Brain neuropeptide Y: An integrator of endocrine, metabolic and behavioral processes

Leibowitz, Sarah F.

doi:10.1016/0361-9230(91)90121-y

Cited by 148 publications

(58 citation statements)

References 44 publications

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“…ARC neurons not only synthesize and release neuropeptide Y, involved in feeding (Leibowitz, 1991;Stanley, 1993) and endocrine (McDonald and Koenig, 1993) regulation, but also express receptors for leptin (Hakansson et al, 1998), the signal that adipose tissue releases into the vascular system that reduces food intake and plays a key role in some forms of obesity (Zhang et al, 1994); falling leptin levels may initiate mechanisms for energy conservation (Flier and Maratos-Flier, 1998). Our finding that hypocretin regulates the synaptic input to these arcuate cells and that hypocretincontaining axons strongly innervate this area suggests the hypocretin is in a key position to influence neurons that are the hub for vascular signals from the periphery and afferent and efferent axonal signals involved in feeding.…”

Section: Hypocretin and Energy Homeostasismentioning

confidence: 99%

Presynaptic and Postsynaptic Actions and Modulation of Neuroendocrine Neurons by a New Hypothalamic Peptide, Hypocretin/Orexin

et al. 1998

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A new orexigenic peptide called hypocretin (orexin) has recently been described in neurons of the lateral hypothalamus and perifornical area. The medial and lateral hypothalamus have been loosely called satiety and feeding centers of the brain, respectively. Approximately one-third of all medial and lateral hypothalamic neurons tested, but not hippocampal neurons, show a striking nanomolar sensitivity to hypocretin. As studied with calcium digital imaging with fura-2, hypocretin raises cytoplasmic calcium via a mechanism based on G-protein enhancement of calcium influx through plasma membrane channels. The peptide has a potent effect at both presynaptic and postsynaptic receptors. Most synaptic activity in hypothalamic circuits is attributable to axonal release of GABA or glutamate. With whole-cell patch-clamp recording, we show that hypocretin, acting directly at axon terminals, can increase the release of each of these amino acid transmitters. Two hypocretin peptides, hypocretin-1 and hypocretin-2, are coded by a single gene; neurons that respond to one peptide also respond to the other. In addition to its effect on feeding, we find that this peptide also regulates the synaptic activity of physiologically identified neuroendocrine neurons studied in hypothalamic slices containing the arcuate nucleus, suggesting a second function of hypocretin in hormone regulation. The widespread distribution of hypocretin axons, coupled with the strong response to the peptide at both presynaptic and postsynaptic sites, suggests that the peptide probably modulates a variety of hypothalamic regulatory systems and could regulate the axonal input to these regions presynaptically.

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Section: Hypocretin and Energy Homeostasismentioning

confidence: 99%

Presynaptic and Postsynaptic Actions and Modulation of Neuroendocrine Neurons by a New Hypothalamic Peptide, Hypocretin/Orexin

et al. 1998

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“…Over the past decade, investigators have accumulated extensive evidence to suggest an important role for specific putative neurotransmitters in energy and nutrient homeostasis (22,189,199). Two neurochemicals that have received considerable attention are the peptide NPY and the catecholamine NE.…”

Section: Interactions Between Cort Insulin and Hypothalamic Neurochementioning

confidence: 99%

“…This steroid-peptide system, similar to the CORT-NPY system, responds to a depletion in nutrient stores. That is, prior salt depletion enhances the sensitivity of the ALDO-ANG system (20), while carbohydrate deprivation increases the activity of the CORT-NPY system (199,234,235).…”

Section: Additional Steroid-peptide Systems Involved In Nutrient Ingementioning

confidence: 99%

Adrenal Steroid Receptors: Interactions with Brain Neuropeptide Systems in Relation to Nutrient Intake and Metabolism

Tempel

Leibowitz

1994

J Neuroendocrinology

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195

127

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The glucocorticoid, corticosterone (CORT), is believed to have an important function in modulating nutrient ingestion and metabolism. Recent evidence described in this review suggests that the effects of this adrenal hormone are mediated through two steroid receptor subtypes, the type I mineralocorticoid receptor and the type II glucocorticoid receptor. These receptors, which have different affinities for CORT, respond to different levels of circulating hormone. They mediate distinct effects of the steroid, which can be distinguished by the specific nutrient ingested and by the particular period of the circadian cycle.Under normal physiological conditions, the type I receptor is tonically activated, either by low basal levels of circulating CORT (0.5-2 pg%) normally available across the circadian cycle or possibly by the mineralocorticoid aldosterone. This type I activation is required for the maintenance of fat ingestion and fat deposition that occurs during most meals of the feeding cycle. In contrast, the type II receptor is phasically activated by moderate levels of CORT (2-1 0 pg%) normally reached during the circadian peak. Activation of this receptor is required for the natural surge in carbohydrate ingestion and metabolism that is essential at the onset of the active feeding cycle when the body's glycogen stores are at their nadir, and gluconeogenesis is needed to maintain blood glucose levels. This receptor is also activated during periods of increased energy requirements, such as, after exercise and food restriction, when CORT levels rise further ( > 10 pg%) and when its catabolic effects on fat and protein stores predominate to provide additional substrates for glucose homeostasis. These functions of CORT on fat and carbohydrate balance are mediated, in part, by type I and type II receptors located within the hypothalamic paraventricular nucleus, which is known to have key functions in controlling nutrient intake and metabolism, as well as circulating CORT levels. Moreover, the type II receptors within this nucleus, in addition to the arcuate nucleus, may interact positively with the peptide, neuropeptide Y, and the catecholamine, norepinephrine, both of which act to enhance natural carbohydrate feeding and CORT release at the onset of the natural feeding cycle.Thus, under normal conditions, endogenous CORT has a primary function in controlling nutrient ingestion and metabolism over the natural circadian cycle, through the coordinated action of the type I and type II steroid receptor systems. Through this action, CORT has impact on total caloric intake and body weight gain over the long term. Moreover, under conditions of obesity, diabetes and food restriction, steroid receptor function is greatly disturbed in association with chronic high circulating levels of CORT and abnormal glucose homeostasis. These disturbances in steroid action, along with dysfunction in brain neurochemical processes, very possibly contribute to the maintenance of hyperphagia and body weight gain in obese and diabetic ...

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“…This conjugate (NPY-SAP) targets NPY receptor-expressing neurons for destruction by binding to internalizing NPY receptors. Our injections were directed at the Arc, where targeted neurons include (among others) pro-opiomelanocortin neurons and NPY and Agouti gene-related peptide (AGRP) coexpressing neurons, which are involved in both feeding and sleep (25,31,34). We found that NPY receptor-expressing neurons in the MBH are required for integration of sleep-wake and feeding rhythms.…”

mentioning

confidence: 99%

Circadian integration of sleep-wake and feeding requires NPY receptor-expressing neurons in the mediobasal hypothalamus

Wiater

Mukherjee

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

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Sleep and feeding rhythms are highly coordinated across the circadian cycle, but the brain sites responsible for this coordination are unknown. We examined the role of neuropeptide Y (NPY) receptor-expressing neurons in the mediobasal hypothalamus (MBH) in this process by injecting the targeted toxin, NPY-saporin (NPY-SAP), into the arcuate nucleus (Arc). NPY-SAP-lesioned rats were initially hyperphagic, became obese, exhibited sustained disruption of circadian feeding patterns, and had abnormal circadian distribution of sleep-wake patterns. Total amounts of rapid eye movement sleep (REMS) and non-REMS (NREMS) were not altered by NPY-SAP lesions, but a peak amount of REMS was permanently displaced to the dark period, and circadian variation in NREMS was eliminated. The phase reversal of REMS to the dark period by the lesion suggests that REMS timing is independently linked to the function of MBH NPY receptor-expressing neurons and is not dependent on NREMS pattern, which was altered but not phase reversed by the lesion. Sleep-wake patterns were altered in controls by restricting feeding to the light period, but were not altered in NPY-SAP rats by restricting feeding to either the light or dark period, indicating that disturbed sleep-wake patterns in lesioned rats were not secondary to changes in food intake. Sleep abnormalities persisted even after hyperphagia abated during the static phase of the lesion. Results suggest that the MBH is required for the essential task of integrating sleep-wake and feeding rhythms, a function that allows animals to accommodate changeable patterns of food availability. NPY receptor-expressing neurons are key components of this integrative function. arcuate nucleus; NPY-saporin; obesity; rapid eye movement sleep FEEDING AND VIGILANCE (sleep-wake) states are rhythmically expressed across the circadian cycle, and their rhythms are highly integrated (3,64,75). Integration of sleep-wake and feeding rhythms is of fundamental importance for survival. Indeed, a wakeful state is an intrinsic requirement for feeding and foraging behavior, and, in a changeable environment, only close communication between these particular rhythms would permit an animal to respond adaptively and opportunistically to changing patterns of food availability. Although the suprachiasmatic nucleus of the hypothalamus (SCN) has an acknowledged role in establishing and maintaining circadian rhythms (47,63,83), including sleep-wake rhythms (15), entrainment of circadian food-anticipatory rhythms does not require the SCN (79,82), supporting the possibility that integration of sleep-wake and feeding also occurs outside the SCN. Furthermore, integration of physiological signals required to derive rhythms compatible with homeostatic requirements is likely to occur outside the SCN (6,48,75), as this arrangement would provide maximum flexibility for responding to varying challenges.Surprisingly few experiments have attempted to determine sites responsible for integration of sleep and feeding rhythms. However, a large body o...

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Brain neuropeptide Y: An integrator of endocrine, metabolic and behavioral processes

Cited by 148 publications

References 44 publications

Presynaptic and Postsynaptic Actions and Modulation of Neuroendocrine Neurons by a New Hypothalamic Peptide, Hypocretin/Orexin

Presynaptic and Postsynaptic Actions and Modulation of Neuroendocrine Neurons by a New Hypothalamic Peptide, Hypocretin/Orexin

Adrenal Steroid Receptors: Interactions with Brain Neuropeptide Systems in Relation to Nutrient Intake and Metabolism

Circadian integration of sleep-wake and feeding requires NPY receptor-expressing neurons in the mediobasal hypothalamus

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