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Leptin's metabolic and immune functions can be uncoupled at the ligand/receptor interaction level.

Zabeau,L, Jensen,CJ, Seeuws,S, Venken,K, Verhee,A, Catteeuw,D, van Loo,G, Chen,H, Walder,K, Hollis,J, Foote,S, Morris,MJ, Van der Heyden,J, Peelman,F, Oldfield,BJ, Rubio,JP, Elewaut,D and Tavernier,J 2015, Leptin's metabolic and immune functions can be uncoupled at the ligand/receptor interaction level., Cellular and Molecular Life Sciences, vol. 72, no. 3, pp. 629-644, doi: 10.1007/s00018-014-1697-x.

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Title Leptin's metabolic and immune functions can be uncoupled at the ligand/receptor interaction level.
Author(s) Zabeau,L
Jensen,CJ
Seeuws,S
Venken,K
Verhee,A
Catteeuw,D
van Loo,G
Chen,H
Walder,K
Hollis,J
Foote,S
Morris,MJ
Van der Heyden,J
Peelman,F
Oldfield,BJ
Rubio,JP
Elewaut,D
Tavernier,J
Journal name Cellular and Molecular Life Sciences
Volume number 72
Issue number 3
Start page 629
End page 644
Publisher Springer Verlag
Place of publication Switzerland
Publication date 2015-02
ISSN 1420-9071
Keyword(s) Antagonist
Autoimmune disease
Genetic model
Leptin receptor
Metabolism
Nanobody
Obesity
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Cell Biology
JANUS KINASE/SIGNAL TRANSDUCER
DB/DB MICE
OB/OB MICE
AUTOIMMUNE ENCEPHALOMYELITIS
PROTECTS MICE
OB-R
RECEPTOR
DEFICIENCY
ACTIVATION
MUTATION
Summary The adipocyte-derived cytokine leptin acts as a metabolic switch, connecting the body's metabolism to high-energy consuming processes such as reproduction and immune responses. We here provide genetic and biochemical evidence that the metabolic and immune functions of leptin can be uncoupled at the receptor level. First, homozygous mutant fatt/fatt mice carry a spontaneous splice mutation causing deletion of the leptin receptor (LR) immunoglobulin-like domain (IGD) in all LR isoforms. These mice are hyperphagic and morbidly obese, but display only minimal changes in size and cellularity of the thymus, and cellular immune responses are unaffected. These animals also displayed liver damage in response to concavalin A comparable to wild-type and heterozygous littermates. Second, treatment of healthy mice with a neutralizing nanobody targeting IGD induced weight gain and hyperinsulinaemia, but completely failed to block development of experimentally induced autoimmune diseases. These data indicate that leptin receptor deficiency or antagonism profoundly affects metabolism, with little concomitant effects on immune functions.
Language eng
DOI 10.1007/s00018-014-1697-x
Field of Research 110799 Immunology not elsewhere classified
Socio Economic Objective 929999 Health not elsewhere classified
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2015, Springer Verlag
Persistent URL http://hdl.handle.net/10536/DRO/DU:30070243

Document type: Journal Article
Collection: School of Medicine
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