Orexin-A and leptin change inversely in fasting non-obese subjects

Kobashi, Gén; Matsumoto, Yoshiaki; Nishikata, Hiroaki; Kawai, Keisuke; Nozaki, Tomoyoshi; Takii, Masato; Sogawa, Hiroshi; Kubo, Chiharu

doi:10.1530/eje.0.1440645

Cited by 86 publications

(47 citation statements)

References 30 publications

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“…Thus, orexin cells are somehow sensing the animal's nutritional state, and OXA is released in response to nutritional depletion. In support of this idea, we found a significant increase in plasma OXA level in fasted lean rats similar to that reported in humans (14,15). The origin of plasma OXA was not identified; however, in light of the present findings, one potential source is the pancreatic islets.…”

Section: Discussionsupporting

confidence: 91%

supporting

confidence: 53%

“…Endocrine cells in the gastric and intestinal mucosa (12,13), as well as in the pancreas (12), also contain orexins; therefore, orexins may function as circulating hormones and/or paracrine or autocrine transmitters. The presence of OXA in human plasma supports this idea (14,15).Little is known about the regulation and role of the orexins in the endocrine pancreas. We have previously shown that OXA and orexin receptor immunoreactivity is displayed by the insulin-secreting ␤-cells in the rat pancreas (12).…”

mentioning

confidence: 81%

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Glucose Regulates the Release of Orexin-A From the Endocrine Pancreas

2003

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Orexins (hypocretins) are novel neuropeptides that appear to play a role in the regulation of energy balances. Orexin-A (OXA) increases food intake in rodents, and fasting activates OXA neurons in both the lateral hypothalamic area and gut. OXA is also found in the endocrine pancreas; however, little is known about its release or functional significance. In this study, we show that depolarizing stimuli evoke the release of OXA from rat pancreatic islets in a calcium-dependent manner. Moreover, OXA release is stimulated by low glucose (2.8 mmol/l), similar to glucagon secretion, and inhibited by high glucose (16.7 mmol/l). Fasting increases plasma OXA, supporting the idea that orexin is released in response to hypoglycemia. Cells that secrete glucagon and insulin contain OXA and both cell types express orexin receptors. OXA increases glucagon secretion and decreases glucose-stimulated insulin release from isolated islets. OXA infusion increases plasma glucagon and glucose levels and decreases plasma insulin in fasted rats. We conclude that orexin-containing islet cells, like those in the brain and gut, are glucosensitive and part of a network of glucose "sensing" cells that becomes activated when blood glucose levels fall. OXA may modulate islet hormone secretion to maintain blood glucose levels during fasting. Diabetes 52: 111-117, 2003 O rexins (hypocretins) are novel neuropeptides that play a role in arousal and the regulation of energy balances (1-3). Orexin-A (OXA) and -B are 33-and 28-residue peptides, respectively, that are isolated from the rat hypothalamus and named for their ability to stimulate feeding when injected into the brain (2). Their common precursor, prepro-orexin, is expressed in a specific population of neurons in and around the lateral hypothalamic area (LHA) (2), a region classically implicated in the control of mammalian feeding behavior (4). The LHA contains glucosensitive neurons that are stimulated by falls in circulating glucose (5) and inhibited by prandial signals, such as the presence of food in the gut and/or a rise in portal glucose concentration (4). Previous studies have suggested that orexin neurons might correspond to this neuronal population, since orexin neurons are activated by hypoglycemia (6) and increased hypothalamic prepro-orexin mRNA levels are observed in response to fasting (1,7); however, glucosensitive neurons do not contain OXA (8). They are excited by the peptide (8), implying that orexin acts as a neuromodulator at glucosensitive cells, stimulating them under conditions of hunger.Glucosensitive neurons are also found in regions outside the hypothalamus, including the nucleus of the solitary tract (NTS) (9) and enteric nervous system (ENS) (10). The NTS relays visceral afferent signals to the LHA (8). Orexin fibers are distributed extensively in the NTS (11), and glucosensitive neurons are activated by the same conditions that stimulate orexin neurons in the LHA (6). The ENS participates in the regulation of food intake by directly sensing, integrating, and reg...

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Section: Discussionsupporting

confidence: 91%

supporting

confidence: 53%

mentioning

confidence: 81%

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Glucose Regulates the Release of Orexin-A From the Endocrine Pancreas

2003

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“…Also recently, a bidirectional association between plasma concentration of leptin and orexin as regards nicotine craving was demonstrated (von der Goltz et al, 2010). Such inverse correlation between leptin and orexin plasma levels was also found both in obese and non-obese participants (Komaki et al, 2001 andBronsky et al 2007). However, in AN-R patients studied by us, such an association was observed only initially and has not hold during the course of treatment .…”

Section: Correlation Between Leptin (Lep) and Orexin A (Oxa) Plasma Lmentioning

confidence: 89%

“…A number of observations point to an increase in the orexin A level during fasting and weight loss, and a decrease during weight gain. Komaki et al (2001) reported an increase in orexin A plasma levels in adult fasting, non-obese participants during 10 days of fasting which was followed by a reduction in orexin A plasma levels during subsequent refeeding. Bronsky et al (2007) observed a significant increase in orexin A plasma levels after a decrease of BMI from about 28 kg/m 2 to 26 kg/m 2 in fasting obese children.…”

Section: Orexin a (Oxa) Plasma Level In Patients Suffering From Anorementioning

confidence: 95%

Orexigenic and Anorexigenic Peptides in Restrictive Type of Anorexia Nervosa

Janas–Kozik¹,

Stachowicz²,

Janas³

et al. 2012

Relevant Topics in Eating Disorders

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Variants of the orexin2/hcrt2 receptor gene identified in patients with excessive daytime sleepiness and patients with Tourette's syndrome comorbidity

Thompson

Comings²,

Abu-Ghazalah

et al. 2004

American J of Med Genetics Pt B

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The orexin-2/hypocretin-2 (OX2R) receptor gene is mutated in canine narcolepsy and disruption of the prepro-orexin/hypocretin ligand gene results in both an animal model of narcolepsy and sporadic cases of the human disease. This evidence suggests that the structure of the OX2R gene, and its homologue, the OX1R gene, both members of the G protein-coupled receptor (GPCR) family, and the gene encoding the peptide ligands, the prepro-orexin/hypocretin gene, may be variables in the etiology of sleep disorders. We report a single stranded conformational polymorphism (SSCP) analysis of the coding regions of these genes in idiopathic sleep disorder patients diagnosed with excessive daytime sleepiness (EDS) (n = 28), narcolepsy (n = 28), Tourette's syndrome/chronic vocal or motor tic disorder (n = 70), and control subjects (n = 110). Two EDS patients showed a Pro11Thr change. One Tourette's syndrome patient was found to have a Pro10Ser alteration. The Pro10Ser and Pro11Thr variants were not found in non-disease populations. Analysis of the ability of the mutant receptors to mobilize calcium compared to the wild-type receptor in response to orexin agonists indicated that they resulted in decreased potency at high (etaM) concentrations of orexin ligands. Further work is warranted to study the variability of the orexin/hypocretin system in a variety of disorders characterized by EDS.

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Orexin-A and leptin change inversely in fasting non-obese subjects

Cited by 86 publications

References 30 publications

Glucose Regulates the Release of Orexin-A From the Endocrine Pancreas

Glucose Regulates the Release of Orexin-A From the Endocrine Pancreas

Orexigenic and Anorexigenic Peptides in Restrictive Type of Anorexia Nervosa

Variants of the orexin2/hcrt2 receptor gene identified in patients with excessive daytime sleepiness and patients with Tourette's syndrome comorbidity

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