Non-alcoholic fatty liver disease as a consequence of autonomic imbalance and circadian desynchronization.

The circadian system, headed by the suprachiasmatic nucleus, synchronizes behaviour and metabolism according to the external light-dark cycle through neuroendocrine and autonomic signals. Metabolic diseases, such as steatosis, obesity and glucose intolerance, have been associated with conditions of circadian misalignment wherein the feeding schedule has been moved to the resting phase. Here we describe the physiological processes involved in liver lipid accumulation and show how they follow a circadian pattern importantly regulated by both the autonomic nervous system and the feeding-fasting cycle. We propose that an unbalanced activity of the sympathetic-parasympathetic branches between organs induced by circadian misalignment provides the conditions for the development and progression of non-alcoholic fatty liver disease.

Daily patterns and adaptation of the ghrelin, growth hormone and insulin-like growth factor-1 system under daytime food synchronisation in rats.

Daytime restricted feeding promotes the re-alignment of the food entrained oscillator (FEO). Endocrine cues which secretion is regulated by the transition of fasting and feeding cycles converge in the FEO. The present study aimed to investigate the ghrelin, growth hormone (GH) and insulin-like growth factor (IGF)-1 system because their release depends on rhythmic and nutritional factors, and the output from the system influences feeding and biochemical status. In a daily sampling approach, rats that were fed ad lib. were compared with rats on a reversed (daytime) and restricted feeding schedule by 3 weeks (dRF; food access for 2 h), also assessing the effect of acute fasting and refeeding. We undertook measurements of clock protein BMAL1 and performed somatometry of peripheral organs and determined the concentration of total, acylated and unacylated ghrelin, GH and IGF-1 in both serum and in its main synthesising organs. During dRF, BMAL1 expression was synchronised to mealtime in hypophysis and liver; rats exhibited acute hyperphagia, stomach distension with a slow emptying, a phase shift in liver mass towards the dark period and decrease in mass perigonadal white adipose tissue. Total ghrelin secretion during the 24-h period increased in the dRF group as a result of elevation of the unacylated form. By contrast, GH and IGF-1 serum concentration fell, with a modification of GH daily pattern after mealtime. In the dRF group, ghrelin content in the stomach and pituitary GH content decreased, whereas hepatic IGF-1 remained equal. The daily patterns and synthesis of these hormones had a rheostatic adaptation. The endocrine adaptive response elicited suggests that it may be associated with the regulation of metabolic, behavioural and physiological processes during the paradigm of daytime restricted feeding and associated FEO activity.