Differential roles of tumor necrosis factor-alpha and interferon-gamma in mouse hypermetabolic and anorectic responses induced by LPS

Details

Serval ID
serval:BIB_0AE76A060D5B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Differential roles of tumor necrosis factor-alpha and interferon-gamma in mouse hypermetabolic and anorectic responses induced by LPS
Journal
European Cytokine Network
Author(s)
Arsenijevic  D., Garcia  I., Vesin  C., Vesin  D., Arsenijevic  Y., Seydoux  J., Girardier  L., Ryffel  B., Dulloo  A., Richard  D.
ISSN
1148-5493 (Print)
Publication state
Published
Issued date
12/2000
Volume
11
Number
4
Pages
662-8
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Dec
Abstract
Lipopolysaccharide (LPS)-induced effects on energy balance are characterized by alterations in energy expenditure (hypermetabolism) and food intake (anorexia). To study the role of tumour necrosis factor alpha (TNF-alpha) on some of these metabolic responses to endotoxin, we have used transgenic mice expressing soluble tumour necrosis factor receptor-1 IgG fusion protein (TNFR1-IgG) as well as TNF-alpha knockout (KO), lymphotoxin-alpha (LT-alpha) KO, and interferon-gamma receptor (IFN-gamma R) KO mice. The results from TNFR1-IgG transgenic mice suggest that the hypermetabolic and anorectic responses induced by LPS are independently regulated since, in the absence of TNF-alpha or LT-alpha, the LPS-induced hypermetabolism is almost prevented but not the anorexia. The anorectic response shows the strongest association with IFN-gamma since both IFN-gamma R KO mice and mice treated with anti-IFN-gamma antibody showed marked reduction in the LPS-induced anorexia compared to other mice. IFN-gamma R KO mice also have an attenuated thermogenic response to endotoxin. Anti-Asialo GM1 antibody treatment attenuated both the hypermetabolic and anorectic responses to LPS, to an extent comparable to that observed in IFN-gamma R KO mice. This finding suggests that natural killer cells (lymphocytic subsets) may be involved in IFN-gamma production and play an important role in the metabolic alterations induced by LPS. We also showed that the hypermetabolic response of control mice is associated with an upregulation of cytokine expression within the brain and an increase in permeability of the blood brain barrier. LPS-induced anorexia appears to involve peripheral cytokine expression.
Keywords
Animals Antigens, CD/genetics Blood-Brain Barrier/drug effects Brain/anatomy & histology/drug effects/immunology Cytokines/biosynthesis/blood/genetics *Eating *Energy Metabolism/drug effects Evans Blue/metabolism Female Interferon Type II/biosynthesis/*immunology Lipopolysaccharides/*pharmacology Lymphotoxin-alpha/genetics/immunology Male Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic RNA, Messenger/biosynthesis Receptors, Interferon/genetics Receptors, Tumor Necrosis Factor/genetics Receptors, Tumor Necrosis Factor, Type I Spleen/drug effects/immunology Trans-Activation (Genetics) Tumor Necrosis Factor-alpha/biosynthesis/genetics/*immunology
Pubmed
Web of science
Create date
28/01/2008 12:31
Last modification date
20/08/2019 12:32
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