uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Leucine changes reward-related gene expression and neuronal activity in the hypothalamus and nucleus accumbens
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
Show others and affiliations
(English)Manuscript (preprint) (Other academic)
Abstract [en]

The branched-chain amino acid leucine has been shown to have satiating effects when administered centrally. However, studies on how oral administration of leucine affects appetite shown disparate effects ranging from orexigenic to anorexigenic. To shed more light on the effects of ingested leucine on the components of the forebrain circuitry  that govern feeding for hunger versus reward, we studied changes in c-Fos immunoreactivity (IR) immediately after 2-h 1.5 w/v % leucine vs water exposure and used qPCR to analyze relevant feeding-related gene transcripts in mice consuming leucine for 48 h.Leucine caused an increase in c-Fos IR in the arcuate nucleus and a decrease in the paraventricular nucleus whereas a trend towards an increase was detected in the nucleus accumbens shell. We found an increased expression of the µ-opioid receptor (MOR) in the Acb and δ-opioid receptor mRNA in the hypothalamus. Furthermore, expression of anorexigenic genes cocaine- and amphetamine-regulated transcript (CART), oxytocin (OXY) and arginine vasopressin (AVP) was downregulated in the Acb, and CRH expression was elevated in the hypothalamus of mice fed with leucine. Our results indicate that ingested leucine affects both the hunger- and reward-related circuits, which likely underlies the mixed orexigenic and anorexigenic outcomes of this amino acid’s consumption.

National Category
Neurosciences
Research subject
Medical Science
Identifiers
URN: urn:nbn:se:uu:diva-223807OAI: oai:DiVA.org:uu-223807DiVA: diva2:714276
Available from: 2014-04-25 Created: 2014-04-25 Last updated: 2014-06-30
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.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1007
National Category
Neurosciences
Research subject
Neuroscience
Identifiers
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)
Opponent
Supervisors
Available from: 2014-05-23 Created: 2014-04-25 Last updated: 2014-06-30

Open Access in DiVA

No full text

By organisation
Department of Neuroscience
Neurosciences

Search outside of DiVA

GoogleGoogle Scholar

urn-nbn

Altmetric score

urn-nbn
Total: 665 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf