Journal article

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

Lennart Zabeau, Cathy J Jensen, Sylvie Seeuws, Koen Venken, Annick Verhee, Dominiek Catteeuw, Geert van Loo, Hui Chen, Ken Walder, Jacob Hollis, Simon Foote, Margaret J Morris, Jose Van der Heyden, Frank Peelman, Brian J Oldfield, Justin P Rubio, Dirk Elewaut, Jan Tavernier



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 ..

View full abstract


Awarded by Fonds voor Wetenschappelijk Onderzoek-Vlaanderen

Awarded by Interuniversity Attraction Poles

Awarded by National Health and Medical Research Council of Australia (NHMRC)

Awarded by NHMRC

Awarded by ERC

Funding Acknowledgements

This work was supported by grants from the Fonds voor Wetenschappelijk Onderzoek-Vlaanderen (FWO-G.0864.10), the Interuniversity Attraction Poles (Grant P6:28), the Group-ID MRP of Ghent University and a National Health and Medical Research Council of Australia (NHMRC) Project Grant (257518). L.Z. and S.S. were supported by the FWO and by the Instituut voor Innovatie door Wetenschap en Technologie (IWT), respectively. J.P.R. was supported by an NHMRC Biomedical Career Development Award (323516) (NHMRC). B.J.O, M.J.M, S.J.F are fellows of the NHMRC, and JT is recipient of an ERC Advanced Grant 340941.