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.

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.