A. Viggiano

Autonomic Nervous System in the Control of Energy Balance and Body Weight: Personal Contributions

The prevalence of obesity is increasing in the industrialized world, so that the World Health Organization considers obesity as a “pandemia” in rich populations. The autonomic nervous system plays a crucial role in the control of energy balance and body weight. This review summarizes our own data and perspectives, emphasizing the influence exerted by autonomic nervous system on energy expenditure and food intake, which are able to determine the body weight. Activation of the sympathetic discharge causes an increase in energy expenditure and a decrease in food intake, while reduction of food intake and body weight loss determines a reduction of the sympathetic activity. On the other hand, pathophysiological mechanisms of the obesity involve alterations of the sympathetic nervous system in accordance with the “Mona Lisa Hypothesis,” an acronym for “most obesities known are low in sympathetic activity.” Furthermore, the parasympathetic influences on the energy expenditure are analyzed in this review, showing that an increase in parasympathetic activity can induce a paradoxical enhancement of energy consumption.

Injection of orexin A into the diagonal band of Broca induces symphatetic and hyperthermic reactions

This experiment tested the effect of an injection of orexin A into the diagonal band of Broca on the sympathetic activity and body temperature. Concentration of glycerol into white fat of lumbar region, firing rates of sympathetic nerves to interscapular brown adipose tissue (IBAT), IBAT and colonic temperatures, and heart rate were monitored in urethane-anesthetized male Sprague-Dawley rats for 30 min before and 150 min after injections of orexin A (0.4 and 0.7 nmol) into the diagonal band of Broca. The same variables were monitored in control rats with an injection of saline. The results show that orexin A increases glycerol concentration, sympathetic firing rate, IBAT and colonic temperatures, and heart rate. The saline injection did not induce any modification. These findings suggest that the diagonal band of Broca is a cerebral structure involved in the induction of the hyperthermia due to orexin A.

Hyperthermic reactions induced by orexin A: role of the ventromedial hypothalamus

This experiment tested the involvement of the ventromedial hypothalamus (VMH) in the sympathetic and hyperthermic reactions induced by an intracerebroventricular (i.c.v.) injection of orexin A (1.5 nmol). In the first part of the experiment, the firing rate and cytochrome oxidase activity of the VMH neurons, and the colonic temperature were monitored in 12 urethane‐anaesthetized rats before an i.c.v. injection of orexin and over a period of 2 h after the injection. Orexin induced an increase in the firing rate, colonic temperature and cytochrome oxidase activity. A group of 12 rats was used as a control: saline, but not orexin, was injected. No modifications in the firing rate, cytochrome oxidase reactivity and colonic temperature were noted. In the second part of the experiment, 12 rats were anaesthetized and lesioned bilaterally in the VMH with an injection of ibotenic acid. Sham lesions were carried out in 12 control rats. After 48 h, all animals were anaesthetized with ethyl‐urethane. The firing rates of the sympathetic nerves to interscapular brown adipose tissue (IBAT), along with IBAT and colonic temperatures and heart rate were monitored before and over a period of 2 h after an i.c.v. injection of orexin or saline in the lesioned and sham‐lesioned rats. Orexin increased the sympathetic firing rate, IBAT and colonic temperatures and heart rate in the sham‐lesioned rats. These increases were reduced by lesion of VMH. Saline did not induce any modification. These findings indicate that the VMH is involved in the control of the orexin‐induced hyperthermia.

Olanzapine blocks the sympathetic and hyperthermic reactions due to cerebral injection of orexin A.

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 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 olanzapine (10mg/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.

Quetiapine lowers sympathetic and hyperthermic reactions due to cerebral injection of orexin A

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.

Sympathetic and hyperthermic reactions by orexin A: Role of cerebral catecholaminergic neurons

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 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. 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.

Expresso coffee increases parasympathetic activity in young, healthy people

Abstract Caffeine induces modifications of activity of the autonomic nervous system. This study analyzed the effect of a cup of espresso coffee on the heart rate variability (HRV) power spectral analysis, which is a method providing evaluation of the sympathetic and parasympathetic discharge. In young, healthy sedentary subjects (10 male, 10 female; aged 25–30 years), the HRV-power spectrum was evaluated over a period of 150 min after the administration of espresso coffee (caffeine, 75 mg) or decaffeinated coffee (caffeine, < 18 mg) in supine and seated position. Absolute values of the spectrum were summed in low (LF) and high frequencies (HF). The LF and HF spectra were used to estimate the sympathetic and parasympathetic activity, respectively. In the supine position, coffee increases HF, while decaffeinated coffee causes little modifications of HF. In the seated position, HF is not modified by coffee or decaffeinated coffee. Coffee and decaffeinated coffee do not induce any modification of LF in both positions. This experiment indicates that espresso coffee influences parasympathetic activity in the supine position.

Cortical spreading depression induces the expression of iNOS, HIF-1α, and LDH-A

The mechanisms of tolerance to subsequent episodes of ischemia induced by cortical spreading depression (CSD) are not clear. The effects of CSD on the expression of inducible nitric oxide synthase (iNOS), hypoxia inducible factor-1alpha (HIF-1alpha), and lactate dehydrogenase-A (LDH-A) were evaluated in the present experiment. Unilateral CSD was induced in Sprague-Dawley rats by application of KCl on the right cortex and the mRNA levels of iNOS, HIF-1alpha, and LDH-A were evaluated at 15 min, 2 h, 4 h, 6 h or 24 h after CSD. RT-PCR analysis showed: 1) an increase of iNOS mRNA at 15 min, 2 h, 4 h; 2) an increase of HIF-1alpha mRNA at 6 h; 3) an increase of LDH-A mRNA at 4 h. In situ hybridization with specific digoxigenin-labeled oligonucleotides revealed that the mRNA levels were increased at 15 min-2 h for iNOS, 2-4 h for LDH-A and 6 h for HIF-1 after CSD. Immunohistochemistry analysis revealed that levels of iNOS and HIF-1alpha were increased, respectively, at 2 h and 6 h after CSD. These data suggest that CSD promotes the expression of iNOS, HIF-1alpha, and LDH-A in nervous cells giving a neuroprotective effect.

Role of Orexin in Obese Patients in the Intensive Care Unit

Understanding the regulation of appetite and energy expenditure mechanisms is essential for the health and disease. The recognition that the distribution of these regulatory mechanisms plays a central role in the pathogenesis of obesity and associated metabolic syndrome is not new, and it is even more interesting to understand what happens in an obese patient in the Intensive Care Unit (ICU). This review focuses on the catabolic role of orexin, which paradoxically coexists with its anabolic feeding-inducing role. The goal of this review is to provide insight into the biological mechanism governing orexin’s role in energy expenditure, discuss its significance in the context of ICU. Mammals possess a specialized tissue termed Brown Adipose Tissue (BAT) that expends calories to counteract hypothermia. The ability to enhance energy expenditure by manipulating BAT activity is attractive from a therapeutic standpoint, in light of the discovery of metabolically active BAT in adult humans. The finding of a relationship between BAT and orexins levels suggests new research on the possible roles of orexins in many anomalies of energy expenditure, including those of obese patients in the ICU.

Inhibition of long-term potentiation by CuZn superoxide dismutase injection in rat dentate gyrus: Involvement of muscarinic M1 receptor

Long‐term potentiation (LTP) and long‐term depression represent important processes that modulate synaptic transmission that carries out a key role in neural mechanisms of memory. Many studies give strong evidences on a role of the reactive oxygen species in the induction of LTP in CA1 region of hippocampal slices that was inhibited by adding the scavenger enzyme superoxide dismutase (SOD1). Previous data showed that SOD1 is secreted by many cellular lines, including neuroblastoma SK‐N‐BE cells through microvesicles by an ATP‐dependent mechanism; moreover, it has been shown that SOD1 interacts with human neuroblastoma cell membranes increasing intracellular calcium levels via a phospholipase C–protein kinase C pathway activation. The aim of this study was to investigate the effect of intracerebral injection of SOD1 or the inactive form of enzyme (ApoSOD) on the modulation of synaptic transmission in dentate gyrus of the hippocampus in urethane anesthetized rats. The results of the present research showed that intracerebral injection of SOD1 and ApoSOD in the dentate gyrus of the rat hippocampal formation inhibits LTP induced by high‐frequency stimulation of the perforant path. This result cannot be only explained by the dismutation of oxygen radical induced by SOD1 since also ApoSOD, that lacks the enzymatic activity, carries out the same inhibitory effect on LTP induction. J. Cell. Physiol. 227: 3111–3115, 2012.