Visceral fat sympathectomy ameliorates systemic and local stress response related to chronic sleep restriction.

Disturbance of sleep homeostasis encompasses health issues, including metabolic disorders like obesity, diabetes, and augmented stress vulnerability. Sleep and stress interact bidirectionally to influence the central nervous system and metabolism. Murine models demonstrate that decreased sleep time is associated with an increased systemic stress response, characterized by endocrinal imbalance, including the elevated activity of hypothalamic-pituitary-adrenal axis, augmented insulin, and reduced adiponectin, affecting peripheral organs physiology, mainly the white adipose tissue (WAT). Within peripheral organs, a local stress response can also be activated by promoting the formation of corticosterone. This local amplifying glucocorticoid signaling is favored through the activation of the enzyme 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1). In WAT, 11ß-HSD1 activity is upregulated by the sympathetic nervous system, suggesting a link between sleep loss, augmented stress response, and a potential WAT metabolic disturbance. To gain more understanding about this relationship, metabolic and stress responses of WAT-sympathectomized rats were analyzed to identify the contribution of the autonomic nervous system to stress response-related metabolic disorders during chronic sleep restriction. Male Wistar rats under sleep restriction were allowed just 6 h of daily sleep over eight weeks. Results showed that rats under sleep restriction presented higher serum corticosterone, increased adipose tissue 11ß-HSD1 activity, weight loss, decreased visceral fat, augmented adiponectin, lower leptin levels, glucose tolerance impairment, and mildly decreased daily body temperature. In contrast, sympathectomized rats under sleep restriction exhibited decreased stress response (lower serum corticosterone and 11ß-HSD1 activity). In addition, they maintained weight loss, explained by a reduced visceral fat pad, leptin, and adiponectin, improved glucose management, and persisting decline in body temperature. These results suggest autonomic nervous system is partially responsible for the WAT-exacerbated stress response and its metabolic and physiological disturbances.

Feeding during the resting phase causes gastrointestinal tract dysfunction and desynchronization of metabolic and neuronal rhythms in rats.

BACKGROUND: Disrupted circadian rhythms may result from a misalignment between the environmental cycles (due to shift work, sleep restriction, feeding at an unusual time of day) and endogenous rhythms or by physiological aging. Among the numerous adverse effects, disrupted rhythms affect the brain-gut axis, contributing to the pathogenesis of several diseases in the gastrointestinal tract, for example, abdominal pain, constipation, gastric dyspepsia, inflammatory bowel disease, irritable bowel syndrome, and others. METHODS: This study evaluated the rat gastric emptying, gastrointestinal motility, a clock gene, gut hormones, and the neuron activity on the nucleus of tractus solitarius (NTS), area postrema (AP), and the dorsal motor nucleus of the vagus (DMV) in rats with restricted food access to the rest phase for 4 weeks. KEY RESULTS: Our results show that food restricted to the rest light period disturbed the expression pattern of a series of transcripts, including metabolic and circadian regulation. Also, the secretion of gastrointestinal hormones, gastric emptying, intestinal motility, and NTS, AP, and DMV activity were altered. CONCLUSIONS & INFERENCES: These data indicate the importance of the time of the day food is ingested on the regulation of energy balance and the endocrine activity of the stomach and small intestine, emphasizing the importance of food as a powerful circadian synchronizer and an essential factor for the triggering of gastrointestinal diseases and metabolic problems. These findings offer a novel clue regarding the obesity-promoting effect attributed to feeding time and open the possibility of treating this and other intestinal disorders.

Reversal of pathological motor behavior in a model of Parkinson's disease by striatal dopamine uncaging.

Motor deficits observed in Parkinson's disease (PD) are caused by the loss of dopaminergic neurons and the subsequent dopamine depletion in different brain areas. The most common therapy to treat motor symptoms for patients with this disorder is the systemic intake of L-DOPA that increases dopamine levels in all the brain, making it difficult to discern the main locus of dopaminergic action in the alleviation of motor control. Caged compounds are molecules with the ability to release neuromodulators locally in temporary controlled conditions using light. In the present study, we measured the turning behavior of unilateral dopamine-depleted mice before and after dopamine uncaging. The optical delivery of dopamine in the striatum of lesioned mice produced contralateral turning behavior that resembled, to a lesser extent, the contralateral turning behavior evoked by a systemic injection of apomorphine. Contralateral turning behavior induced by dopamine uncaging was temporarily tied to the transient elevation of dopamine concentration and was reversed when dopamine decreased to pathological levels. Remarkably, contralateral turning behavior was tuned by changing the power and frequency of light stimulation, opening the possibility to modulate dopamine fluctuations using different light stimulation protocols. Moreover, striatal dopamine uncaging recapitulated the motor effects of a low concentration of systemic L-DOPA, but with better temporal control of dopamine levels. Finally, dopamine uncaging reduced the pathological synchronization of striatal neuronal ensembles that characterize unilateral dopamine-depleted mice. We conclude that optical delivery of dopamine in the striatum resembles the motor effects induced by systemic injection of dopaminergic agonists in unilateral dopamine-depleted mice. Future experiments using this approach could help to elucidate the role of dopamine in different brain nuclei in normal and pathological conditions.

Leptin and adiponectin regulate the activity of nuclei involved in sleep-wake cycle in male rats.

Epidemiological and experimental evidence recognize a relationship between sleep-wake cycles and adiposity levels, but the mechanisms that link both are not entirely understood. Adipose tissue secretes adiponectin and leptin hormones, mainly involved as indicators of adiposity levels and recently associated to sleep. To understand how two of the main adipose tissue hormones could influence sleep-wake regulation, we evaluated in male rats, the effect of direct administration of adiponectin or leptin in the ventrolateral preoptic nuclei (VLPO), a major area for sleep promotion. The presence of adiponectin (AdipoR1 and AdipoR2) and leptin receptors in VLPO were confirmed by immunohistochemistry. Adiponectin administration increased wakefulness during the rest phase, reduced delta power, and activated wake-promoting neurons, such as the locus coeruleus (LC), tuberomammillary nucleus (TMN) and hypocretin/orexin neurons (OX) within the lateral hypothalamus (LH) and perifornical area (PeF). Conversely, leptin promoted REM and NREM sleep, including increase of delta power during NREM sleep, and induced c-Fos expression in VLPO and melanin concentrating hormone expressing neurons (MCH). In addition, a reduction in wake-promoting neurons activity was found in the TMN, lateral hypothalamus (LH) and perifornical area (PeF), including in the OX neurons. Moreover, leptin administration reduced tyrosine hydroxylase (TH) immunoreactivity in the LC. Our data suggest that adiponectin and leptin act as hormonal mediators between the status of body energy and the regulation of the sleep-wake cycle.

Temporal dysregulation of hypothalamic integrative and metabolic nuclei in rats fed during the rest phase.

Temporal coordination of organisms according to the daytime allows a better performance of physiological processes. However, modern lifestyle habits, such as food intake during the rest phase, promote internal desynchronization and compromise homeostasis and health. The hypothalamic suprachiasmatic nucleus (SCN) synchronizes body physiology and behavior with the environmental light-dark cycle by transmitting time information to several integrative hypothalamic nuclei, such as the paraventricular nucleus (PVN), dorsomedial hypothalamic nucleus (DMH) and median preoptic area (MnPO). The SCN receives metabolic information mainly via Neuropeptide Y (NPY) inputs from the intergeniculate nucleus of the thalamus (IGL). Nowadays, there is no evidence of the response of the PVN, DMH and MnPO when the animals are subjected to internal desynchronization by restricting food access to the rest phase of the day. To explore this issue, we compared the circadian activity of the SCN, PVN, DMH and MnPO. In addition, we analyzed the daily activity of the satiety centers of the brainstem, the nucleus of the tractus solitarius (NTS) and area postrema (AP), which send metabolic information to the SCN, directly or via the thalamic intergeniculate leaflet (IGL). For that, male Wistar rats were assigned to three meal protocols: fed during the rest phase (Day Fed); fed during the active phase (Night Fed); free access to food (ad libitum). After 21 d, the daily activity patterns of these nuclei were analyzed by c-Fos immunohistochemistry, as well as NPY immunohistochemistry, in the SCN. The results show that eating during the rest period produces a phase advance in the activity of the SCN, changes the daily activity pattern in the MnPO, NTS and AP and flattens the c-Fos rhythm in the PVN and DMH. Altogether, these results validate previous observations of circadian dysregulation that occurs within the central nervous system when meals are consumed during the rest phase, a behavior that is involved in the metabolic alterations described in the literature.

Nicotine smoking concentrations modulate GABAergic synaptic transmission in murine medial prefrontal cortex by activation of α7* and ß2* nicotinic receptors.

Nicotine is the major addictive component of cigarettes, reaching a brain concentration of ~300 nM during smoking of a single cigarette. The prefrontal cortex (PFC) mechanisms underlying temporary changes of working memory during smoking are incompletely understood. Here, we investigated whether 300 nM nicotine modulates γ-aminobutyric acid (GABA) ergic synaptic transmission from pyramidal neurons of the output layer (V) of the murine medial PFC. We used patch clamp in vitro recording from C57BL/6 mice in the whole-cell configuration to investigate the effect of nicotine on pharmacologically isolated GABAergic postsynaptic currents (IPSCs) in the absence or presence of methyllycaconitine (MLA) or dihydro-ß-erythroidine (DHßE), selective antagonists of α7- and ß2-containing (α7* and ß2*) nicotinic acetylcholine receptors (AChRs), respectively. Our results indicated that nicotine, alone or in the presence of MLA, decreases electrically evoked IPSC (eIPSC) amplitude, whereas in the presence of DHßE, nicotine elicited either an eIPSCs amplitude increase or a decrease. In the presence of DHßE, nicotine increased membrane conductance leaving the paired pulse ratio unchanged in all conditions, suggesting a non-ß2* mediated effect. In the presence of MLA, nicotine decreased the mean spontaneous IPSC (sIPSC) frequency but increased their rise time, suggesting a non-α7* AChR-mediated synaptic modulation. Also, in the presence of DHßE, nicotine decreased both eIPSC rise and decay times. No receptors other than α7* and ß2* appear to be involved in the nicotine effect. Our results indicate that nicotine smoking concentrations modulate GABAergic synaptic currents through mixed pre- and post-synaptic mechanisms by activation of α7* and ß2* AChRs.

Differential Recovery Speed of Activity and Metabolic Rhythms in Rats After an Experimental Protocol of Shift-Work.

The circadian system drives the temporal organization of body physiology in relation to the changing daily environment. Shift-work (SW) disrupts this temporal order and is associated with the loss of homeostasis and metabolic syndrome. In a rodent model of SW based on forced activity in the rest phase for 4 weeks, we describe the occurrence of circadian desynchrony, as well as metabolic and liver dysfunction. To provide better evidence for the impact of altered timing of activity, this study explored how long it takes to recover metabolic rhythms and behavior. Rats were submitted to experimental SW for 4 weeks and then were left to recover for one week. Daily locomotor activity, food intake patterns, serum glucose and triglycerides, and the expression levels of hepatic Pparα, Srebp-1c, Pepck, Bmal1 and Per2 were assessed during the recovery period and were compared with expected data according to a control condition. SW triggered the circadian desynchronization of all of the analyzed parameters. A difference in the time required for realignment was observed among parameters. Locomotor activity achieved the expected phase on day 2, whereas the nocturnal feeding pattern was restored on the sixth recovery day. Daily rhythms of plasma glucose and triglycerides and of Pparα, Pepck and Bmal1 expression in the liver resynchronized on the seventh day, whereas Srebp-1c and Per2 persisted arrhythmic for the entire recovery week. SW does not equally affect behavior and metabolic rhythms, leading to internal desynchrony during the recovery phase.

Feeding during the rest phase promotes circadian conflict in nuclei that control energy homeostasis and sleep-wake cycle in rats.

Food intake during the rest phase promotes circadian desynchrony, which has been associated with metabolic diseases. However, the link between circadian rhythm and metabolic alterations is not well understood. To investigate this issue, we explored the circadian rhythm of c-Fos immunoreactivity (IR) in rats fed during the day, during the night or with free access to food for 3 weeks. The analysis was focused on the hypothalamic nuclei, which are interconnected and involved in the control of energy homeostasis and/or arousal: lateral hypothalamus (LH), perifornical area, arcuate, ventrolateral pre-optic (VLPO) and tuberomammillary nuclei. The results show that food intake during the rest phase flattened the circadian c-Fos expression in the LH and perifornical area, and induced a phase shift in the VLPO area. In addition, c-Fos expression was analyzed in the orexin and melanin-concentrating hormone (MCH) neurons of the LH, which are involved in the control of food intake and arousal, and in α-melanin-stimulating hormone and neuropeptide Y (NPY) cells in the arcuate nucleus, all of which are involved in feeding-fasting cycles, energy homeostasis and sending projections to the LH. The results indicate that feeding during the rest phase decreased orexin neuron activation in the light in comparison with the other groups. Feeding during this phase also flattened the activity rhythm of MCH and α-melanin-stimulating hormone neurons and increased NPY IR when the light was turned on. This evidence indicates that mealtime differentially affected the hypothalamic nuclei under investigation leading to a circadian conflict that might account for metabolic impairment.

Locus Ceruleus Norepinephrine Release: A Central Regulator of CNS Spatio-Temporal Activation?

Norepinephrine (NE) is synthesized in the Locus Coeruleus (LC) of the brainstem, from where it is released by axonal varicosities throughout the brain via volume transmission. A wealth of data from clinics and from animal models indicates that this catecholamine coordinates the activity of the central nervous system (CNS) and of the whole organism by modulating cell function in a vast number of brain areas in a coordinated manner. The ubiquity of NE receptors, the daunting number of cerebral areas regulated by the catecholamine, as well as the variety of cellular effects and of their timescales have contributed so far to defeat the attempts to integrate central adrenergic function into a unitary and coherent framework. Since three main families of NE receptors are represented-in order of decreasing affinity for the catecholamine-by: α2 adrenoceptors (α2Rs, high affinity), α1 adrenoceptors (α1Rs, intermediate affinity), and ß adrenoceptors (ßRs, low affinity), on a pharmacological basis, and on the ground of recent studies on cellular and systemic central noradrenergic effects, we propose that an increase in LC tonic activity promotes the emergence of four global states covering the whole spectrum of brain activation: (1) sleep: virtual absence of NE, (2) quiet wake: activation of α2Rs, (3) active wake/physiological stress: activation of α2- and α1-Rs, (4) distress: activation of α2-, α1-, and ß-Rs. We postulate that excess intensity and/or duration of states (3) and (4) may lead to maladaptive plasticity, causing-in turn-a variety of neuropsychiatric illnesses including depression, schizophrenic psychoses, anxiety disorders, and attention deficit. The interplay between tonic and phasic LC activity identified in the LC in relationship with behavioral response is of critical importance in defining the short- and long-term biological mechanisms associated with the basic states postulated for the CNS. While the model has the potential to explain a large number of experimental and clinical findings, a major challenge will be to adapt this hypothesis to integrate the role of other neurotransmitters released during stress in a centralized fashion, like serotonin, acetylcholine, and histamine, as well as those released in a non-centralized fashion, like purines and cytokines.

Activation of the anti-inflammatory reflex blocks lipopolysaccharide-induced decrease in synaptic inhibition in the temporal cortex of the rat.

Stress is a potential trigger for a number of neuropsychiatric conditions, including anxiety syndromes and schizophrenic psychoses. The temporal neocortex is a stress-sensitive area involved in the development of such conditions. We have recently shown that aseptic inflammation and mild electric shock shift the balance between synaptic excitation and synaptic inhibition in favor of the former in this brain area (Garcia-Oscos et al., 2012), as well as in the prefrontal cortex (Garcia-Oscos et al., 2014). Given the potential clinical importance of this phenomenon in the etiology of hyperexcitable neuropsychiatric illness, this study investigates whether inactivation of the peripheral immune system by the "anti-inflammatory reflex" would reduce the central response to aseptic inflammation. For a model of aseptic inflammation, this study used i.p. injections of the bacterial toxin lipopolysaccharide (LPS; 5 µM) and activated the anti-inflammatory reflex either pharmacologically by i.p. injections of the nicotinic α7 receptor agonist PHA543613 or physiologically through electrical stimulation of the left vagal nerve (VNS). Patch-clamp recording was used to monitor synaptic function. Recordings from LPS-injected Sprague Dawley rats show that activation of the anti-inflammatory reflex either pharmacologically or by VNS blocks or greatly reduces the LPS-induced decrease of the synaptic inhibitory-to-excitatory ratio and the saturation level of inhibitory current input-output curves. Given the ample variety of pharmacologically available α7 nicotinic receptor agonists as well as the relative safety of clinical VNS already approved by the FDA for the treatment of epilepsy and depression, our findings suggest a new therapeutic avenue in the treatment of stress-induced hyperexcitable conditions mediated by a decrease in synaptic inhibition in the temporal cortex.

[Alteration of biological rhythms causes metabolic diseases and obesity]. / La alteracion de los ritmos biologicos causa enfermedades metabolicas y obesidad.

The incidence of obesity worldwide has become a serious, constantly growing public health issue that reaches alarming proportions in some countries. To date none of the strategies developed to combat obesity have proved to be decisive, and hence there is an urgent need to address the problem with new approaches. Today, studies in the field of chronobiology have shown that our physiology continually adapts itself to the cyclical changes in the environment, regard-less of whether they are daily or seasonal. This is possible thanks to the existence of a biological clock in our hypothalamus which regulates the expression and/or activity of enzymes and hormones involved in regulating our metabolism, as well as all the homeostatic functions. It has been observed that this clock can be upset as a result of today's modern lifestyle, which involves a drop in physical activity during the day and the abundant ingestion of food during the night, among other factors, which together promote metabolic syndrome and obesity. Hence, the aim of this review is to summarise the recent findings that show the effect that altering the circadian rhythms has on the metabolism and how this can play a part in the development of metabolic diseases.

TITLE: La alteracion de los ritmos biologicos causa enfermedades metabolicas y obesidad.La incidencia de la obesidad a escala mundial se ha convertido en un grave y creciente problema de salud publica, que alcanza en algunos paises proporciones alarmantes, y hasta el momento ninguna de las estrategias desarrolladas para combatir la obesidad se ha demostrado resolutiva, por lo que es urgente abordar el problema con nuevos enfoques. Actualmente, en el estudio de la cronobiologia se ha demostrado que nuestra fisiologia se adapta continuamente a los cambios ciclicos del ambiente, sean estos diarios o estacionales, debido a la presencia de un reloj biologico en nuestro hipotalamo que regula la expresion y actividad de enzimas y hormonas implicadas en la regulacion del metabolismo, asi como de todas las funciones homeostaticas. Se ha observado que este reloj puede alterarse debido al estilo de vida moderno, que implica una baja actividad fisica durante el dia e ingesta abundante de comida durante la noche, entre otros factores, que promueven todos ellos el sindrome metabolico y la obesidad. Por lo tanto, el objetivo de esta revision es resumir los hallazgos recientes que demuestran el efecto de la alteracion circadiana sobre el metabolismo y como esta puede participar en el desarrollo de enfermedades metabolicas.

La alteración de los ritmos biológicos causa enfermedades metabólicas y obesidad / Alteration of biological rhythms causes metabolic diseases and obesity

.La incidencia de la obesidad a escala mundial se ha convertido en un grave y creciente problema de salud pú- blica, que alcanza en algunos países proporciones alarmantes, y hasta el momento ninguna de las estrategias desarrolladas para combatir la obesidad se ha demostrado resolutiva, por lo que es urgente abordar el problema con nuevos enfoques. Actualmente, en el estudio de la cronobiología se ha demostrado que nuestra fisiología se adapta continuamente a los cambios cíclicos del ambiente, sean estos diarios o estacionales, debido a la presencia de un reloj biológico en nuestro hipotálamo que regula la expresión y actividad de enzimas y hormonas implicadas en la regulación del metabolismo, así como de todas las funciones homeostáticas. Se ha observado que este reloj puede alterarse debido al estilo de vida moderno, que implica una baja actividad física durante el día e ingesta abundante de comida durante la noche, entre otros factores, que promueven todos ellos el síndrome metabólico y la obesidad. Por lo tanto, el objetivo de esta revisión es resumir los hallazgos recientes que demuestran el efecto de la alteración circadiana sobre el metabolismo y cómo ésta puede participar en el desarrollo de enfermedades metabólicas (AU)

The incidence of obesity worldwide has become a serious, constantly growing public health issue that reaches alarming proportions in some countries. To date none of the strategies developed to combat obesity have proved to be decisive, and hence there is an urgent need to address the problem with new approaches. Today, studies in the field of chronobiology have shown that our physiology continually adapts itself to the cyclical changes in the environment, regardless of whether they are daily or seasonal. This is possible thanks to the existence of a biological clock in our hypothalamus which regulates the expression and/or activity of enzymes and hormones involved in regulating our metabolism, as well as all the homeostatic functions. It has been observed that this clock can be upset as a result of today’s modern lifestyle, which involves a drop in physical activity during the day and the abundant ingestion of food during the night, among other factors, which together promote metabolic syndrome and obesity. Hence, the aim of this review is to summarise the recent findings that show the effect that altering the circadian rhythms has on the metabolism and how this can play a part in the development of metabolic diseases (AU)

Shift work or food intake during the rest phase promotes metabolic disruption and desynchrony of liver genes in male rats.

In the liver, clock genes are proposed to drive metabolic rhythms. These gene rhythms are driven by the suprachiasmatic nucleus (SCN) mainly by food intake and via autonomic and hormonal pathways. Forced activity during the normal rest phase, induces also food intake, thus neglecting the signals of the SCN, leading to conflicting time signals to target tissues of the SCN. The present study explored in a rodent model of night-work the influence of food during the normal sleep period on the synchrony of gene expression between clock genes and metabolic genes in the liver. Male Wistar rats were exposed to forced activity for 8 h either during the rest phase (day) or during the active phase (night) by using a slow rotating wheel. In this shift work model food intake shifts spontaneously to the forced activity period, therefore the influence of food alone without induced activity was tested in other groups of animals that were fed ad libitum, or fed during their rest or active phase. Rats forced to be active and/or eating during their rest phase, inverted their daily peak of Per1, Bmal1 and Clock and lost the rhythm of Per2 in the liver, moreover NAMPT and metabolic genes such as Pparα lost their rhythm and thus their synchrony with clock genes. We conclude that shift work or food intake in the rest phase leads to desynchronization within the liver, characterized by misaligned temporal patterns of clock genes and metabolic genes. This may be the cause of the development of the metabolic syndrome and obesity in individuals engaged in shift work.

NPY and VGF immunoreactivity increased in the arcuate nucleus, but decreased in the nucleus of the Tractus Solitarius, of type-II diabetic patients.

Ample animal studies demonstrate that neuropeptides NPY and α-MSH expressed in Arcuate Nucleus and Nucleus of the Tractus Solitarius, modulate glucose homeostasis and food intake. In contrast is the absence of data validating these observations for human disease. Here we compare the post mortem immunoreactivity of the metabolic neuropeptides NPY, αMSH and VGF in the infundibular nucleus, and brainstem of 11 type-2 diabetic and 11 non-diabetic individuals. α-MSH, NPY and tyrosine hydroxylase in human brain are localized in the same areas as in rodent brain. The similar distribution of NPY, α-MSH and VGF indicated that these neurons in the human brain may share similar functionality as in the rodent brain. The number of NPY and VGF immuno positive cells was increased in the infundibular nucleus of diabetic subjects in comparison to non-diabetic controls. In contrast, NPY and VGF were down regulated in the Nucleus of the Tractus Solitarius of diabetic patients. These results suggest an activation of NPY producing neurons in the arcuate nucleus, which, according to animal experimental studies, is related to a catabolic state and might be the basis for increased hepatic glucose production in type-2 diabetes.

Disruption of circadian rhythms: a crucial factor in the etiology of depression.

Circadian factors might play a crucial role in the etiology of depression. It has been demonstrated that the disruption of circadian rhythms by lighting conditions and lifestyle predisposes individuals to a wide range of mood disorders, including impulsivity, mania and depression. Also, associated with depression, there is the impairment of circadian rhythmicity of behavioral, endocrine, and metabolic functions. Inspite of this close relationship between both processes, the complex relationship between the biological clock and the incidence of depressive symptoms is far from being understood. The efficiency and the timing of treatments based on chronotherapy (e.g., light treatment, sleep deprivation, and scheduled medication) indicate that the circadian system is an essential target in the therapy of depression. The aim of the present review is to analyze the biological and clinical data that link depression with the disruption of circadian rhythms, emphasizing the contribution of circadian desynchrony. Therefore, we examine the conditions that may lead to circadian disruption of physiology and behavior as described in depressive states, and, according to this approach, we discuss therapeutic strategies aimed at treating the circadian system and depression.

Food intake during the normal activity phase prevents obesity and circadian desynchrony in a rat model of night work.

Shift work or night work is associated with hypertension, metabolic syndrome, cancer, and other diseases. The cause for these pathologies is proposed to be the dissociation between the temporal signals from the biological clock and the sleep/activity schedule of the night worker. We investigated the mechanisms promoting metabolic desynchrony in a model for night work in rats, based on daily 8-h activity schedules during the resting phase. We demonstrate that the major alterations leading to internal desynchrony induced by this working protocol, flattened glucose and locomotor rhythms and the development of abdominal obesity, were caused by food intake during the rest phase. Shifting food intake to the normal activity phase prevented body weight increase and reverted metabolic and rhythmic disturbances of the shift work animals to control ranges. These observations demonstrate that feeding habits may prevent or induce internal desynchrony and obesity.