Involvement of Prolactin‐Releasing Peptide in the Activation of Oxytocin Neurones in Response to Food Intake

Yamashita, M; Takayanagi, Yuki; Yoshida, Masahide; Nishimori, Katsuhiko; Kusama, Mikio; Onaka, Tatsushi

doi:10.1111/jne.12019

Cited by 46 publications

(49 citation statements)

References 70 publications

(123 reference statements)

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“…Furthermore, OTR and OT null mice fail to consume more chow relative to wild-type or littermate control mice [90,91,121]. Studies indicate that OTR null mice still consume larger meals during the dark cycle [130] despite showing no change in overall chow intake. In addition, removal of approximately 95% of PVN OT neurons following Cre-mediated diphtheria toxin administration in adult oxytocin-Ires-Cre mice failed to impact intake of chow or HFDs [87].…”

Section: Intact Response To Ot Despite Impaired Leptin Signalingmentioning

confidence: 89%

“…Decreases in OT signaling have been shown to be associated with obesity and reductions in energy expenditure [32,87,90,91,134], including defects in sympathetic nervous system activity, brown adipose tissue (BAT) thermogenesis [90,91,134], and oxygen consumption [32,87], in the absence of hyperphagia in mice [87,90,91,121,130]. In contrast, direct injections of OT into the CNS increased energy expenditure [31,32,108], body temperature [71], and heart rate [71,135] in mice or rats.…”

Section: Effects Of Ot On Energy Expenditurementioning

confidence: 93%

See 1 more Smart Citation

Translational and therapeutic potential of oxytocin as an anti-obesity strategy: Insights from rodents, nonhuman primates and humans

Blevins

Baskin

2015

Physiology & Behavior

128

100

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The fact that more than 78 million adults in the US are considered overweight or obese highlights the need to develop new, effective strategies to treat obesity and its associated complications, including type 2 diabetes, kidney disease and cardiovascular disease. While the neurohypophyseal peptide oxytocin (OT) is well recognized for its peripheral effects to stimulate uterine contraction during parturition and milk ejection during lactation, release of OT within the brain is implicated in prosocial behaviors and in the regulation of energy balance. Previous findings indicate that chronic administration of OT decreases food intake and weight gain or elicits weight loss in diet-induced obese (DIO) mice and rats. Furthermore, chronic systemic treatment with OT largely reproduces the effects of central administration to reduce weight gain in DIO and genetically obese rodents at doses that do not appear to result in tolerance. These findings have now been recently extended to more translational models of obesity showing that chronic subcutaneous or intranasal OT treatment is sufficient to elicit body weight loss in DIO nonhuman primates and pre-diabetic obese humans. This review assesses the potential use of OT as a therapeutic strategy for treatment of obesity in rodents, nonhuman primates, and humans, and identifies potential mechanisms that mediate this effect.

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Section: Intact Response To Ot Despite Impaired Leptin Signalingmentioning

confidence: 89%

Section: Effects Of Ot On Energy Expenditurementioning

confidence: 93%

Translational and therapeutic potential of oxytocin as an anti-obesity strategy: Insights from rodents, nonhuman primates and humans

Blevins

Baskin

2015

Physiology & Behavior

128

100

View full text Add to dashboard Cite

show abstract

“…While our studies specifically targeted the metabolic sensor capability of the MNCs by examining the responses to glucose and insulin, these neurons also are activated in response to feeding (25,35,40), gastric distention (56), activation of vagal afferents (72), and refeeding after an overnight (83) or 48 h fast (35). They also respond to other molecules involved in appetite regulation including leptin (20), ghrelin (18,84), cholecystokinin (23,24), nesfatin (30,37), and prolactin-releasing peptide (83).…”

Section: R451mentioning

confidence: 98%

Supraoptic oxytocin and vasopressin neurons function as glucose and metabolic sensors

Song

Levin

Stevens

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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Neurons in the supraoptic nuclei (SON) produce oxytocin and vasopressin and express insulin receptors (InsR) and glucokinase. Since oxytocin is an anorexigenic agent and glucokinase and InsR are hallmarks of cells that function as glucose and/or metabolic sensors, we evaluated the effect of glucose, insulin, and their downstream effector ATP-sensitive potassium (KATP) channels on calcium signaling in SON neurons and on oxytocin and vasopressin release from explants of the rat hypothalamo-neurohypophyseal system. We also evaluated the effect of blocking glucokinase and phosphatidylinositol 3 kinase (PI3K; mediates insulin-induced mobilization of glucose transporter, GLUT4) on responses to glucose and insulin. Glucose and insulin increased intracellular calcium ([Ca(2+)]i). The responses were glucokinase and PI3K dependent, respectively. Insulin and glucose alone increased vasopressin release (P < 0.002). Oxytocin release was increased by glucose in the presence of insulin. The oxytocin (OT) and vasopressin (VP) responses to insulin+glucose were blocked by the glucokinase inhibitor alloxan (4 mM; P ≤ 0.002) and the PI3K inhibitor wortmannin (50 nM; OT: P = 0.03; VP: P ≤ 0.002). Inactivating K ATP channels with 200 nM glibenclamide increased oxytocin and vasopressin release (OT: P < 0.003; VP: P < 0.05). These results suggest that insulin activation of PI3K increases glucokinase-mediated ATP production inducing closure of K ATP channels, opening of voltage-sensitive calcium channels, and stimulation of oxytocin and vasopressin release. The findings are consistent with SON oxytocin and vasopressin neurons functioning as glucose and "metabolic" sensors to participate in appetite regulation.

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“…Behaviorally, central oxytocin has been reported to delay meal onset (2) and reduce intake of sweet foods (22,27,33). Additionally, previous studies implicate a physiological role for endogenous oxytocin in reducing meal size (7,62). In addition to feeding effects, central oxytocin has potent effects on energy metabolism.…”

mentioning

confidence: 99%

Oxytocin in the ventromedial hypothalamic nucleus reduces feeding and acutely increases energy expenditure

Noble

Billington

Kotz

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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Noble EE, Billington CJ, Kotz CM, Wang C. Oxytocin in the ventromedial hypothalamic nucleus reduces feeding and acutely increases energy expenditure. Am J Physiol Regul Integr Comp Physiol 307: R737-R745, 2014. First published July 2, 2014; doi:10.1152/ajpregu.00118.2014.-Central oxytocin reduces food intake and increases energy expenditure. The ventromedial hypothalamic nucleus (VMN) is associated with energy balance and contains a high density of oxytocin receptors. We hypothesized that oxytocin in the VMN is a negative regulator of energy balance acting to reduce feeding and increase energy expenditure. To test this idea, oxytocin or vehicle was injected directly into the VMN of Sprague-Dawley rats during fasted and nonfasted conditions. Energy expenditure (via indirect calorimetry) and spontaneous physical activity (SPA) were recorded simultaneously. Animals were also exposed to a conditioned taste aversion test, to determine whether oxytocin's effects on food intake were associated with malaise. When food was available during testing, oxytocin-induced elevations in energy expenditure lasted for 1 h, after which overall energy expenditure was reduced. In the absence of food during the testing period, oxytocin similarly increased energy expenditure during the first hour, but differences in 12-h energy expenditure were eliminated, implying that the differences may have been due to the thermic effects of feeding (digestion, absorption, and metabolic processing). Oxytocin acutely elevated SPA and reduced feeding at doses that did not cause a conditioned taste aversion during both the fed and fasted states. Together, these data suggest that oxytocin in the VMN promotes satiety and acutely elevates energy expenditure and SPA and implicates the VMN as a relevant site for the antiobesity effects of oxytocin. oxytocin; ventromedial hypothalamus; energy expenditure; obesity; feeding OXYTOCIN HAS ANTIOBESITY EFFECTS and is currently being tested clinically for use in the treatment of obesity and Type 2 diabetes (34, 65). Although the mechanism for oxytocin's effects have not been fully characterized, an extensive body of work has demonstrated antiobesity effects of oxytocin in rodents (11,26,30,64,65), as well as humans (65). Behaviorally, central oxytocin has been reported to delay meal onset (2) and reduce intake of sweet foods (22,27,33). Additionally, previous studies implicate a physiological role for endogenous oxytocin in reducing meal size (7, 62). In addition to feeding effects, central oxytocin has potent effects on energy metabolism. For example, low doses of intracerebroventricular oxytocin promote weight loss in rats without affecting feeding by elevating fat oxidation in adipose tissue, whereas higher doses of intracerebroventricular oxytocin both reduce feeding and increase lipolysis (11). Conversely, animals deficient in either oxytocin or its receptor show reduced energy expenditure, in some cases with normal feeding (1, 9, 19, 51).The main sources of oxytocin in the brain are the magnocellular and par...

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Involvement of Prolactin‐Releasing Peptide in the Activation of Oxytocin Neurones in Response to Food Intake

Cited by 46 publications

References 70 publications

Translational and therapeutic potential of oxytocin as an anti-obesity strategy: Insights from rodents, nonhuman primates and humans

Translational and therapeutic potential of oxytocin as an anti-obesity strategy: Insights from rodents, nonhuman primates and humans

Supraoptic oxytocin and vasopressin neurons function as glucose and metabolic sensors

Oxytocin in the ventromedial hypothalamic nucleus reduces feeding and acutely increases energy expenditure

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