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Molecular, Immunohistochemical, and Pharmacological Evidence of Oxytocin's Role as Inhibitor of Carbohydrate But Not Fat Intake
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
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2010 (English)In: Endocrinology, ISSN 0013-7227, E-ISSN 1945-7170, Vol. 151, no 10, 4736-4744 p.Article in journal (Refereed) Published
Abstract [en]

Oxytocin (OT) facilitates feeding termination stemming from high osmolality, stomach distention, and malaise. Recent knockout (KO) studies suggested a crucial function for OT in carbohydrate intake: OT-/- mice had increased preference for carbohydrates, including sucrose, but not fat (Intralipid). In striking contrast, sugar appetite was unaffected in the OT receptor KO mouse; data from wild-type animals have been insufficient. Therefore, we examined the involvement of OT in the regulation of sucrose vs. fat intake in C57BL/6 mice that served as a background KO strain. We exposed mice to a meal of sucrose or Intralipid and determined that the percentage of c-Fos-immunoreactive paraventricular hypothalamic OT neurons was elevated at termination of intake of either of the tastants, but this increase was 2-fold higher in sucrose-fed mice. A 48-h exposure to sucrose compared with Intralipid caused up-regulation of OT mRNA, whereas inherent individual preferences for sucrose vs. fat were not associated with differences in baseline OT expression as established with quantitative PCR. We found that L-368,899, an OT receptor antagonist, increased sugar intake when sucrose was presented alone or concurrently with Intralipid; it had no effect on Intralipid or total calorie consumption. L-368,899 affected Fos immunoreactivity in the paraventricular hypothalamus, arcuate nucleus, amygdala, and nucleus of the solitary tract, areas involved in aversion, satiety, and reward. This pattern serves as neuroanatomical basis of OT's complex role in food intake, including sucrose intake. The current findings expand our knowledge on OT and suggest that it acts as a carbohydrate-specific inhibitor of feeding. (Endocrinology 151: 4736-4744, 2010)

Place, publisher, year, edition, pages
2010. Vol. 151, no 10, 4736-4744 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-134798DOI: 10.1210/en.2010-0151ISI: 000282005700016OAI: oai:DiVA.org:uu-134798DiVA: diva2:373824
Available from: 2010-12-01 Created: 2010-12-01 Last updated: 2014-06-30Bibliographically approved
In thesis
1. Non-caloric regulation of food intake
Open this publication in new window or tab >>Non-caloric regulation of food intake
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Food intake is shaped by environmental, endocrine, metabolic, and reward-related signals. A change in appetite is an outcome of integration of the relevant external and internal stimuli. While the main purpose of eating is to reverse a negative energy balance, mechanisms protecting homeostasis change appetite for other reasons. This thesis examines the role of select brain mechanisms in regulating consumption driven by aspects other than energy.

In paper I, an increased percentage of c-Fos positive OT neurons was observed after mice ingested sucrose, while no change was found after Intralipid intake. Given a choice between isocaloric sugar and Intralipid solutions, mice injected with an OT receptor antagonist increase their preference for sucrose, while total calorie intake remains unchanged, suggesting that OT prevents overconsumption of sugar.

Paper II addresses whether MCH, which has anxiolytic properties and mediates reward-motivated feeding, has the ability to alleviate conditioned taste aversion in rats. We found that while mRNA expression of MCH and its receptor are changed in aversive animals, central injections of MCH do not prevent the acquisition of aversion, nor do they affect the rate of extinction of the taste aversion.

Paper III describes evidence that the N/OFQ system facilitates food intake by alleviating aversive responsiveness. Blocking the NOP receptor delays extinction of aversion and reduces food intake in hungry rats.

Paper IV reports that leucine ingestion increases mRNA expression levels of genes known to mediate reward, as well as orexigenic gene expression in the nucleus accumbens (Nacc), a key component of the reward circuit. Adding leucine to drinking water increases activity of the reward system, which possibly contributes to the pleasure of consumption.

A separate approach using Drosophila melanogaster is introduced in paper V which provides evidence that knocking down the gene for the transcription factor Ets96B during development results in a simultaneous disruption in sleep patterns and appetite, thus highlighting the interplay between these physiological parameters.

We conclude that OT, MCH, N/OFQ and Ets96B belong to mechanisms regulating food intake for reasons other than energy balance. Composition of food and negative associations with diets affect neural networks controlling appetite.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2014. 54 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1007
National Category
Research subject
urn:nbn:se:uu:diva-223809 (URN)978-91-554-8966-3 (ISBN)
Public defence
2014-06-13, B:21, BMC, Husargatan 3, Uppsala, 09:15 (English)
Available from: 2014-05-23 Created: 2014-04-25 Last updated: 2014-06-30

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