obesity.

Myostatin and mechano-growth factor (MGF), an isoform of insulin-like growth factor-I (IGF-I), are two important regulators of muscle hypertrophy. The aim of the present study was to investigate the effects of recombinant human growth hormone (rhGH) and/or testosterone on muscle MGF/IGF-IEa/myostatin expression in intact and hypophysectomized rats treated for 15 d with 1) saline or rhGH, 2) sesame oil or testosterone, 3) saline+sesame oil, or rhGH+testosterone (first experiment) or for 7 d with saline or rhGH (second experiment). Animals were killed by decapitation 24 h or 4 d after the last injection (first or second experiment, respectively). Muscle expressions of MGF, IGF-IEa, and myostatin were determined by RT-PCR. A significant increase in the weight of gastrocnemius muscle was observed only in hypophysectomized rats treated with rhGH alone or in combination with testosterone. Administration of rhGH to hypophysectomized rats caused a marked increase in both MGF and IGF-IEa muscle mRNA levels (without any change in the muscle expression of myostatin), an effect that was abolished when testosterone was combined with rhGH. Conversely, in intact rats rhGH increased myostatin muscle mRNA levels without affecting those of MGF and IGF-IEa. Testosterone, alone or combined with rhGH, induced an inhibition of myostatin expression in the muscle of intact rats, but did not change muscle paradigms of hypophysectomized rats. In conclusion, rhGH and/or testosterone anabolic effects in the muscle are mediated by a different expression of MGF/IGF-IEa/myostatin, which is related to the pituitary function.

Background and objective: Incidence and prevalence of Alzheimer's disease (AD) are higher in postmenopausal women than in age-matched men. Since at menopause the endocrine system and other biological paradigms undergo substantial changes, we thought to be of interest studying whether (and how) the balance between some biological parameters allegedly neuroprotecitve (e.g. related to estrogen, dehydroepiandrosterone and CD36 functions) and others considered pro-neurotoxic (e.g. related to glucocorticoid and interleukin-6 activities) vary during lifespan in either sex in either normalcy or neurodegenerative disorders.Subjects and methods: Along with this aim, we evaluated the gene expression levels of estrogen receptors (ERs), glucocorticoid receptors (HGRs). interleukin-6 (IL-6) and CD36, a scavenger receptor of class B allegedly playing it key role in the proinflammatory events associated with AD in a population of 209 healthy subjects (73M, 106F, 20-91-year old) and 85 AD patients (36M, 49F, 65-89-year old). Results obtained were related to plasma titers of estrogens, cortisol and dehydroepiandrosterone sulfate (DHEAS). Studies were performed in peripheral leukocytes, since these cells (1) are easily obtainable by a simple blood sampling, (2) express many molecules and multiple receptors which are under the same regulatory mechanisms as those operative in the brain and (3) some of them, e.g. monocytes, share many functions with microglial cells.Results: In healthy men all the study parameters were quite stable during lifespan. In women, instead, at menopausal transition, some changes that may predispose to neurodegeneration occurred. In particular, there was (1) an up-regulation of ERs, and a concomitant increase of IL-6 gene expression, events likely due to the loss of the inhibitory control exerted by estradiol (E-2); (2) an increase of HGR alpha:HGR beta ratio, indicative of an augmented cortisol activity on HGR alpha not sufficiently counteracted by the inhibitory HGR beta function; (3) a reduced CD36 expression, directly related to the increased cortisol activity and (4) art auggmented plasma cortisol:DHEAS ratio, widely recognized as an unfavorable prognostic index for the risk of neurodegeneration. In AD patients of both sexes, the expression OF the Study parameters was similar to that found in sex- and age-matched healthy subjects, thus indicating their unrelatedness to the disease, and rather a better correlation with biological events.Conclusions: Menopausal transition is a critical phase of women's life where the occurrence of an unfavorable biological milieu would predispose to an increased risk of neurodegeneration. Collectively, the higher prevalence of AD in the female population would depend, at least in part. oil the presence of favoring biological risk factors, whose contribution to the development of the disease occurs only in the presence of possible age-dependent triggers. Such its beta-amyloid deposition. (C) 2007 Elsevier Inc. All rights reserved.

CD36, a scavenger receptor of class B (SR-B), helps mediate microglial and macrophage response to beta-amyloid fibrils (beta A), and seems to play a key role in the proinflammatory events associated with Alzheimer disease (AD) in many tissues.Peripheral leukocytes express many molecules and multiple receptors which undergo the same regulatory mechanisms as those operative in the brain. Thus, these cells, easily obtainable through peripheral blood sampling, may be used as a tool to investigate changes occurring in inaccessible brain areas.Based on these premises, we investigated the leukocyte expression of CD36 in 70 AD patients and in 30 subjects with mild cognitive impairment (MCI). Results were compared to those of 20 young and 40 age-matched control subjects.Leukocyte expression of CD36 was significantly reduced versus controls in both AD and MCI patients, while in young and old controls there were no age-related changes.Although preliminary, these data indicate that the reduction of CD36 expression in leukocytes is a disease-related phenomenon, occurring since the early stages of AD (MCI). Irrespective of the mechanism(s) underlying such changes, assessment of leukocyte CD36 expression might represent an useful tool to support the diagnosis of AD and to screen MCI patients candidates to develop the disease. (c) 2006 Elsevier Inc. All rights reserved.