RESUMEN
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.
Asunto(s)
Corticosterona , Enfermedades Metabólicas , Masculino , Ratones , Ratas , Animales , Corticosterona/metabolismo , Leptina/metabolismo , Grasa Intraabdominal/metabolismo , Adiponectina/metabolismo , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/metabolismo , Sistema Hipotálamo-Hipofisario/metabolismo , Ratas Wistar , Sistema Hipófiso-Suprarrenal/metabolismo , Tejido Adiposo/metabolismo , Pérdida de Peso , Sueño , Enfermedades Metabólicas/metabolismo , Simpatectomía , Glucosa/metabolismoRESUMEN
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.
RESUMEN
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.