Microglia is considered the central nervous system (CNS) resident macrophages that establish an innate immune response against pathogens and toxins. However, the recent studies have shown that microglial gene and protein expression follows a circadian pattern; several immune activation markers and clock genes are expressed rhythmically without the need for an immune stimulus. Furthermore, microglia responds to an immune challenge with different magnitudes depending on the time of the day. This review examines the circadian control of microglia function and the possible physiological implications. For example, we discuss that synaptic prune is performed in the cortex at a certain moment of the day. We also consider the implications of daily microglial function for maintaining biological rhythms like general activity, body temperature, and food intake. We conclude that the developmental stage, brain region, and pathological state are not the only factors to consider for the evaluation of microglial functions; instead, emerging evidence indicates that circadian time as an essential aspect for a better understanding of the role of microglia in CNS physiology.

In mammals, time and metabolism are tightly coupled variables; this relationship can be illustrated by numerous examples, such as the circadian variation in food intake or the circadian response to a glucose bolus. We review evidence that the interaction between the suprachiasmatic nucleus and the arcuate nucleus plays a key role in the execution of these functions. The nuclei are reciprocally connected via different projections, and this interaction provides an ideal anatomical framework to modify the temporal output of the hypothalamus to metabolic organs as a consequence of the feedback from the periphery. The suprachiasmatic nucleus–arcuate nucleus relationship is essential to integrate metabolic information into the circadian system and thus adapt circadian rhythms in core body temperature, locomotor activity, food intake, and circulating molecules such as glucose and corticosterone. With the rise in obesity‐associated diseases in the world population, gaining knowledge about this relationship, and the consequences of disturbing this liaison, is essential to understand the pathogenesis of obesity.

What is the central question of this study? What are the factors influencing day-night variations in postprandial triglycerides? What is the main finding and its importance? Rats show low postprandial plasma triglyceride concentrations early in the active period that are attributable to a higher uptake by skeletal muscle and brown adipose tissue. We show that these day-night variations in uptake are driven by the suprachiasmatic nucleus, probably via a Rev-erbα-mediated mechanism and independent of locomotor activity. These findings highlight that the suprachiasmatic nucleus has a major role in day-night variations in plasma triglycerides and that disturbances in our biological clock might be an important risk factor contributing to development of postprandial hyperlipidaemia. Energy metabolism follows a diurnal pattern, mainly driven by the suprachiasmatic nucleus (SCN), and disruption of circadian regulation has been linked to metabolic abnormalities. Indeed, epidemiological evidence shows that night work is a risk factor for cardiovascular disease, and postprandial hyperlipidaemia is an important contributor. Therefore, the aim of this work was to investigate the factors that drive day-night variations in postprandial triglycerides (TGs). Intact and SCN-lesioned male Wistar rats were subjected to an oral fat challenge during the beginning of the rest phase (day) or the beginning of the active phase (night). The plasma TG profile was evaluated and tissue TG uptake assayed. After the fat challenge, intact rats showed lower postprandial plasma TG concentrations early in the night when compared with the day. However, no differences were observed in the rate of intestinal TG secretion between day and night. Instead, there was a higher uptake of TG by skeletal muscle and brown adipose tissue early in the active phase (night) when compared with the rest phase (day), and these variations were abolished in rats bearing bilateral SCN lesions. Rev-erbα gene expression suggests this as a possible mediator of the mechanism linking the SCN and day-night variations in TG uptake. These findings show that the SCN has a major role in day-night variations in plasma TGs by promoting TG uptake into skeletal muscle and brown adipose tissue. Consequently, disturbance of the biological clock might be an important risk factor contributing to the development of hyperlipidaemia.

Metabolic syndrome is a complex, multifactorial disease that affects a growing number of people worldwide. The underlying causes are related to modern lifestyle, including lack of physical activity, consumption of highly caloric western diets, and disruption of the circadian system. Shift workers, who decouple their behavior from the external circadian cycles, have an increased risk for obesity, dyslipidemias, and impaired glucose regulation, all associated with diabetes and metabolic syndrome. In shift workers, at least two factors represent a risk for circadian disruption: exposure to light at night and food intake during the rest phase. [1,2] These two factors can be modeled with rodents in a laboratory setting. [3,4] Rats under constant light display increased adiposity and glucose intolerance after several weeks, [5][6][7] and even an acute light pulse in Eating during the rest phase is associated with metabolic syndrome, proposed to result from a conflict between food consumption and the energy-saving state imposed by the circadian system. However, in nocturnal rodents, eating during the rest phase (day-feeding, DF) also implies food intake during light exposure. To investigate whether light exposure contributes to DF-induced metabolic impairments, animals receive food during the subjective day without light. A skeleton photoperiod (SP) is used to entrain rats to a 12:12 cycle with two short light pulses framing the subjective day. DF-induced adiposity is prevented by SP, suggesting that the conflict between light and feeding stimulates fat accumulation. However, all animals under SP conditions develop glucose intolerance regardless of their feeding schedule. Moreover, animals under SP with ad libitum or night-feeding have increased adiposity. SP animals show a delayed onset of the daily rise in body temperature and energy expenditure and shorter duration of nighttime activity, which may contribute to the metabolic disturbances. These data emphasize that metabolic homeostasis can only be achieved when all daily cycling variables are synchronized. Even small shifts in the alignment of different metabolic rhythms, such as those induced by SP, may predispose individuals to metabolic disease.

Sleep has a major role in learning, memory consolidation, and metabolic function. Although it is known that sleep restriction increases the accumulation of amyloid β peptide (Aβ) and the risk to develop Alzheimer’s disease (AD), the mechanism behind these effects remains unknown. In this review, we discuss how chronic sleep restriction induces metabolic and cognitive impairments that could result in the development of AD in late life. Here, we integrate evidence regarding mechanisms whereby metabolic signaling becomes disturbed after short or chronic sleep restriction in the context of cognitive impairment, particularly in the accumulation of Aβ in the brain. We also discuss the role of the blood-brain barrier in sleep restriction with an emphasis on the transport of metabolic signals into the brain and Aβ clearance. This review presents the unexplored possibility that the alteration of peripheral metabolic signals induced by sleep restriction, especially insulin resistance, is responsible for cognitive deficit and, subsequently, implicated in AD development.