title: The soluble leptin receptor.
abstract: The adipokine leptin realizes signal transduction via four different leptin receptor (OB-R) isoforms. The amount of functionally active OB-R, however, is affected by constitutive shedding of the extracellular domain. The product of the cleavage process, the so-called soluble leptin receptor (sOB-R), is the main binding protein for leptin in human blood and modulates its bioavailability. Concentrations of sOB-R are differentially regulated in metabolic disorders, such as type 1 diabetes mellitus or obesity, and can, therefore, enhance or reduce leptin sensitivity. Lipotoxicity and apoptosis increase OB-R cleavage via ADAM10-dependent mechanisms. In contrast, although increased sOB-R concentrations seem to directly inhibit leptin effects, reduced amounts of sOB-R may reflect decreased membrane expression of OB-R. These findings, in part, explain alterations of leptin sensitivity that are associated with changes in serum sOB-R concentrations seen in metabolic disorders.
authors.affiliation: Institute of Laboratory Medicine Clinical Chemistry and Molecular Diagnostics, Leipzig, Germany. Electronic address: michael.schaab@medizin.uni-leipzig.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Schaab
authors.affiliation: Institute of Laboratory Medicine Clinical Chemistry and Molecular Diagnostics, Leipzig, Germany.
authors.forename: Juergen
authors.initials: J
authors.lastname: Kratzsch
mesh_terms: D000072197:ADAM10 Protein / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D006801:Humans; D020738:Leptin / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D054411:Receptors, Leptin / Q000378:metabolism*
chemical_list: D020738:Leptin; D054411:Receptors, Leptin; D000072197:ADAM10 Protein
keywords: ADAM protease; diabetes; leptin receptor; leptin resistance; obesity; shedding