liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • 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
Inflammation-induced anorexia and fever are elicited by distinct prostaglandin dependent mechanisms, whereas conditioned taste aversion is prostaglandin independent.
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.ORCID iD: 0000-0003-2245-3396
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
Show others and affiliations
2017 (English)In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 61, 236-243 p., S0889-1591(16)30549-9Article in journal (Refereed) Published
Abstract [en]

Systemic inflammation evokes an array of brain-mediated responses including fever, anorexia and taste aversion. Both fever and anorexia are prostaglandin dependent but it has been unclear if the cell-type that synthesizes the critical prostaglandins is the same. Here we show that pharmacological inhibition or genetic deletion of cyclooxygenase (COX)-2, but not of COX-1, attenuates inflammation-induced anorexia. Mice with deletions of COX-2 selectively in brain endothelial cells displayed attenuated fever, as demonstrated previously, but intact anorexia in response to peripherally injected lipopolysaccharide (10μg/kg). Whereas intracerebroventricular injection of a cyclooxygenase inhibitor markedly reduced anorexia, deletion of COX-2 selectively in neural cells, in myeloid cells or in both brain endothelial and neural cells had no effect on LPS-induced anorexia. In addition, COX-2 in myeloid and neural cells was dispensable for the fever response. Inflammation-induced conditioned taste aversion did not involve prostaglandin signaling at all. These findings collectively show that anorexia, fever and taste aversion are triggered by distinct routes of immune-to-brain signaling.

Place, publisher, year, edition, pages
Elsevier, 2017. Vol. 61, 236-243 p., S0889-1591(16)30549-9
Keyword [en]
Anorexia, Conditioned place aversion, Cyclooxygenase, Fever, Inflammation, Lipopolysaccharide
National Category
Immunology in the medical area
Identifiers
URN: urn:nbn:se:liu:diva-136127DOI: 10.1016/j.bbi.2016.12.007ISI: 000395365900026PubMedID: 27940259OAI: oai:DiVA.org:liu-136127DiVA: diva2:1085249
Note

Funding agencies: Swedish Medical Research Council [20725, 07879]; European Research Council; Knut and Alice Wallenberg foundation; Swedish Brain Foundation; Swedish Cancer Foundation [213/692]; County Council of Ostergotland

Available from: 2017-03-28 Created: 2017-03-28 Last updated: 2017-06-14Bibliographically approved
In thesis
1. Mechanisms Behind Illness-Induced Anorexia
Open this publication in new window or tab >>Mechanisms Behind Illness-Induced Anorexia
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Loss of appetite is together with fever and malaise hallmarks of infection. Loosing appetite during an acute infection such as influenza does not result in any longlasting effects, but loosing appetite during chronic diseases such as cancer or AIDS constitutes a risk factor for mortality. Food intake regulation during inflammation is orchestrated by the brain in response to peripheral inflammatory signals. It is known that expression of the prostaglandin synthesizing enzyme cyclooxygenase 2 (COX-2) is crucial for the mechanisms underlying inflammation-induced anorexia, and that prostaglandin E2 (PGE2) is involved in anorexia induced by interleukin-1 beta (IL-1β). In this thesis I examined the prostaglandin-pathways proposed to be involved in anorexia. We show that acute anorexia is dependent on COX-2 expression, while cancer-induced anorexia is mediated by cyclooxygenase 1 (COX-1), at least in the initial stages, suggesting that the signaling pathways for chronic- and acute anorexia are distinct. We were able to demonstrate that the pathway underlying acute anorexia is distinct from that of fever, and that taste aversion is prostaglandin independent. We could also show that both acute and chronic anorexia-cachexia is dependent on expression of myeloid differentiation primary response gene (MyD88) in hematopoietic/myeloid cells.

In summary, the findings presented in this thesis suggest that anorexia is a result of many different signaling pathways, as opposed to what is the case for several other inflammatory symptoms such as fever and malaise, where the pathways have been shown to be very exclusive. This provides new insight into the diversity of the pathways underlying inflammatory symptoms, which is fundamental for the ability to present potential, symptom-specific drug targets.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2016. 79 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1549
National Category
Cell and Molecular Biology Neurosciences
Identifiers
urn:nbn:se:liu:diva-132640 (URN)10.3384/diss.diva-132640 (DOI)9789176856482 (ISBN)
Public defence
2016-12-09, Berzeliussalen, Campus US, Linköping, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2016-11-18 Created: 2016-11-18 Last updated: 2017-06-14Bibliographically approved

Open Access in DiVA

fulltext(1163 kB)21 downloads
File information
File name FULLTEXT01.pdfFile size 1163 kBChecksum SHA-512
110e989947249821093a219bf5ab8e68a00c9cfeb6bb1412c9832d4f517280a5788b20e9950d95361abc51d062ba7bece17505529b499799a2c48bbe15c63d25
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Nilsson, AnnaWilhelms, DanielMirrasekhian, ElaheJaarola, MaaritBlomqvist, AndersEngblom, David
By organisation
Division of Cell BiologyFaculty of Medicine and Health SciencesDivision of Drug ResearchDepartment of Emergency Medicine
In the same journal
Brain, behavior, and immunity
Immunology in the medical area

Search outside of DiVA

GoogleGoogle Scholar
Total: 21 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 72 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • 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