Massimo Morè

Feeding Behavior in Mammals Including Humans

The complex control of food intake and energy metabolism in mammals relies on the ability of the brain to integrate multiple signals indicating the nutritional state and the energy level of the organism and to produce appropriate responses in terms of food intake, energy expenditure, and metabolic activity. Central regulation of feeding is organized as a long‐loop mechanism involving humoral signals and afferent neuronal pathways to the brain, processing in hypothalamic neuronal circuits, and descending commands using vagal and spinal neurons. Sensor mechanisms or receptors sensitive to glucose and fatty acid metabolism, neuropeptide and cannabinoid receptors, as well as neurotransmitters and neuromodulators synthesized and secreted within the brain itself are all signals integrated in the hypothalamus, which therefore functions as an integrator of signals from central and peripheral structures. Homeostatic feedback mechanisms involving afferent neuroendocrine inputs from peripheral organs, like adipose tissue, gut, stomach, endocrine pancreas, adrenal, muscle, and liver, to hypothalamic sites thus contribute to the maintenance of normal feeding behavior and energy balance. In addition to transcriptional events, peripheral hormones may also alter firing and/or connection (synaptology) of hypothalamic neuronal networks in order to modulate food intake. Moreover, intracellular energy sensing and subsequent biochemical adaptations, including an increase in AMP‐activated protein kinase activity, occur in hypothalamic neurons. Understanding the regulation of appetite is clearly a major research effort but also seems promising for the development of novel therapeutic strategies for obesity.

Low-intermediate dose testosterone replacement therapy by different pharmaceutical preparations improves frailty score in elderly hypogonadal hyperglycaemic patients

Abstract An open-label follow-up study of low-to-intermediate dose testosterone replacement therapy (TRT) was conducted in 64 overweight patients (aged 65–75 years) with late onset hypogonadism (LOH) and increased fasting plasma glucose (FPG). Patients were subdivided into four treatment groups: oral testosterone (T) (T undecanoate, 80 mg/d), transmucosal T (60 mg/d), transdermal T (30 mg/d) or no treatment (control), and evaluated at 0 and 6 months. FPG, hemoglobin (Hb), prostate-specific antigen (PSA) and total T were measured and the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) index was calculated. Body mass index (BMI), waist circumference, fitness level (6-min walking test), Aging Males’ Symptoms (AMS) scale, handgrip strength and energy expenditure with physical activity (Minnesota questionnaire for Leisure Time Physical Activity (LTPA)) were evaluated and a “frailty score” (based on: grip strength, gait speed and LTPA) was calculated. T levels increased in all treatment groups; the oral T group had values still in the hypogonadal range (5.9 ± 1.1 nmol/L). PSA and Hb concentrations did not change in any group. BMI, waist circumference, FPG and HOMA-IR improved in all T-treated groups after 6 months, with a greater effect seen with transmucosal and transdermal T compared with oral T. This study indicates that low-to-intermediate dose TRT may be safely utilized in LOH patients to ameliorate somatic and psychological frailty symptoms in association with improved anthropometric and glycometabolic parameters in aging, overweight men with LOH and impaired fasting glucose.

Metabolic Syndrome, Adipokines and Hormonal Factors in Pharmacologically Untreated Adult Elderly Subjects from the Brisighella Heart Study Historical Cohort

Objective: Our aim was to evaluate the relation of the sex hormone pattern and the serum level of the main adipokines with metabolic syndrome (MS) and its components in a cohort of pharmacologically untreated adult elderly subjects. Methods: From the historical cohort of the Brisighella Heart Study we selected 199 adult healthy subjects aged 62.5 ± 12.4 years. Men and women included in the age class subgroups were matched for BMI, waist circumference, blood pressure, heart rate, fasting plasma glucose, and plasma lipids. In these subjects we measured leptin, adiponectin, ghrelin, testosterone, estrone, and deydroepiandrosterone sulphate. Results: Men without MS had significantly lower leptin/adiponectin ratio than men with MS. Women without MS had a lower leptin level and leptin/adiponectin ratio than women with MS, but had significantly higher adiponectin, estrone, and deydroepiandrosterone levels. In men, the leptin/adiponectin ratio is the main factor associated with MS diagnosis (OR 3.36, 95% CI 1.40–8.08), while in women adiponectin alone appears to be a protective factor (OR 0.87, 95% CI 0.79–0.95). Conclusion: In a sample of pharmacologically untreated adult elderly subjects, leptin/adiponectin ratio seems to be the factor that is more strongly associated with MS (especially in men) and its components, though this is true to a different degree in men and women.

Adipokines and Sexual Hormones Associated with the Components of the Metabolic Syndrome in Pharmacologically Untreated Subjects: Data from the Brisighella Heart Study

We evaluated the association of the sex hormone pattern and the serum level of the main adipokines to metabolic syndrome (MS) and its components in 199 pharmacologically untreated subjects. Men and women included in the age-class subgroups were matched for body mass index, waist circumference, blood pressure, heart rate, fasting plasma glucose, and plasma lipids. Men without MS had significantly lower leptin/adiponectin ratio than men with MS. Women without MS had lower leptin and leptin/adiponectin ratio than women with MS but had significantly higher adiponectin, estrone, and dehydroepiandrosterone levels. In men, the leptin/adiponectin ratio is the main factor associated to MS diagnosis (OR: 3.36, 95% CI 1.40–8.08), while in women adiponectin alone appears to be a protective factor (OR: 0.87, 95% CI 0.79–0.95). In conclusion, in a sample of pharmacologically untreated subjects, leptin/adiponectin ratio seems to be the factor more strongly associated to MS and its components.

Free Triiodothyronine and Cholesterol Levels in Euthyroid Elderly T2DM Patients.

Thyroid function regulates lipid metabolism. Despite the fact that T2DM is more prevalent in the elderly, often associates with thyroid dysfunction and increases cardiovascular risk both per se and via high TC and LDL-C levels, the association of the latter with FT3 and FT4 levels has not yet been fully investigated in T2DM. While trying to fill this gap in 296 elderly outpatients with T2DM, we found that TC and LDL-C correlated negatively with FT4 and positively with FT3. When divided according to treatment by oral hypoglycaemic agents (OHA) and insulin (IT), they reacted differently with respect to investigated associations: in the OHAs TC and LDL-C correlated negatively with FT4 and showed no association with FT3, whereas, in the ITs TC and LDL-C correlated positively with FT3 and negatively with FT4. When controlled for possible confounding factors, these associations did not change in the ITs but were missing in the OHAs. Recent literature reports upon complex hypothalamic and peripheral interactions between T2DM and thyroid, and suggests T3 to enhance cholesterol synthesis and to have a role in insulin resistance states. Further investigations are needed to understand the intimate mechanisms of lipid metabolism in T2DM with respect to thyroid function.

Thyrotropin-releasing hormone enhances event-related brain potentials and growth hormone release in man

Changes in contingent negative variation (CNV), a brain-evoked potential related in arousal, as well as in serum triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), prolactin (PRL), cortisol and growth hormone (GH) levels were recorded in 12 male volunteers receiving either thyrotropin-releasing hormone (TRH) or saline infusion. Only during TRH administration an increase in CNV (P less than 0.02) and, 30 min later, in GH (P less than 0.05) occurred; thyroid hormones and PRL increased as well, in the absence of any correlation with CNV areas. Cortisol was not affected by TRH. As dopamine (DA) agonistic drugs notoriously increase both CNV areas and GH levels and experimental evidence for prodopaminergic properties of TRH has accumulated in animal models, a possible explanation of the results here presented might be the activation of DA pathways by TRH also in the human.

A short term −12° head down tilt does not mimic microgravity in terms of human gonadal function

A significant reversible decrease in testosterone (T) has been associated with microgravity in male rodents and humans. Urinary T excretion increases in primates under hypergravity. Hypogonadism is somehow related to abnormally high levels of leptin (L), a hormone produced by the adipose tissue which has been found to increase under microgravity simulation conditions like head down bed rest (HDBR). The aim of this study was to assess hemodynamic and pituitary-adrenal and -gonadal adaptation to an acute HDBR test to be eventually used on a routine basis to get better prepared to next space flights. The Authors performed a 1 hour −12° HDBR in 6 male and 6 female volunteers who underwent heart rate and blood pressure measurement together with a blood draw three times at 30 min intervals from the start to the end of the test for L, T, estradiol (E2), LH, androstenedione (A), cortisol (F), ACTH. 12 age- and sexmatched control subjects followed the same protocol except for keeping the sitting position all the time. According to the ANOVA for repeated measures, no changes occurred in L, T, E2 or LH whereas A, F and ACTH significantly decreased independently of gender. During HDBR systolic blood pressure decreased in both genders, diastolic blood pressure decreased significantly only in men and HR showed a more clear-cut decrease in women than in men. As a conclusion, such an acute steep-slope HDBR protocol may be efficiently used to testing immediate individual haemodynamic or adrenal response to microgravity but is not suitable for studies concerning gonadal adaptation.