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Inflammation-induced anorexia and fever are elicited by distinct prostaglandin dependent mechanisms, whereas conditioned taste aversion is prostaglandin independent.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Region Östergötland, Närsjukvården i centrala Östergötland, Akutkliniken.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten.ORCID-id: 0000-0003-2245-3396
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten.
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2017 (Engelska)Ingår i: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 61, s. 236-243, artikel-id S0889-1591(16)30549-9Artikel i tidskrift (Refereegranskat) 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.

Ort, förlag, år, upplaga, sidor
Elsevier, 2017. Vol. 61, s. 236-243, artikel-id S0889-1591(16)30549-9
Nyckelord [en]
Anorexia, Conditioned place aversion, Cyclooxygenase, Fever, Inflammation, Lipopolysaccharide
Nationell ämneskategori
Immunologi inom det medicinska området
Identifikatorer
URN: urn:nbn:se:liu:diva-136127DOI: 10.1016/j.bbi.2016.12.007ISI: 000395365900026PubMedID: 27940259OAI: oai:DiVA.org:liu-136127DiVA, id: diva2:1085249
Anmärkning

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

Tillgänglig från: 2017-03-28 Skapad: 2017-03-28 Senast uppdaterad: 2018-05-02Bibliografiskt granskad
Ingår i avhandling
1. Mechanisms Behind Illness-Induced Anorexia
Öppna denna publikation i ny flik eller fönster >>Mechanisms Behind Illness-Induced Anorexia
2016 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
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.

Ort, förlag, år, upplaga, sidor
Linköping: Linköping University Electronic Press, 2016. s. 79
Serie
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1549
Nationell ämneskategori
Cell- och molekylärbiologi Neurovetenskaper
Identifikatorer
urn:nbn:se:liu:diva-132640 (URN)10.3384/diss.diva-132640 (DOI)9789176856482 (ISBN)
Disputation
2016-12-09, Berzeliussalen, Campus US, Linköping, 13:00 (Svenska)
Opponent
Handledare
Tillgänglig från: 2016-11-18 Skapad: 2016-11-18 Senast uppdaterad: 2019-10-29Bibliografiskt granskad

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Nilsson, AnnaWilhelms, DanielMirrasekhian, ElaheJaarola, MaaritBlomqvist, AndersEngblom, David
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