RESUMO
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.
RESUMO
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.
Assuntos
Ritmo Circadiano , Hipotálamo , Animais , Masculino , Ratos , Ritmo Circadiano/fisiologia , Hipotálamo/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos Wistar , Núcleo Supraquiasmático/metabolismoRESUMO
As obesity and metabolic diseases rise, there is need to investigate physiological and behavioural aspects associated with their development. Circadian rhythms have a profound influence on metabolic processes, as they prepare the body to optimise energy use and storage. Moreover, food-related signals confer temporal order to organs involved in metabolic regulation. Therefore food intake should be synchronised with the suprachiasmatic nucleus (SCN) to elaborate efficient responses to environmental challenges. Human studies suggest that a loss of synchrony between mealtime and the SCN promotes obesity and metabolic disturbances. Animal research using different paradigms has been performed to characterise the effects of timing of food intake on metabolic profiles. Therefore the purpose of the present review is to critically examine the evidence of animal studies, to provide a state of the art on metabolic findings and to assess whether the paradigms used in rodent models give the evidence to support a 'best time' for food intake. First we analyse and compare the current findings of studies where mealtime has been shifted out of phase from the light-dark cycle. Then, we analyse studies restricting meal times to different moments within the active period. So far animal studies correlate well with human studies, demonstrating that restricting food intake to the active phase limits metabolic disturbances produced by high-energy diets and that eating during the inactive/sleep phase leads to a worse metabolic outcome. Based on the latter we discuss the missing elements and possible mechanisms leading to the metabolic consequences, as these are still lacking.
Assuntos
Ritmo Circadiano , Ingestão de Alimentos , Obesidade , Núcleo Supraquiasmático/fisiologia , Animais , Humanos , Atividade MotoraRESUMO
Restricted feeding (RF) during daytime is associated with anticipatory activity before feeding, marked hyperphagia after mealtime, adjustments in hepatic metabolism, and the expression of a food-entrained oscillator (FEO). 24 h rhythmicity of liver PPARα, ß, and γ, peroxisomal markers (PMP70, AOX, and catalase), and free fatty acids (FFAs) during RF was evaluated. The effect of fasting-refeeding was also studied. Results showed (1) higher levels of FFA before feeding, (2) a shift of PPARα and PPARγ before and of PPARß peaks after feeding, (3) an increase in peroxisomal markers, (4) a shift of PMP70 and AOX peaks before feeding, and of maximal catalase activity in the dark period, (5) changes in the fasting-refeeding response, and (6) high correlations (>0.9) of serum corticosterone with PPARα and PPARγ and of PMP70 with PPARß. In conclusion, 24 h rhythmicity of FFA, liver PPARs, and peroxisomal markers are biochemical adaptations associated with daytime RF and FEO expression.