The soluble leptin receptor
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- 作者：Michael Schaab ; PhD ; michael.schaab@medizin.uni-leipzig.de" class="auth_mail" title="E-mail the corresponding author ; Juergen Kratzsch ; PhD
- 关键词：leptin receptor ; leptin resistance ; obesity ; diabetes ; shedding ; ADAM protease
- 刊名：Best Practice Research Clinical Endocrinology Metabolism
- 出版年：2015
- 出版时间：October 2015
- 年：2015
- 卷：29
- 期：5
- 页码：661-670
- 全文大小：581 K
文摘
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.