Hypothalamic paraventricular injections of ghrelin: effect on feeding and c-Fos immunoreactivity

Olszewski, Pawel K.; Grace, Martha K.; Billington, Charles J.; Levine, Allen S.

doi:10.1016/s0196-9781(03)00159-1

Cited by 113 publications

(89 citation statements)

References 28 publications

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“…The PBN, DMH, and LH are all critical for the regulation of feeding, body weight, and metabolism. These regions either have ghrelin receptors (40) or express FOS after ghrelin administration (43), and ablation of each of these regions attenuates or abolishes at least some index of FAA (7,9,44,45). The ventromedial nucleus of the hypothalamus is also a good candidate for the effect of ghrelin on FAA.…”

Section: Summary Of Resultsmentioning

confidence: 99%

Stomach ghrelin-secreting cells as food-entrainable circadian clocks

LeSauter

Hoque

Weintraub

et al. 2009

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

281

269

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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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Section: Summary Of Resultsmentioning

confidence: 99%

Stomach ghrelin-secreting cells as food-entrainable circadian clocks

LeSauter

Hoque

Weintraub

et al. 2009

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

281

269

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“…Intra-PVN injection of ghrelin stimulates colonic motor function, an effect that is inhibited by local pretreatment with a NPY1-or CRH-receptor antagonist (54). Activation of the PVN may also contribute to the wake-promoting effects of the intra-LH-injected ghrelin since the LH-infusion of ghrelin activates neurons in the PVN as shown by enhanced c-Fos immunoreactivity (36).…”

Section: Discussionmentioning

confidence: 99%

Ghrelin microinjection into forebrain sites induces wakefulness and feeding in rats

Szentirmai¹,

Kapás²,

Krueger³

2007

American Journal of Physiology-Regulatory, Integrative and Comp

109

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Szentirmai É , Kapás L, Krueger JM. Ghrelin microinjection into forebrain sites induces wakefulness and feeding in rats. Am J Physiol Regul Integr Comp Physiol 292: R575-R585, 2007. First published August 17, 2006; doi:10.1152/ajpregu.00448.2006.-Ghrelin, a gutbrain peptide, is best known for its role in the stimulation of feeding and growth hormone release. In the brain, orexin, neuropeptide Y (NPY), and ghrelin are parts of a food intake regulatory circuit. Orexin and NPY are also implicated in maintaining wakefulness. Previous experiments in our laboratory revealed that intracerebroventricular injections of ghrelin induce wakefulness in rats. To further elucidate the possible role of ghrelin in the regulation of arousal, we studied the effects of microinjections of ghrelin into hypothalamic sites, which are implicated in the regulation of feeding and sleep, such as the lateral hypothalamus (LH), medial preoptic area (MPA), and paraventricular nucleus (PVN) on sleep in rats. Sleep responses, motor activity, and food intake after central administration of 0.04, 0.2, or 1 g (12, 60, or 300 pmol) ghrelin were recorded. Microinjections of ghrelin into the LH had strong wakefulness-promoting effects lasting for 2 h. Wakefulness was also stimulated by ghrelin injection into the MPA and PVN; the effects were confined to the first hour after the injection. Ghrelin's non-rapid-eye-movement sleepsuppressive effect was accompanied by attenuation in the electroencephalographic (EEG) slow-wave activity and changes in the EEG power spectrum. Food consumption was significantly stimulated after microinjections of ghrelin into each hypothalamic site. Together, these results are consistent with the hypothesis that forebrain ghrelinergic mechanisms play a role in the regulation of vigilance, possibly through activating the components of the food intake-and arousalpromoting network formed by orexin and NPY. lateral hypothalamus; medial preoptic area; paraventricular nucleus; electroencephalogram; slow-wave activity; sleep GHRELIN IS A 28-AMINO ACID peptide produced by endocrine cells in the gastrointestinal system and by neurons in the central nervous system (21). Circulating ghrelin is derived mainly from the stomach (1). Plasma ghrelin levels inversely correlate with feeding; fasting increases, while food intake reduces, plasma ghrelin concentrations (7, 61). In the brain, ghrelin is produced by arcuate nucleus (ARC) neurons and by a distinct hypothalamic neuronal population in the internuclear region (6). Ghrelin's actions are mediated by the growth hormone secretagogue receptor (GHS-R) (21). GHS-R mRNA is widely distributed in the gastrointestinal tract, sensory vagus fibers, and the brain. Those hypothalamic nuclei that are implicated in the regulation of feeding and/or sleep-wake activity, such as the lateral hypothalamus (LH), paraventricular nucleus (PVN), ARC, dorsomedial hypothalamic nucleus, anteroventral preoptic nucleus, anterior hypothalamic area, suprachiasmatic nucleus, anterolateral hypothalamic nucleus, and the...

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“…Studies in rodents exploring the precise parenchymal targets for ghrelin's orexigenic effects have identified a number of candidate sites: orexigenic responses have been observed when injected into discrete brain areas that include the hypothalamus (arcuate nucleus, ventromedial nucleus, dorsomedial nucleus, paraventricular nucleus, lateral hypothalamus) (Olszewski et al 2003a;Olszewski et al 2003b;, the nucleus tractus solitarius of the brainstem (Faulconbridge et al 2003), the central nucleus of the amygdala (Olszewski et al 2003) and mesolimbic reward areas (the ventral tegmental area (VTA) and nucleus accumbens (N.Acc) Naleid et al 2005). Activation of hypothalamic and brainstem areas could be of importance for ghrelin's effects on homeostatic feeding that is driven by metabolic need.…”

Section: The Central Ghrelin Signalling Systemmentioning

confidence: 99%

The role of the central ghrelin system in reward from food and chemical drugs

Dickson

Egecioglu

Landgren

et al. 2011

Molecular and Cellular Endocrinology

217

168

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Here we review recent advances that identify a role for the central ghrelin signalling system in reward from both natural rewards (such as food) and artificial rewards (that include alcohol and drugs of abuse). Whereas ghrelin emerged as a stomach-derived hormone involved in energy balance, hunger and meal initiation via hypothalamic circuits, it now seems clear that it also has a role in motivated reward-driven behaviours via activation of the so-called "cholinergic-dopaminergic reward link". This reward link comprises a dopamine projection from the ventral tegmental area (VTA) to the nucleus accumbens together with a cholinergic input, arising primarily from the laterodorsal tegmental area. Ghrelin administration into the VTA or LDTg activates the "cholinergicdopaminergic" reward link, suggesting that ghrelin may increase the incentive value of motivated behaviours such as reward-seeking behaviour ("wanting" or "incentive motivation"). Further, direct injection of ghrelin into the brain ventricles or into the VTA

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Hypothalamic paraventricular injections of ghrelin: effect on feeding and c-Fos immunoreactivity

Cited by 113 publications

References 28 publications

Stomach ghrelin-secreting cells as food-entrainable circadian clocks

Stomach ghrelin-secreting cells as food-entrainable circadian clocks

Ghrelin microinjection into forebrain sites induces wakefulness and feeding in rats

The role of the central ghrelin system in reward from food and chemical drugs

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