Relationship of body weight to the lateral hypothalamic feeding syndrome.

Powley, Terry L.; Keesey, Richard E.

doi:10.1037/h0028390

Cited by 292 publications

(135 citation statements)

References 13 publications

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“…This may in part be addressed by examining the role of the lateral hypothalamus in general. It has been implicated in the regulation of feeding (Powley and Keesey, 1970;van den Pol, 1982) and detection of circulating glucose levels (Oomura, 1983). This is consistent with suggestions that hypocretin injections may enhance food intake .…”

Section: Hypocretin Function In Spinal Cordsupporting

confidence: 75%

Hypothalamic Hypocretin (Orexin): Robust Innervation of the Spinal Cord

1999

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Hypocretin (orexin) is synthesized by neurons in the lateral hypothalamus and has been reported to increase food intake and regulate the neuroendocrine system. In the present paper, long descending axonal projections that contain hypocretin were found that innervate all levels of the spinal cord from cervical to sacral segments, as studied in mouse, rat, and human spinal cord and not previously described. High densities of axonal innervation are found in regions of the spinal cord related to modulation of sensation and pain, notably in the marginal zone (lamina 1). Innervation of the intermediolateral column and lamina 10 as well as strong innervation of the caudal region of the sacral cord suggest that hypocretin may participate in the regulation of both the sympathetic and parasympathetic parts of the autonomic nervous system. Doublelabeling experiments in mice combining retrograde transport of diamidino yellow after spinal cord injections and immunocytochemistry support the concept that hypocretin-immunoreactive fibers in the cord originate from the neurons in the lateral hypothalamus. Digital-imaging physiological studies with fura-2 detected a rise in intracellular calcium in response to hypocretin in cultured rat spinal cord neurons, indicating that spinal cord neurons express hypocretin-responsive receptors. A greater number of cervical cord neurons responded to hypocretin than another hypothalamo-spinal neuropeptide, oxytocin. These data suggest that in addition to possible roles in feeding and endocrine regulation, the descending hypocretin fiber system may play a role in modulation of sensory input, particularly in regions of the cord related to pain perception and autonomic tone.

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Section: Hypocretin Function In Spinal Cordsupporting

confidence: 75%

Hypothalamic Hypocretin (Orexin): Robust Innervation of the Spinal Cord

1999

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“…Lesions of the LH cause a longlasting reduction in body weight and food intake in both male and female rodents (Powley and Keesey, 1970;van den Pol, 1982). In addition to the cell bodies (Gautvik et al, 1996;de Lecea et al, 1998;Sakurai et al, 1998) (Fig.…”

Section: Calcium Response To Hypocretinmentioning

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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“…In the central nervous system, orexins are produced exclusively by a small group of neurons in the lateral hypothalamic area (5,8,10,21,24), a region classically implicated in the control of feeding (23). Orexin mRNA expression is increased by fasting in rodents (19,24), and OXA increases food intake (presumably via OX1R) when injected into the third ventricle or lateral hypothalamus (6,24,25,30).…”

mentioning

confidence: 99%

Localization and effects of orexin on fasting motility in the rat duodenum

Näslund

Ehrström

et al. 2002

American Journal of Physiology-Gastrointestinal and Liver Physi

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Nä slund, E., M. Ehrströ m, J. Ma, P. M. Hellströ m, and A. L. Kirchgessner. Localization and effects of orexin on fasting motility in the rat duodenum. Am J Physiol Gastrointest Liver Physiol 282: G470-G479, 2002; 10.1152/ajpgi. 00219.2001 and orexin B (OXB)] are novel neuropeptides that increase food intake in rodents. The aim of this study was to determine the distribution of orexin and orexin receptors (OX1R and OX2R) in the rat duodenum and examine the effects of intravenous orexin on fasting gut motility. OXA-like immunoreactivity was found in varicose nerve fibers in myenteric and submucosal ganglia, the circular muscle, the mucosa, submucosal and myenteric neurons, and numerous endocrine cells of the mucosa. OXA neurons displayed choline acetyltransferase immunoreactivity, and a subset contained vasoactive intestinal peptide. OXA-containing endocrine cells were identified as enterochromaffin (EC) cells based on the presence of 5-hydroxytryptamine immunoreactivity. OX1R was expressed by neural elements of the gut, and EC cells expressed OX2R. OXA at 100 and 500 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 significantly increased the myoelectric motor complex (MMC) cycle length compared with saline. Similarly, OXB increased the MMC cycle length at 100 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 , but there was no further effect at 500 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 . We postulate that orexins may affect the MMC through actions on enteric neurotransmission after being released from EC cells and/or enteric neurons. migrating motor complex; orexin receptors; enteric ganglia; enterochromaffin cells OREXINS ARE NOVEL NEUROPEPTIDES that appear to play a role in the regulation of feeding, arousal, and energy homeostasis (for review, see Ref. 29). The orexins consist of orexin A (OXA) and orexin B (OXB) that are proteolytically derived from the same 130-amino acid residue preproorexin precursor protein. To date, two orexin receptors (OX1R and OX2R) have been described that belong to the G protein-coupled receptor superfamily, with a proposed seven-transmembrane topology (24). According to in vitro binding and functional assays, OX1R is selective for OXA, and OX2R is nonselective for both OXA and OXB peptides (24).

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Relationship of body weight to the lateral hypothalamic feeding syndrome.

Cited by 292 publications

References 13 publications

Hypothalamic Hypocretin (Orexin): Robust Innervation of the Spinal Cord

Hypothalamic Hypocretin (Orexin): Robust Innervation of the Spinal Cord

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

Localization and effects of orexin on fasting motility in the rat duodenum

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