The effect of the orexins on food intake: comparison with neuropeptide Y, melanin-concentrating hormone and galanin

Edwards, C. M. B.; Abusnana, Salah; Sunter, David; Murphy, Kevin G.; Ghatei, Mohammed A.; Bloom, Stephen R.

doi:10.1677/joe.0.160r007

Cited by 406 publications

(261 citation statements)

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“…Role m In satiety; m water reward (Horger et al, 1999;Kernie et al, 2000;Nakagawa et al, 2003); improvement in glucose metabolism (Tonra et al, 1999;Nakagawa et al, 2000;Ono et al, 2000) m Drug reward (Horger et al, 1999) K BDNF in mesolimbic pathways regulates appetitive behavior (Eisch et al, 2003;Itoh et al, 2004); BDNF within hypothalamus regulates energy balance by enhancing catabolic processes (Xu et al, 2003) K BDNF may play a role in behavioral sensitization to drugs (Guillin et al, 2001) and potentially to palatable food via its dopaminergic and opioidergic (Siuciak et al, 1994;Siuciak et al, 1995) effects Repeated exposure kIn the hippocampus (Molteni et al, 2002;Molteni et al, 2004) m In mesocorticolimbic areas including, hypothalamus (Meredith et al, 2002;Butovsky et al, 2005); m and upregulation of BDNF receptors during withdrawal (Toda et al, 2002;Grimm et al, 2003); incubation of drug craving, accompanied by m in BDNF (Grimm et al, 2003) BDNF gene knockout animals m In food intake and obesity (Lyons et al, 1999;Kernie et al, 2000;Rios et al, 2001;Xu et al, 2003) k Drug reward (Hall et al, 2003;Horger et al, 1999) Orexin m Food intake (Edwards et al, 1999;Harris et al, 2005) Relapse to drug seeking behavior (Harris et al, 2005) Activated by SGAs ( Ibanez-Rojo et al, 1993;Bencherif et al, 2005) are available, though, to extend preclinical palatable food opioid findings to humans. Neuroimaging studies in obese people reported in...…”

Section: Bdnfmentioning

confidence: 99%

“…Through its hypothalamic effects, BDNF controls energy balance by enhancing catabolic processes (Xu et al, 2003). Similarly important are the actions of orexin neurons, situated in the LH and projecting to the NAc and VTA , to control food intake (Edwards et al, 1999;Harris et al, 2005) as well as drug reward and craving (Harris et al, 2005). In fact, a finding of a correlation between SGAs weight liability and the degree of LH orexin neurons stimulation ) is provocative and may offer important insights into homeostatic dysregulation associated with antipsychotic agents.…”

Section: Bdnfmentioning

confidence: 99%

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Food Intake and Reward Mechanisms in Patients with Schizophrenia: Implications for Metabolic Disturbances and Treatment with Second-Generation Antipsychotic Agents

Elman

Borsook

Lukas

2006

Neuropsychopharmacol

133

142

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Obesity is highly prevalent among patients with schizophrenia and is associated with detrimental health consequences. Although excessive consumption of fast food and pharmacotherapy with such second-generation antipsychotic agents (SGAs) as clozapine and olanzapine has been implicated in the schizophrenia/obesity comorbidity, the pathophysiology of this link remains unclear. Here, we propose a mechanism based on brain reward function, a relevant etiologic factor in both schizophrenia and overeating. A comprehensive literature search on neurobiology of schizophrenia and of eating behavior was performed. The collected articles were critically reviewed and relevant data were extracted and summarized within four key areas: (1) energy homeostasis, (2) food reward and hedonics, (3) reward function in schizophrenia, and (4) metabolic effects of the SGAs. A mesolimbic hyperdopaminergic state may render motivational/incentive reward system insensitive to low salience/palatability food. This, together with poor cognitive control from hypofunctional prefrontal cortex and enhanced hedonic impact of food, owing to exaggerated opioidergic drive (clinically manifested as pain insensitivity), may underlie unhealthy eating habits in patients with schizophrenia. Treatment with SGAs purportedly improves dopamine-mediated reward aspects, but at the cost of increased appetite and worsened or at least not improved opiodergic capacity. These effects can further deteriorate eating patterns. Pathophysiological and therapeutic implications of these insights need further validation via prospective clinical trials and neuroimaging studies. INTRODUCTIONObesity has reached pandemic proportions and it is rapidly surpassing smoking as a number one killer in the industrialized world (Sturm, 2002;Skidmore and Yarnell, 2004). Its annual cost to the American society is staggering, and is estimated to be around $117 billion owing to related illnesses and loss of productivity (National Institute of Diabetes and Digestive and Kidney Diseases, 2005).In schizophrenia, obesity is twice as prevalent as in the general public, afflicting over half this patient population (Allison et al, 1999a;Dixon et al, 2000; American Diabetes Association, 2004;Marder et al, 2004;Wirshing, 2004). Besides negative psychosocial impacts (distorted selfesteem and societal stigmatization) and medications noncompliance, schizophrenics appear to be particularly susceptible to the detrimental medical sequelae of obesity such as the 'Metabolic Syndrome', which is a cluster of cardiovascular risk factors, including abdominal adiposity, insulin resistance, impaired, glucose tolerance, dyslipidemia, and hypertension (McKee et al, 1986;Mukherjee et al, 1996;Brown et al, 2000;Haupt and Newcomer, 2002;Ryan and Thakore, 2002;Ryan et al, 2003;Holt et al, 2004;Kohen, 2004;Marder et al, 2004;Lieberman et al, 2005).Excessive body weight gain (BWG) could be attributed to a constellation of endocrine, molecular, genetic, demographic, and lifestyle-related factors. Provided that a common tra...

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Section: Bdnfmentioning

confidence: 99%

Section: Bdnfmentioning

confidence: 99%

Food Intake and Reward Mechanisms in Patients with Schizophrenia: Implications for Metabolic Disturbances and Treatment with Second-Generation Antipsychotic Agents

Elman

Borsook

Lukas

2006

Neuropsychopharmacol

133

142

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“…Orexin (also known as hypocretin) is a neuropeptide that has been reported to play a role in the regulation of feeding, drinking, body temperature, general activity (Lubkin and Stricker-Krongrad, 1998;Edwards et al, 1999;Hagan et al, 1999;Kunii et al, 1999;Mondal et al, 1999;Piper et al, 2000;Estabrooke et al, 2001;Hungs et al, 2001;Yoshimichi et al, 2001;Kotz et al, 2002;Berthoud et al, 2005), energy homeostasis (Mintz et al, 2001), stimulation of gastric secretion in rats (Takahashi et al, 1999), increasing metabolic rate in rats (Lubkin and Stricker-Krongard, 1998), altering luteinising hormone release in rats (Pu et al, 1998) and in the regulation of the sleepwake cycle specifically associated with increased wakefulness and inhibition of REM sleep (Sakurai et al, 1998;Chemelli et al, 1999;Siegel, 1999;Bourgin et al, 2000;Kilduff and Peyron, 2000;Thannickal et al, 2000;van den Pol, 2000).…”

Section: Introductionmentioning

confidence: 99%

Distribution of orexinergic neurons and their terminal networks in the brains of two species of African mole rats

Bhagwandin

Fuxé

Bennett

et al. 2011

Journal of Chemical Neuroanatomy

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The distribution of orexinergic cell bodies and terminal networks within the brains of two species of African mole rat (Cape-dune mole rat -Bathyergus suillus and highveld mole rat -Cryptomys hottentotus) were identified using immunohistochemistry for Orexin-A.The aim of the study was to investigate possible differences in the nuclear complement and terminal distribution of this system by comparing those of the mole rats to published studies of other rodents and mammals. The wild-caught mole rats used in this study live a subterranean lifestyle and are well known for their regressed visual system, which may lead to the prediction of differences in the distribution of the cell bodies and the terminal networks; however, we found that both species of mole rat displayed orexinergic nuclei limited to the hypothalamus in regions similar to those previously reported for other rodent and mammalian species. No immunoreactive neurons could be identified, in either species of mole rat within the anterior hypothalamic paraventricular nucleus, as has been reported for Murid rodents. The terminal networks, while remaining similar between the species, are more strongly expressed in the Cape-dune mole rat than in the highveld mole rat.

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“…Hypocretin/orexin, when injected intracerebroventricularly, increases food intake, energy expenditure, and locomotor activity [1,7,10]. Thus, hypocretin deficiency decreases appetite and energy expenditure, but the latter may have larger impact, resulting in a positive weight gain.…”

Section: Introductionmentioning

confidence: 99%

Sex difference in body weight gain and leptin signaling in hypocretin/orexin deficient mouse models

Fujiki

Yoshida²,

Zhang³

et al. 2006

Peptides

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Recent studies in human and animal models of narcolepsy have suggested that obesity in narcolepsy may be due to deficiency of hypocretin signaling, and is also under the influence of environmental factors and the genetic background. In the current study, using two hypocretin/orexin deficient narcoleptic mouse models (i.e. prepro-orexin knockout (KO) and orexin/ataxin-3 transgenic (TG) mice) with cross-sectional assessments, we have further analyzed factors affecting obesity. We found that both KO and TG narcoleptic mice with mixed genetic backgrounds (N4-5, 93.75-96.88 % genetic composition of C57BL/6) tended to be heavier than wild type (WT) mice of 100 to 200 days old. The body weight of heterozygous mice was intermediate between those of KO and WT mice. Obesity was more prominent in females in both KO and TG narcoleptic mice and was associated with higher serum leptin levels, suggesting a partial leptin resistance. Obesity is less prominent in the congenic TG narcoleptic mice, but is still evident in females. Our results confirmed that hypocretin/orexin ligand deficiency is one of the critical factors for the obese tendency in narcolepsy. However, multiple factors are also likely to affect this phenotype, and a gender specific alteration of leptin-hypocretin signaling may be involved.

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The effect of the orexins on food intake: comparison with neuropeptide Y, melanin-concentrating hormone and galanin

Cited by 406 publications

References 19 publications

Food Intake and Reward Mechanisms in Patients with Schizophrenia: Implications for Metabolic Disturbances and Treatment with Second-Generation Antipsychotic Agents

Food Intake and Reward Mechanisms in Patients with Schizophrenia: Implications for Metabolic Disturbances and Treatment with Second-Generation Antipsychotic Agents

Distribution of orexinergic neurons and their terminal networks in the brains of two species of African mole rats

Sex difference in body weight gain and leptin signaling in hypocretin/orexin deficient mouse models

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