Plasma orexin‐A levels in postmenopausal women: possible interaction with estrogen and correlation with cardiovascular risk status

El-Sedeek, MShEA; Korish, Aida A.; Deef, MM

doi:10.1111/j.1471-0528.2009.02474.x

Cited by 31 publications

(31 citation statements)

References 30 publications

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“…We provide evidence that such mechanism, by being under the negative control of leptin, may also contribute to obesity and some of its pathological consequences. Because a possible sex difference occurs in the regulation of plasma OX-A levels in humans (28,29,31) and in the POMC-driven regulation of energy expenditure and obesity in mice (30), we performed our study exclusively in male subjects. In particular, we show that OX-A acts via DAGLα-catalyzed biosynthesis of 2-AG, which then acts as an autocrine mediator on OX-1R/CB 1 R-expressing POMC neurons of the ARC to inhibit STAT3 activity and subsequently repress POMC expression and the release of the anorectic peptide, α-MSH.…”

Section: Discussionmentioning

confidence: 99%

“…Next, we explored whether higher levels of OX-A correlate with lower levels of α-MSH in subjects who exhibit clinical markers of obesity. Because a possible correlation between estrogen and plasma OX-A levels has been described in humans (28,29), and a sex difference occurs in the POMC-driven regulation of energy expenditure and obesity in mice (30), we tested this hypothesis exclusively in male subjects (n = 50) who had suffered from obesity for at least 5 y in comparison with n = 50 male healthy, normal-weight, volunteers. Clinical, functional, and biochemical data were obtained from each patient at the baseline, and secondary causes of obesity were excluded.…”

Section: Ox-a and α-Msh Plasma Levels Are Inversely Correlated In Severementioning

confidence: 99%

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Orexin-A represses satiety-inducing POMC neurons and contributes to obesity via stimulation of endocannabinoid signaling

Morello

Imperatore

Palomba

et al. 2016

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

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In the hypothalamic arcuate nucleus (ARC), proopiomelanocortin (POMC) neurons and the POMC-derived peptide α-melanocytestimulating hormone (α-MSH) promote satiety. POMC neurons receive orexin-A (OX-A)-expressing inputs and express both OX-A receptor type 1 (OX-1R) and cannabinoid receptor type 1 (CB 1 R) on the plasma membrane. OX-A is crucial for the control of wakefulness and energy homeostasis and promotes, in OX-1R-expressing cells, the biosynthesis of the endogenous counterpart of marijuana's psychotropic and appetite-inducing component Δ 9 -tetrahydrocannabinol, i.e., the endocannabinoid 2-arachidonoylglycerol (2-AG), which acts at CB 1 R. We report that OX-A/OX-1R signaling at POMC neurons promotes 2-AG biosynthesis, hyperphagia, and weight gain by blunting α-MSH production via CB 1 R-induced and extracellularsignal-regulated kinase 1/2 activation-and STAT3 inhibitionmediated suppression of Pomc gene transcription. Because the systemic pharmacological blockade of OX-1R by SB334867 caused anorectic effects by reducing food intake and body weight, our results unravel a previously unsuspected role for OX-A in endocannabinoid-mediated promotion of appetite by combining OX-induced alertness with food seeking. Notably, increased OX-A trafficking was found in the fibers projecting to the ARC of obese mice (ob/ob and high-fat diet fed) concurrently with elevation of OX-A release in the cerebrospinal fluid and blood of mice. Furthermore, a negative correlation between OX-A and α-MSH serum levels was found in obese mice as well as in human obese subjects (body mass index > 40), in combination with elevation of alanine aminotransferase and γ-glutamyl transferase, two markers of fatty liver disease. These alterations were counteracted by antagonism of OX-1R, thus providing the basis for a therapeutic treatment of these diseases.hypocretin-1 | cannabinoid type 1 receptor | 2-arachidonoylglycerol | α-melanocyte-stimulating hormone | hypothalamus E merging anatomical, biochemical, and pharmacological evidence supports a functional interaction between endocannabinoids and orexin-A (OX-A) (also known as hypocretin-1) in the hypothalamic regulation of appetite, energy expenditure, and metabolism (1). In hypothalamic neurons, the endocannabinoid 2-arachidonylglycerol (2-AG) is under the negative control of leptin (2) and acts through the cannabinoid receptor type 1 (CB 1 R) to promote appetite by activating several intracellular pathways, including mitogen-activated protein kinases of the extracellularsignal-regulated kinase (ERK) family (3). OX-A is an orexigenic neuropeptide expressed by neurons of the lateral hypothalamus (LH), which acts through the OX-A receptor type 1 (OX-1R) (4). Activation of OX-1R by OX-A signaling has been found to affect CB 1 R function by stimulating 2-AG biosynthesis via the phospholipase C/diacylglycerol lipase α (PLC/DAGL) pathway (5) and by enhancing ERK1/2 phosphorylation and activity in cells expressing both OX-1R and CB 1 R (6, 7). Proopiomelanocortin (POMC)-containing neurons represent t...

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Section: Discussionmentioning

confidence: 99%

Section: Ox-a and α-Msh Plasma Levels Are Inversely Correlated In Severementioning

confidence: 99%

Orexin-A represses satiety-inducing POMC neurons and contributes to obesity via stimulation of endocannabinoid signaling

Morello

Imperatore

Palomba

et al. 2016

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

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“…In humans, plasma orexin level correlates with age, with lower levels in subjects under 40, and higher levels among those aged 60 or more (Matsumura et al, 2002). In women, plasma orexin increases significantly during menopause (El-Sedeek et al, 2010). Among menopausal women, those receiving hormone replacement therapy have lower levels of plasma orexin than those receiving placebo (El-Sedeek et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…In women, plasma orexin increases significantly during menopause (El-Sedeek et al, 2010). Among menopausal women, those receiving hormone replacement therapy have lower levels of plasma orexin than those receiving placebo (El-Sedeek et al, 2010). Plasma orexin is known to increase after weight loss in obese children and in lean and obese adults (Bronsky et al, 2007; Heinonen et al, 2005; Komaki et al, 2001), suggesting that increase in plasma orexin is not inconsistent with orexin involvement in age-related weight loss.…”

Section: Discussionmentioning

confidence: 99%

Sleep disorders, obesity, and aging: The role of orexin

Nixon

Mavanji

Butterick

et al. 2015

Ageing Research Reviews

112

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The hypothalamic neuropeptides orexin A and B (hypocretin 1 and 2) are important homeostatic mediators of central control of energy metabolism and maintenance of sleep/wake states. Dysregulation or loss of orexin signaling has been linked to narcolepsy, obesity, and age-related disorders. In this review, we present an overview of our current understanding of orexin function, focusing on sleep disorders, energy balance, and aging, in both rodents and humans. We first discuss animal models used in studies of obesity and sleep, including loss of function using transgenic or viral-mediated approaches, gain of function models using exogenous delivery of orexin receptor agonist, and naturally-occurring models in which orexin responsiveness varies by individual. We next explore rodent models of orexin in aging, presenting evidence that orexin loss contributes to age-related changes in sleep and energy balance. In the next section, we focus on clinical importance of orexin in human obesity, sleep, and aging. We include discussion of orexin loss in narcolepsy and potential importance of orexin in insomnia, correlations between animal and human studies of age-related decline, and evidence for orexin involvement in age-related changes in cognitive performance. Finally, we present a summary of recent studies of orexin in neurodegenerative disease. We conclude that orexin acts as an integrative homeostatic signal influencing numerous brain regions, and that this pivotal role results in potential dysregulation of multiple physiological processes when orexin signaling is disrupted or lost.

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“…Estrogen receptors are found on the trigeminal ganglion as well as on sensory neurons, which makes them susceptible for estrogenic modulation [55]. Further, it was demonstrated that higher orexin A blood levels are associated with a state of hypoestrogenism (menopause) [56].…”

Section: Cluster Headachementioning

confidence: 98%

Sex Hormones and Primary Headaches Other than Migraine

Lieba‐Samal

Wöber

2011

Curr Pain Headache Rep

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The relation between sex hormones and migraine has been examined in a series of studies, leading to the definitions of pure menstrual migraine and menstrually-related migraine. The relation between sex hormones and other types of primary headache has been studied less extensively, but there is at least some evidence that hormones in general, and menstruation, pregnancy, or menopause in particular, also impact these disorders. This article reviews the available literature on changes of tension-type headache, cluster headache, other trigeminal autonomic cephalalgias, and hemicrania continua during women's reproductive periods.

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Plasma orexin‐A levels in postmenopausal women: possible interaction with estrogen and correlation with cardiovascular risk status

Cited by 31 publications

References 30 publications

Orexin-A represses satiety-inducing POMC neurons and contributes to obesity via stimulation of endocannabinoid signaling

Orexin-A represses satiety-inducing POMC neurons and contributes to obesity via stimulation of endocannabinoid signaling

Sleep disorders, obesity, and aging: The role of orexin

Sex Hormones and Primary Headaches Other than Migraine

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