Leptin’s metabolic and immune functions can be uncoupled at the ligand/receptor interaction level
| Autor: | Simon J. Foote, Jacob Harvey Hollis, Dominiek Catteeuw, Koen Venken, Geert van Loo, Margaret J. Morris, Justin P. Rubio, Hui Chen, Dirk Elewaut, Annick Verhee, Cathy J Jensen, Jan Tavernier, Ken Walder, José Van der Heyden, Brian J. Oldfield, Frank Peelman, Sylvie Seeuws, Lennart Zabeau |
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| Jazyk: | angličtina |
| Předmět: |
Leptin
Male medicine.medical_treatment Genetic model AUTOIMMUNE ENCEPHALOMYELITIS PROTECTS MICE Immunoglobulin D ACTIVATION Mice Autoimmune disease Receptor MUTATION Sequence Deletion Reverse Transcriptase Polymerase Chain Reaction Flow Cytometry 3. Good health Leptin receptor DB/DB MICE DEFICIENCY Cytokine MCF-7 Cells Receptors Leptin Molecular Medicine Chemical and Drug Induced Liver Injury Research Article Biochemistry & Molecular Biology medicine.medical_specialty Encephalomyelitis Autoimmune Experimental Blotting Western Molecular Sequence Data Biology OB/OB MICE Cellular and Molecular Neuroscience Immune system Internal medicine medicine OB-R Animals Humans Obesity Molecular Biology DNA Primers Pharmacology Analysis of Variance Base Sequence RECEPTOR Antagonist Biology and Life Sciences Sequence Analysis DNA Cell Biology JANUS KINASE/SIGNAL TRANSDUCER medicine.disease Arthritis Experimental Mice Mutant Strains Protein Structure Tertiary Endocrinology HEK293 Cells Metabolism biology.protein Nanobody Myelin-Oligodendrocyte Glycoprotein |
| Zdroj: | CELLULAR AND MOLECULAR LIFE SCIENCES Cellular and Molecular Life Sciences |
| ISSN: | 1420-682X |
| DOI: | 10.1007/s00018-014-1697-x |
| Popis: | 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. Electronic supplementary material The online version of this article (doi:10.1007/s00018-014-1697-x) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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