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; Tavernier, J

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 Tavernier, J

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Publication Type:: Journal Article
Citation:: Cellular and Molecular Life Sciences, 2015, 72 (3), pp. 629 - 644
Issue Date:: 2015-01-01

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Field	Value	Language
dc.contributor.author	Zabeau, L	en_US
dc.contributor.author	Jensen, CJ	en_US
dc.contributor.author	Seeuws, S	en_US
dc.contributor.author	Venken, K	en_US
dc.contributor.author	Verhee, A	en_US
dc.contributor.author	Catteeuw, D	en_US
dc.contributor.author	Van Loo, G	en_US
dc.contributor.author	Chen, H https://orcid.org/0000-0001-6883-3752	en_US
dc.contributor.author	Walder, K	en_US
dc.contributor.author	Hollis, J	en_US
dc.contributor.author	Foote, S	en_US
dc.contributor.author	Morris, MJ	en_US
dc.contributor.author	Van Der Heyden, J	en_US
dc.contributor.author	Peelman, F	en_US
dc.contributor.author	Oldfield, BJ	en_US
dc.contributor.author	Rubio, JP	en_US
dc.contributor.author	Elewaut, D	en_US
dc.contributor.author	Tavernier, J	en_US
dc.date.available	2014-07-28	en_US
dc.date.issued	2015-01-01	en_US
dc.identifier.citation	Cellular and Molecular Life Sciences, 2015, 72 (3), pp. 629 - 644	en_US
dc.identifier.issn	1420-682X	en_US
dc.identifier.uri	http://hdl.handle.net/10453/30584
dc.description.abstract	© 2014 The Author(s). 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.	en_US
dc.relation.ispartof	Cellular and Molecular Life Sciences	en_US
dc.relation.isbasedon	10.1007/s00018-014-1697-x	en_US
dc.subject.classification	Biochemistry & Molecular Biology	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Mice, Mutant Strains	en_US
dc.subject.mesh	Arthritis, Experimental	en_US
dc.subject.mesh	Encephalomyelitis, Autoimmune, Experimental	en_US
dc.subject.mesh	Leptin	en_US
dc.subject.mesh	DNA Primers	en_US
dc.subject.mesh	Blotting, Western	en_US
dc.subject.mesh	Flow Cytometry	en_US
dc.subject.mesh	Analysis of Variance	en_US
dc.subject.mesh	Reverse Transcriptase Polymerase Chain Reaction	en_US
dc.subject.mesh	Sequence Analysis, DNA	en_US
dc.subject.mesh	Sequence Deletion	en_US
dc.subject.mesh	Base Sequence	en_US
dc.subject.mesh	Protein Structure, Tertiary	en_US
dc.subject.mesh	Molecular Sequence Data	en_US
dc.subject.mesh	Male	en_US
dc.subject.mesh	Receptors, Leptin	en_US
dc.subject.mesh	HEK293 Cells	en_US
dc.subject.mesh	MCF-7 Cells	en_US
dc.subject.mesh	Myelin-Oligodendrocyte Glycoprotein	en_US
dc.subject.mesh	Chemical and Drug Induced Liver Injury	en_US
dc.title	Leptin's metabolic and immune functions can be uncoupled at the ligand/receptor interaction level	en_US
dc.type	Journal Article
utslib.citation.volume	3	en_US
utslib.citation.volume	72	en_US
utslib.for	0601 Biochemistry and Cell Biology	en_US
utslib.for	1103 Clinical Sciences	en_US
utslib.for	0606 Physiology	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	closed_access
pubs.issue	3	en_US
pubs.publication-status	Published	en_US
pubs.volume	72	en_US

Abstract:

© 2014 The Author(s). 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.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/30584