Metabolic signals in sleep regulation: recent insights

Figures & data

Figure 1 Bidirectional relationship between circadian clock, sleep-wake, and fasting-feeding behavior underlies maintenance of energy balance in the body.

Figure 2 The neuronal connections between circadian, sleep, and feeding centers within the hypothalamus.

Notes: The efferent projections from suprachiasmatic nucleus (SCN) target the dorsal subparaventricular zone (dSPZ) and ventral subparaventricular zone (vSPZ) with a subset of the axons extending to the dorsomedial nucleus (DMH) in the hypothalamus. Few direct axonal inputs from SCN and ventral SPZ to the sleep-regulating area of ventrolateral preoptic area (VLPO), and a larger contingent of the axons project to the dorsomedial hypothalamus (DMH). The DMH also receives inputs from the arcuate nucleus, which is recognized for regulating food intake and energy expenditure (EE) and sends projections to ventromedial hypothalamus (VMH). The DMH sends divergent afferents to i) sleep regulation center VLPO, ii) paraventricular nucleus (PVN) containing the neurons synthesizing corticotropin-releasing hormone and neurons that mediate preganglionic output to autonomous nervous system, and iii) lateral hypothalamus (LH), an area that contains the hunger-stimulating and wakefulness-promoting peptides.

Figure 3 The interaction between peripheral and central signals regulating circadian, sleep, and feeding centers within hypothalamus.

Notes: The peripheral signals first act on the first-order neurons of the arcuate nucleus to release orexinergic or anorexinergic peptides, which in turn act on the second-order neurons to regulate both sleep and feeding behavior. Finally, changes in the levels of these signals induced by sleep and feeding regulate the peripheral system.
Abbreviations: AgRP, agouti-related protein; BDNF, brain-derived neurotrophic factor; CART, cocaine- and amphetamine-regulated transcript; CRH, corticotropin-releasing hormone; DMH, dorsomedial nucleus; LH, lateral hypothalamus; MCH, melanin-concentrating hormone; NPY, neuropeptide Y; POMC, proopiomelanocortin; PVN, paraventricular/nucleus; VMH, ventromedial hypothalamus; GLP1, glucagon like peptide 1; CCK, Cholecystokinin.

Table 1 Central and peripheral signals involved in energy balance and sleep regulation

Hormone/neuropeptide	Site of synthesis	Function		References
		Energy metabolism	Sleep
Leptin	Adipose, GI	Decreases appetite, increases energy expenditure	During sleep deprivation, decrease in leptin	^Citation64,Citation75
Ghrelin	GI	Orexigenic, decreases energy expenditure	During sleep deprivation, increase in ghrelin	^Citation63,Citation137
			Induces wakefulness
Obestatin	GI	Decreases appetite	Sleep-promoting effect triggers	^Citation138,Citation139
			NREM sleep and reduces SWA
Cholecystokinin	GI	Decreases appetite, energy expenditure	Induces postprandial sleep	^Citation140,Citation141
Glucagon like peptide 1	GI	Decreases appetite	Delayed satiety response after sleep deprivation	^Citation142,Citation143
Peptide YY	GI	Decreases appetite	Elevated with sleep deprivation	^Citation8,Citation144
Neuromedin	GI, brain	Decreases appetite, increases energy expenditure	Sleep-wake architecture, NREM–REM transitions	^Citation145
Neuropeptide Y	Hypothalamus	Anorexigenic	Sleep onset, modulates REM, sleep architecture	^Citation146^–^Citation149
Agouti-related peptide	Hypothalamus	Anorexigenic	Sleep-wake regulation	^Citation149,Citation150
Proopiomelanocortin	Hypothalamus	Suppresses food intake	Sleep-wake regulation	^Citation149,Citation151,Citation152
Orexin	Hypothalamus	Appetite stimulating	Increases wakefulness, suppresses REM	^Citation47,Citation153,Citation154
Thyrotropin-releasing hormone	Hypothalamus	Anorexigenic	Arousal	^Citation149,Citation155
Urocortin	Hypothalamus	Anorexigenic, feeding and EE during stress	Sleep-wake pattern (wake, NREM)	^Citation156,Citation157
Brain-derived neurotrophic factor	Hypothalamus	Anorexigenic, hedonic food intake	Sleep onset	^Citation30,Citation31
Melanin-concentrating hormone	Hypothalamus	Orexigenic-appetite stimulating	Sleep-promoting effect	^Citation158
Corticotropin-releasing hormone	Hypothalamus	Anorexigenic, feeding and energy expenditure during stress	REM sleep, rebound sleep following sleep deprivation	^Citation157,Citation159,Citation160
Glucocorticoids	Adrenal cortex	Feeding	Elevated with sleep deprivation and wakefulness	^Citation161,Citation162

Abbreviations: GI, gastrointestinal; NREM, non-rapid eye movement; REM, rapid eye movement; EE, energy expenditure; SWA, slow wave activity.

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