Roles of orexins in the regulation of body weight homeostasis

Sakurai, Takeshi

doi:10.1016/j.orcp.2013.12.001

Cited by 38 publications

(31 citation statements)

References 58 publications

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“…Orexins (also called hypocretins) are neuropeptides originally isolated in rats (Sakurai, 2014), that have since been identified in several fish species. The first direct evidence of an orexigenic action of orexins was shown via intracerebroventricular (ICV) injections in goldfish (Volkoff et al, 1999).…”

Section: Hormones Involved In Food Intakementioning

confidence: 99%

The Neuroendocrine Regulation of Food Intake in Fish: A Review of Current Knowledge

2016

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Fish are the most diversified group of vertebrates and, although progress has been made in the past years, only relatively few fish species have been examined to date, with regards to the endocrine regulation of feeding in fish. In fish, as in mammals, feeding behavior is ultimately regulated by central effectors within feeding centers of the brain, which receive and process information from endocrine signals from both brain and peripheral tissues. Although basic endocrine mechanisms regulating feeding appear to be conserved among vertebrates, major physiological differences between fish and mammals and the diversity of fish, in particular in regard to feeding habits, digestive tract anatomy and physiology, suggest the existence of fish- and species-specific regulating mechanisms. This review provides an overview of hormones known to regulate food intake in fish, emphasizing on major hormones and the main fish groups studied to date.

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Section: Hormones Involved In Food Intakementioning

confidence: 99%

The Neuroendocrine Regulation of Food Intake in Fish: A Review of Current Knowledge

2016

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“…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).…”

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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 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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“…80,103 Recent rodent studies have unveiled novel downstream effects of ONs. The amygdala is the prime target of the LHA ONs, and the stria terminalis accounts for much of the connectivity between the amygdala and the VMH.…”

Section: 58mentioning

confidence: 99%

“…80,97,103 In addition to the robust connectivity between the LHA and the limbic system, data supporting it as a DBS target include the modulatory effects of DBS on the resting metabolic rate in patients, 104 the recent discovery of amino acid-sensing pathways that connect the stomach to the LHA, 97 and the discovery of obesity-related genes expressed exclusively by ONs in the LHA. 103 Because the ONs of the LHA control diet-induced thermogenesis, reward circuits, energy homeostasis, and satiety, 80 the LHA continues to be the target of choice for addressing obesity due to metabolic dysregulation (in peripheral and central areas), genetics, or food addiction.…”

Section: 21196mentioning

confidence: 99%

Deep brain stimulation for obesity: past, present, and future targets

Dupré¹,

Tomycz²,

Oh³

et al. 2015

FOC

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The authors review the history of deep brain stimulation (DBS) in patients for treating obesity, describe current DBS targets in the brain, and discuss potential DBS targets and nontraditional stimulation parameters that may improve the effectiveness of DBS for ameliorating obesity. Deep brain stimulation for treating obesity has been performed both in animals and in humans with intriguing preliminary results. The brain is an attractive target for addressing obesity because modulating brain activity may permit influencing both sides of the energy equation—caloric intake and energy expenditure.

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Roles of orexins in the regulation of body weight homeostasis

Cited by 38 publications

References 58 publications

The Neuroendocrine Regulation of Food Intake in Fish: A Review of Current Knowledge

The Neuroendocrine Regulation of Food Intake in Fish: A Review of Current Knowledge

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

Deep brain stimulation for obesity: past, present, and future targets

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