Keeping circadian time with hormones

Abstract

Daily variations of metabolism, physiology and behaviour are controlled by a network of coupled circadian clocks, comprising a master clock in the suprachiasmatic nuclei of the hypothalamus and a multitude of secondary clocks in the brain and peripheral organs. Light cues synchronize the master clock that conveys temporal cues to other body clocks via neuronal and hormonal signals. Feeding at unusual times can reset the phase of most peripheral clocks. While the neuroendocrine aspect of circadian regulation has been underappreciated, this review aims at showing that the role of hormonal rhythms as internal time-givers is the rule rather than the exception. Adrenal glucocorticoids, pineal melatonin and adipocyte-derived leptin participate in internal synchronization (coupling) within the multi-oscillatory network. Furthermore, pancreatic insulin is involved in food synchronization of peripheral clocks, while stomach ghrelin provides temporal signals modulating behavioural anticipation of mealtime. Circadian desynchronization induced by shift work or chronic jet lag has harmful effects on metabolic regulation, thus favouring diabetes and obesity. Circadian deregulation of hormonal rhythms may participate in internal desynchronization and associated increase in metabolic risks. Conversely, adequate timing of endocrine therapies can promote phase-adjustment of the master clock (e.g. via melatonin agonists) and peripheral clocks (e.g. via glucocorticoid agonists). Keywords: circadian rhythm, desynchronization, diabetes, feeding time, ghrelin, glucocorticoid, insulin, leptin, melatonin, metabolic disturbances, obesity Date submitted 23 April 2015; date of final acceptance 3 June 2015 IntroductionThe circadian system allows metabolic, physiological and behavioural functions to oscillate (i.e. to alternate periods of activity and rest over 24 h), and by organizing a temporal segregation, it avoids the simultaneous occurrence of conflicting behaviours (e.g. feeding and sleeping) or conflicting cellular functions (e.g. glycogenesis and glycolysis), to name a few. The circadian system also allows these functions to anticipate or be in phase with daily predictable events in the environment, such as the daily alternation of light and dark.The circadian system consists of a network of endogenous clocks, coupled by internal signals via the autonomic nervous system and hormonal rhythms, and synchronized by external cues, including light and food. Ambient light detected by the retina, which itself contains a circadian clock, is the most powerful synchronizer of the master clock located in the suprachiasmatic nuclei of the hypothalamus. By contrast, food ingestion modulates the phase of the peripheral clocks, but usually not the oscillations of the suprachiasmatic clock that remain synchronized to light. This review aims at describing the reciprocal links between the circadian system and hormones involved in metabolism. As will be detailed, circadian clocks control the daily rhythms of circulating hormones. In turn, hormonal cues...

Interplay between the endocrine and circadian systems in fishes

“…Leptin is predominantly expressed in the fish liver, which is an important energy-storing tissue, rather than in adipose tissue as in mammals (Gorissen & Flik 2014, Londraville et al 2014. Given its general role as an anorexigenic hormone, leptin expression is expected to increase after feeding and decrease after fasting, as reported in mammals, where plasma levels of this adipokine oscillate in a diurnal fashion, with increased values after food ingestion (Challet 2015, Kumar et al 2015. In fishes, leptin expression also exhibits an acute and transient postprandial increase in the liver, with hepatic leptin-a expression generally increasing 6 h and 9 h after feeding in teleosts such as common carp (Cyprinus carpio; Huising et al 2006), goldfish , Atlantic salmon (Moen & Finn 2013), orange-spotted grouper (Zhang et al 2013) and Mandarin fish (Siniperca chuatsi; Yuan et al 2016).…”

“…Thus, these species would be expected to experience an increase in blood leptin during the night, as this coincides with low nocturnal activity in goldfish and zebrafish. In mammals, the daily peak in circulating leptin also occurs during the fasting/sleeping period, with levels then declining before waking (reviewed in Patton & Mistlberger 2013, Challet 2015, Kumar et al 2015. All findings to date indicate that leptin facilitates a decreased appetite state during the inactive phase in animals, inhibiting the appearance of FAA.…”

“…The dependence of melatonin, pituitary hormone and glucocorticoid rhythms on the LD cycle has been studied for decades in mammals (Pevet & Challet 2011, Kalsbeek et al 2012, Lin et al 2015 and fishes (Falcón et al 2007(Falcón et al , 2010. However, it is known that many other hormones and neuropeptides (orexin, ghrelin, leptin and insulin) also exhibit daily oscillations (Patton & Mistlberger 2013, Tinoco et al 2014, Challet 2015, Sánchez-Bretaño et al 2015a, Schibler et al 2015. Circadian clocks were once thought to be located only in the central nervous system.…”

“…1. This concept has been well-developed in mammals (Albrecht 2012, Patton & Mistlberger 2013, Challet 2015, Schibler et al 2015, but remains practically unexplored in fishes.…”

“…We first describe the current model of fish circadian system organisation. We then focus on two central messengers (melatonin and orexin) and three hormones (ghrelin, leptin and cortisol) due to their importance in synchronising the circadian system in mammals and/or their recognised roles as nutritional status signals (Pevet & Challet 2011, Albrecht 2012, Patton & Mistlberger 2013, Challet 2015, Schibler et al 2015. We consider these hormones as outputs, reviewing what is known to date about the origin of their rhythmicity and also as putative inputs, whereby they act as temporal endogenous messengers that may entrain endogenous clocks.…”