Oxytocin Receptor in the Hypothalamus Is Sufficient to Rescue Normal Thermoregulatory Function in Male Oxytocin Receptor Knockout Mice

Kasahara, Yoshiyuki; Sato, Keisuke; Takayanagi, Yuki; Mizukami, Hiroaki; Ozawa, Keiya; Hidema, Shizu; So, Kyoung Ha; Kawada, Teruo; Inoue, Nao; Ikeda, Ikuo; Roh, Sang Gun; Itoi, Keiichi; Nishimori, Katsuhiko

doi:10.1210/en.2012-2206

Cited by 83 publications

(89 citation statements)

References 54 publications

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“…In support of the former (that oxytocin in the VMN increases the thermic effect of food), it was reported that oxytocin in the DMH/VMN is essential for cold-induced thermogenesis (18). Oxytocin receptor-deficient mice have reduced ␤ 3 -adrenergic receptor expression and elevated expression of ␣ 2A -adrenergic receptor in brown adipocytes (18).…”

Section: Discussionmentioning

confidence: 96%

“…Oxytocin receptor-deficient mice have reduced ␤ 3 -adrenergic receptor expression and elevated expression of ␣ 2A -adrenergic receptor in brown adipocytes (18). ␤ 3 -adrenergic receptor and ␣ 2A -adrenergic receptor have opposing actions in brown adipose tissue, ␤ 3 -adrenergic receptor activation increases thermogenesis, whereas ␣ 2A -adrenergic receptor activation inhibits thermogenesis (for review, see Refs.…”

Section: Discussionmentioning

confidence: 99%

“…2) VMN lesions are associated with reduced sympathetic nervous system activity and delayed satiety leading to obesity (45,50,57). Similarly, the prominent characteristic of oxytocin deficiency in mice is reduced energy expenditure due to reduced sympathetic tone (9,18,51). 3) Peripheral injections of oxytocin sufficient to induce negative energy balance are associated with elevated c-Fos activation in both the VMN and NTS (64), suggesting that in addition to NTS, VMN may be an important site for oxytocin effects on energy balance.…”

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confidence: 99%

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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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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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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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“…In humans, oxytocin has been related to many social behaviors as in other mammals, but also more "abstract" sociality such as that found in economic trust games (Kosfeld et al, 2005;Zak et al, 2007). Recent studies have begun to reveal a direct link between OT and the other previously mentioned homeostatic processes, namely thermoregulation and metabolism (Kasahara et al, 2007(Kasahara et al, , 2013Takayanagi et al, 2008;Chaves et al, 2013). Chaves et al (2013) found support that OT has inhibitory effects on carbohydrate preferences and is associated with rectal temperatures.…”

Section: Moving To Exploration and Energeticsmentioning

confidence: 92%

Toward a Radically Embodied Neuroscience of Attachment and Relationships?

2014

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Attachment theory (Bowlby, 1969(Bowlby, /1982 posits the existence of internal working models as a foundational feature of human bonds. Radical embodied approaches instead suggest that cognition requires no computation or representation, favoring a cognition situated in a body in an environmental context with affordances for action (Chemero, 2009;Barrett, 2011;Wilson and Golonka, 2013;Casasanto and Lupyan, 2015). We explore whether embodied approaches to social soothing, interpersonal warmth, separation distress, and support seeking could replace representational constructs such as internal working models with a view of relationship cognition anchored in the resources afforded to the individual by their brain, body, and environment in interaction. We review the neurobiological bases for social attachments and relationships and attempt to delineate how these systems overlap or don't with more basic physiological systems in ways that support or contradict a radical embodied explanation. We suggest that many effects might be the result of the fact that relationship cognition depends on and emerges out of the action of neural systems that regulate several clearly physically grounded systems. For example, the neuropeptide oxytocin appears to be central to attachment and pair-bond behavior (Carter and Keverne, 2002) and is implicated in social thermoregulation more broadly, being necessary for maintaining a warm body temperature (for a review, see IJzerman et al., 2015b). Finally, we discuss the most challenging issues around taking a radically embodied perspective on social relationships. We find the most crucial challenge in individual differences in support seeking and responses to social contact, which have long been thought to be a function of representational structures in the mind (e.g., Baldwin, 1995). Together we entertain the thought to explain such individual differences without mediating representations or computations, but in the end propose a hybrid model of radical embodiment and internal representations.

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“…To our knowledge, gene expression of oxytocin receptor in the hypothalamus under the conditions of chronic stress in rats or mice has not been studied thus far. Oxytocin receptors in the hypothalamus play an important role in energy homeostasis, including feeding behavior (Arletti et al 1989) and thermoregulation (Kasahara et al 2013). Oxytocin receptors are located in several hypothalamic nuclei and their roles in reproductive functions are underlined by changes in binding and/or gene expression during the estrous cycle and pregnancy (Bale et al 1995, Bealer et al 2006.…”

Section: Discussionmentioning

confidence: 99%

Effects of atosiban on stress-related neuroendocrine factors

Babic¹,

Pokusa²,

Danevova³

et al. 2015

Journal of Endocrinology

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Atosiban, an oxytocin/vasopressin receptor antagonist, is used to decrease preterm uterine activity. The risk of preterm delivery is undoubtedly associated with stress, but potential side effects of atosiban on neuroendocrine functions and stress-related pathways are mostly unknown. These studies were designed to test the hypothesis that the chronic treatment of rats with atosiban modulates neuroendocrine functions under stress conditions. Male rats were treated (osmotic minipumps) with atosiban (600 mg/kg per day) or vehicle and were restrained for 120 min/day for 14 days. All animals were treated with a marker of cell proliferation 5-bromo-2-deoxyuridine. Anxiety-like behavior was measured using an elevated plus-maze. Treatment with atosiban failed to modify plasma concentrations of the stress hormones ACTH and corticosterone, but led to a rise in circulating copeptin. Atosiban increased prolactin levels in the non-stressed group. Oxytocin receptor mRNA levels were increased in rats exposed to stress. Treatment with atosiban, in both control and stressed animals, resulted in a decrease in oxytocin receptor gene expression in the hypothalamus. No changes were observed in vasopressin receptor 1A and 1B gene expression. The decrease in hippocampal cell proliferation induced by stress exposure was not modified by atosiban treatment. This study provides the first data, to our knowledge, revealing the effect of atosiban on gene expression of oxytocin receptors in the brain. Atosiban-induced enhancement of plasma copeptin indicates an elevation in vasopressinergic tone with potential influence on water-electrolyte balance.

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Oxytocin Receptor in the Hypothalamus Is Sufficient to Rescue Normal Thermoregulatory Function in Male Oxytocin Receptor Knockout Mice

Cited by 83 publications

References 54 publications

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

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

Toward a Radically Embodied Neuroscience of Attachment and Relationships?

Effects of atosiban on stress-related neuroendocrine factors

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