Oxytocin receptor-deficient mice developed late-onset obesity

Takayanagi, Yuki; Kasahara, Yoshiyuki; Onaka, Tatsushi; Takahashi, Nobuyuki; Kawada, Teruo; Nishimori, Katsuhiko

doi:10.1097/wnr.0b013e3283021ca9

Cited by 249 publications

(257 citation statements)

References 26 publications

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“…Genetic perturbations of either oxytocin and its receptor or PGC-1␣ lead to similar abnormalities in the regulation of body weight and metabolism: Both PGC-1␣ Ϫ/Ϫ and oxytocin receptor-deficient mice exhibit impaired thermoregulation and develop late-onset obesity (Wu et al, 1999;Lin et al, 2004;Leone et al, 2005;Takayanagi et al, 2008). Defects in oxytocin secretion were found to affect food intake and cause anorexia (Maejima et al, 2009;Zhang et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

The Metabolic Regulator PGC-1α Directly Controls the Expression of the Hypothalamic Neuropeptide Oxytocin

Blechman¹,

Amir-Zilberstein²,

Gutnick³

et al. 2011

J. Neurosci.

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The transcriptional coactivator PGC-1␣ is a key regulator of cellular energy expenditure in peripheral tissues. Recent studies report that PGC-1␣-null mice develop late-onset obesity and that the neuronal inactivation of PGC-1␣ causes increased food intake. However, the exact role of PGC-1␣ in the CNS remains unclear. Here we show that PGC-1␣ directly regulates the expression of the hypothalamic neuropeptide oxytocin, a known central regulator of appetite. We developed a unique genetic approach in the zebrafish, allowing us to monitor and manipulate PGC-1␣ activity in oxytocinergic neurons. We found that PGC-1␣ is coexpressed with oxytocin in the zebrafish hypothalamus. Targeted knockdown of the zebrafish PGC-1␣ gene activity caused a marked decrease in oxytocin mRNA levels and inhibited the expression of a transgenic GFP reporter driven by the oxytocin promoter. The effect of PGC-1␣ loss of function on oxytocin gene activity was rescued by tissue-specific re-expression of either PGC-1␣ or oxytocin precursor in zebrafish oxytocinergic neurons. PGC-1␣ activated the oxytocin promoter in a heterologous cell culture system, and overexpression of PGC-1␣ induced ectopic expression of oxytocin in muscles and neurons. Finally, PGC-1␣ forms an in vivo complex with the oxytocin promoter in fed but not fasted animals. These findings demonstrate that PGC-1␣ is both necessary and sufficient for the production of oxytocin, implicating hypothalamic PGC-1␣ in the direct activation of a hypothalamic hormone known to control energy intake.

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Section: Introductionmentioning

confidence: 99%

The Metabolic Regulator PGC-1α Directly Controls the Expression of the Hypothalamic Neuropeptide Oxytocin

Blechman¹,

Amir-Zilberstein²,

Gutnick³

et al. 2011

J. Neurosci.

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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: 91%

Toward a Radically Embodied Neuroscience of Attachment and Relationships?

Beckes¹,

IJzerman²

2017

Preprint

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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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“…Mice lacking oxytocin or oxytocin receptors develop late-onset obesity with little changes in daily food intake [351][352][353], and pair-feeding studies confirm that reductions in eating only partially account for oxytocin's effect on body weight, suggesting that oxytocin also controls energy expenditure [354,355].…”

Section: Oxytocinmentioning

confidence: 94%

Neuroendocrine control of satiation

Asarian¹,

Bächler

2014

Hormone Molecular Biology and Clinical Investigation

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Abstract:Eating is a simple behavior with complex functions. The unconscious neuroendocrine process that stops eating and brings a meal to its end is called satiation. Energy homeostasis is mediated accomplished through the control of meal size via satiation. It involves neural integrations of phasic negative-feedback signals related to ingested food and tonic signals, such as those related to adipose tissue mass. Energy homeostasis is accomplished through adjustments in meal size brought about by changes in these satiation signals. The best understood meal-derived satiation signals arise from gastrointestinal nutrient sensing. Gastrointestinal hormones secreted during the meal, including cholecystokinin, glucagon-like peptide 1, and PYY, mediate most of these. Other physiological signals arise from activation of metabolic-sensing neurons, mainly in the hypothalamus and caudal brainstem. We review both classes of satiation signal and their integration in the brain, including their processing by melanocortin, neuropeptide Y/agouti-related peptide, serotonin, noradrenaline, and oxytocin neurons. Our review is not comprehensive; rather, we discuss only what we consider the best-understood mechanisms of satiation, with a special focus on normally operating physiological mechanisms.

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Oxytocin receptor-deficient mice developed late-onset obesity

Cited by 249 publications

References 26 publications

The Metabolic Regulator PGC-1α Directly Controls the Expression of the Hypothalamic Neuropeptide Oxytocin

The Metabolic Regulator PGC-1α Directly Controls the Expression of the Hypothalamic Neuropeptide Oxytocin

Toward a Radically Embodied Neuroscience of Attachment and Relationships?

Neuroendocrine control of satiation

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