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


Zabeau, L and Jensen, CJ and Seeuws, S and Venken, K and Verhee, A and Catteeuw, D and Van Loo, G and Chen, H and Walder, K and Hollis, J and Foote, S and Morris, MJ and Van Der Heyden, J and Peelman, F and Oldfield, BJ and Rubio, JP and Elewaut, D and Tavernier, J, Leptin's metabolic and immune functions can be uncoupled at the ligand/receptor interaction level, Cellular and Molecular Life Sciences, 72, (3) pp. 629-644. ISSN 1420-682X (2015) [Refereed Article]

Copyright Statement

Copyright 2014 The Authors

DOI: doi:10.1007/s00018-014-1697-x


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.

Item Details

Item Type:Refereed Article
Keywords:leptin receptor, antagonist, genetic model, nanobody, obesity, metabolism, autoimmune disease
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Cellular nervous system
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Foote, S (Professor Simon Foote)
ID Code:103036
Year Published:2015
Web of Science® Times Cited:10
Deposited By:Menzies Institute for Medical Research
Deposited On:2015-09-16
Last Modified:2017-11-03

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