Rhythms of ghrelin, leptin, and sleep in rats: effects of the normal diurnal cycle, restricted feeding, and sleep deprivation

Bodosi, Balázs; Gardi, János; Hajdu, I.; Szentirmai, Éva; Obál, F.; Krueger, James M.

doi:10.1152/ajpregu.00294.2004

Cited by 257 publications

(218 citation statements)

References 67 publications

(85 reference statements)

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“…The numerous E-box elements, known targets of circadian clock proteins, present in the promoter region of the ghrelin gene (22) likely play a role in the timing of ghrelin synthesis. Furthermore, plasma levels of ghrelin fluctuate diurnally, with a peak in the day and a trough at night (23), and exogenous ghrelin administration stimulates eating (24).…”

mentioning

confidence: 99%

Stomach ghrelin-secreting cells as food-entrainable circadian clocks

LeSauter

Hoque

Weintraub

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

278

267

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Increases in arousal and activity in anticipation of a meal, termed “food anticipatory activity” (FAA), depend on circadian food-entrainable oscillators (FEOs), whose locations and output signals have long been sought. It is known that ghrelin is secreted in anticipation of a regularly scheduled mealtime. We show here that ghrelin administration increases locomotor activity in nondeprived animals in the absence of food. In mice lacking ghrelin receptors, FAA is significantly reduced. Impressively, the cumulative rise of activity before food presentation closely approximates a Gaussian function ( r = 0.99) for both wild-type and ghrelin receptor knockout animals, with the latter having a smaller amplitude. For both groups, once an animal begins its daily anticipatory bout, it keeps running until the usual time of food availability, indicating that ghrelin affects response threshold. Oxyntic cells coexpress ghrelin and the circadian clock proteins PER1 and PER2. The expression of PER1, PER2, and ghrelin is rhythmic in light–dark cycles and in constant darkness with ad libitum food and after 48 h of food deprivation. In behaviorally arrhythmic-clock mutant mice, unlike control animals, there is no evidence of a premeal decrease in oxyntic cell ghrelin. Rhythmic ghrelin and PER expression are synchronized to prior feeding, and not to photic schedules. We conclude that oxyntic gland cells of the stomach contain FEOs, which produce a timed ghrelin output signal that acts widely at both brain and peripheral sites. It is likely that other FEOs also produce humoral signals that modulate FAA.

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mentioning

confidence: 99%

Stomach ghrelin-secreting cells as food-entrainable circadian clocks

LeSauter

Hoque

Weintraub

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

278

267

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“…Ghrelin stimulates GH secretion and promotes wakefulness, weight gain, and adrenocorticotropic hormone and cortisol release in humans and rodents (Frieboes et al, 1995;Wren et al, 2000;Diano et al, 2006;Szentirmai et al, 2007). Peripheral ghrelin levels rise sharply before main meals and decrease once the animal has been fed, most strikingly under restricted feeding conditions (Sugino et al, 2002;Kalra et al, 2003;Bodosi et al, 2004). Under fasting conditions, plasma ghrelin peaks match the previous pattern of daily meals in humans (Natalucci et al, 2005).…”

Section: Introductionmentioning

confidence: 89%

“…Contrary to the well documented effects of ghrelin on appetite, GH release (van der Lely et al, 2004) and the sleep-wake cycle (Weikel et al, 2003;Bodosi et al, 2004), little is known about the effects of ghrelin on circadian rhythms. As a peripheral and central hormone directly implicated in appetite and feeding-related activity, ghrelin is a good candidate signal for food entrainment.…”

Section: Introductionmentioning

confidence: 95%

Ghrelin Effects on the Circadian System of Mice

Yannielli

Molyneux²,

Harrington³

et al. 2007

J. Neurosci.

118

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The orexigenic peptide ghrelin stimulates both food intake and growth hormone release and is synthesized in the stomach and in hypothalamic areas involved in feeding control. The suprachiasmatic nuclei of the hypothalamus (SCN) control most circadian rhythms, although there is evidence that some oscillators, such as food-entrainable oscillators, can drive activity rhythms even after SCN ablation. Ghrelin levels exhibit a circadian rhythm and closely follow feeding schedules, making this peptide a putative candidate for food-related entraining signals. We examined the response of the SCN to ghrelin treatments in vitro, by means of electrophysiological and bioluminescence recordings, and in vivo, by assessing effects on the phase of locomotor activity rhythms. Ghrelin applied at circadian time 6 in vitro to cultured SCN slices induced an ϳ3 h phase advance. In addition, ghrelin phase advanced the rhythm of PER2::LUC (Period2::Luciferase) expression in cultured SCN explants from mPer2Luc transgenic mice. In vivo, intraperitoneal administration of ghrelin or a synthetic analog, growth hormone-releasing protein-6 (GHRP-6), to ad libitum fed animals failed to alter circadian phase. When injected after 30 h of food deprivation, GHRP-6 induced a phase advance compared with saline-injected animals. These results indicate that ghrelin may play a role in the circadian system by exerting a direct action on the SCN and that the system as a whole may become sensitive to ghrelin and other feeding-related neuropeptides under conditions of food restriction.

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“…A shift in meal timing led to a shift in the plasma leptin peak in both humans and rodents. 23,24 Moreover, leptin levels are reduced during starvation and malnutrition. 25 Leptin expression in adipocytes is induced by insulin, melanyl-CoA, adenosine triphosphate, glucosamine and short-chain fatty acids, but it is inhibited by cyclic adenosine 5'-monophosphate and long-chain fatty acid.…”

Section: Introductionmentioning

confidence: 99%

Leptin in immuno-rheumatological diseases

et al. 2011

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Leptin is one of the most important hormones secreted by adipocytes, with a variety of physiological roles related to the control of metabolism and energy homeostasis. Since its discovery in 1994, leptin has attracted increasing interest in the scientific community for its pleiotropic actions. One of these functions is the relationship between nutritional status and immune competence. It structurally resembles proinflammatory cytokines, such as IL-6 and IL-12. The cytokine-like structural characteristic of leptin is implicative of its function in regulating immune responses. The role of leptin in regulating immune responses has been assessed in vitro as well as in clinical studies. It has been shown that disease conditions of reduced leptin production are associated with increased infection susceptibility. Conversely, immune-mediated disorders, such as autoimmune diseases, are associated with the increased secretion of leptin and the production of proinflammatory pathogenic cytokines. In this paper, we review the most recent advances of the role of leptin in immune-rheumatological diseases, and we discuss whether strategies aimed at modifying leptin levels could represent innovative and therapeutic tools for autoimmune disorders. Keywords: adipokines; autoimmune diseases; leptin; rheumatic diseases INTRODUCTIONThe existence of a factor secreted by white adipose tissue (WAT), which acts to control feeding, weight and WAT mass, was first proposed by Kennedy 1 and is supported by monogenic mutations resulting in obesity. [2][3][4] WAT is composed of adipocytes filled mainly with triacylglycerol and embedded in loose connective tissue containing adipocyte precursors, fibroblasts, immune and other cells. Obesity, the condition that originally motivated the research on WAT, is characterized by low-grade systemic inflammation. It is thought that excess WAT can contribute to the maintenance of obesity through inflammation-inducing lipotoxicity by secreting factors that stimulate the synthesis of inflammatory agents in other organs and by secreting inflammatory agents itself. 5 The current view of WAT states that it is an active contributor to body homeostasis by sending out and responding to signals that modulate appetite, energy expenditure, insulin sensitivity, the endocrine and reproductive systems, bone metabolism, inflammation and immunity. 6 Several findings have converged to indicate that adipocytes share certain properties with immune cells, such as complement activation 7 and proinflammatory cytokine production. 8 Fat cell precursors also share features with macrophages. Numerous genes that code for transcription factors, cytokines, inflammatory signaling molecules, and fatty acid transporters are essential for adipocyte biology and are also expressed and functional in macrophages. 9 Adipose tissue secrets a variety of factors: the term 'adipokine' is generally given to any protein that can be synthesized and secreted by adipocytes. Among these factors, only leptin and adiponectin (and possibly resistin, adipsi...

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Rhythms of ghrelin, leptin, and sleep in rats: effects of the normal diurnal cycle, restricted feeding, and sleep deprivation

Cited by 257 publications

References 67 publications

Stomach ghrelin-secreting cells as food-entrainable circadian clocks

Stomach ghrelin-secreting cells as food-entrainable circadian clocks

Ghrelin Effects on the Circadian System of Mice

Leptin in immuno-rheumatological diseases

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