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Peripherally restri...
Peripherally restricted oxytocin is sufficient to reduce food intake and motivation, while CNS entry is required for locomotor and taste avoidance effects
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- Asker, Mohammed (författare)
- Gothenburg University,Göteborgs universitet,Wallenberg Centre for Molecular and Translational Medicine,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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- Krieger, Jean-Philippe (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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Liles, A. (författare)
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Tinsley, I. C. (författare)
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Borner, T. (författare)
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- Maric, Ivana (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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Doebley, S. (författare)
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Furst, C. D. (författare)
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- Börchers, Stina (författare)
- Gothenburg University,Göteborgs universitet,Wallenberg Centre for Molecular and Translational Medicine,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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- Longo, Francesco (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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Bhat, Y. R. (författare)
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De Jonghe, B. C. (författare)
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Hayes, M. R. (författare)
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Doyle, R. P. (författare)
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- Skibicka, Karolina P (författare)
- Gothenburg University,Göteborgs universitet,Wallenberg Centre for Molecular and Translational Medicine,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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(creator_code:org_t)
- 2023-01-09
- 2023
- Engelska.
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Ingår i: Diabetes Obesity & Metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 25:3, s. 856-877
- Relaterad länk:
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- ObjectivesOxytocin (OT) has a well-established role in reproductive behaviours; however, it recently emerged as an important regulator of energy homeostasis. In addition to central nervous system (CNS), OT is found in the plasma and OT receptors (OT-R) are found in peripheral tissues relevant to energy balance regulation. Here, we aim to determine whether peripheral OT-R activation is sufficient to alter energy intake and expenditure.Methods and ResultsWe first show that systemic OT potently reduced food intake and food-motivated behaviour for a high-fat reward in male and female rats. As it is plausible that peripherally, intraperitoneally (IP) injected OT crosses the blood-brain barrier (BBB) to produce some of the metabolic effects within the CNS, we screened, with a novel fluorescently labelled-OT (fAF546-OT, Roxy), for the presence of IP-injected Roxy in CNS tissue relevant to feeding control and compared such with BBB-impermeable fluorescent OT-B-12 (fCy5-OT-B-12; BRoxy). While Roxy did penetrate the CNS, BRoxy did not. To evaluate the behavioural and thermoregulatory impact of exclusive activation of peripheral OT-R, we generated a novel BBB-impermeable OT (OT-B-12), with equipotent binding at OT-R in vitro. In vivo, IP-injected OT and OT-B-12 were equipotent at food intake suppression in rats of both sexes, suggesting that peripheral OT acts on peripheral OT-R to reduce feeding behaviour. Importantly, OT induced a potent conditioned taste avoidance, indistinguishable from that induced by LiCl, when applied peripherally. Remarkably, and in contrast to OT, OT-B-12 did not induce any conditioned taste avoidance. Limiting the CNS entry of OT also resulted in a dose-dependent reduction of emesis in male shrews. While both OT and OT-B-12 proved to have similar effects on body temperature, only OT resulted in home-cage locomotor depression.ConclusionsTogether our data indicate that limiting systemic OT CNS penetrance preserves the anorexic effects of the peptide and reduces the clinically undesired side effects of OT: emesis, taste avoidance and locomotor depression. Thus, therapeutic targeting of peripheral OT-R may be a viable strategy to achieve appetite suppression with better patient outcomes.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Nyckelord
- food-motivated behaviour
- ingestive behaviour
- nausea
- peripheral
- oxytocin
- thermoregulation
- messenger-rna expression
- brown adipose-tissue
- methamphetamine-seeking
- postpartum hemorrhage
- nucleus-accumbens
- body-weight
- behavior
- receptors
- carbetocin
- anxiety
- Endocrinology & Metabolism
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
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Asker, Mohammed
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Krieger, Jean-Ph ...
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Liles, A.
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Tinsley, I. C.
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Borner, T.
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Maric, Ivana
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visa fler...
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Doebley, S.
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Furst, C. D.
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Börchers, Stina
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Longo, Francesco
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Bhat, Y. R.
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De Jonghe, B. C.
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Hayes, M. R.
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Doyle, R. P.
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Skibicka, Karoli ...
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Endokrinologi oc ...
- Artiklar i publikationen
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Diabetes Obesity ...
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Göteborgs universitet