Endothelial cell leptin receptor mutant mice have hyperleptinemia and reduced tissue uptake
Autor: | Yuping Wang, Bhavaani Jayaram, Weihong Pan, Hung Hsuchou, Abba J. Kastin, Suidong Ouyang |
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Rok vydání: | 2013 |
Předmět: |
Leptin
medicine.medical_specialty Physiology Clinical Biochemistry Serum albumin Biological Transport Active Adipose tissue Kidney Article Excretion Mice Internal medicine medicine Animals Tissue Distribution Obesity RNA Messenger Serum Albumin Mice Knockout Leptin receptor biology Protein Stability digestive oral and skin physiology Brain Endothelial Cells Cell Biology Endothelial stem cell medicine.anatomical_structure Endocrinology Adipose Tissue Renal physiology biology.protein Receptors Leptin hormones hormone substitutes and hormone antagonists |
Zdroj: | Journal of Cellular Physiology. 228:1610-1616 |
ISSN: | 0021-9541 |
Popis: | Hyperleptinemia is usually associated with obesity and leptin resistance. Endothelial cell leptin receptor knockout (ELKO) mice without a signaling membrane-bound leptin receptor in endothelia, however, have profound hyperleptinemia without signs of leptin resistance. Leptin mRNA in adipose tissue was unchanged. To test the hypothesis that the ELKO mutation results in delayed degradation and slowed excretion, we determined the kinetics of leptin transfer in groups of ELKO and wildtype mice after intravenous bolus injection of 125I-leptin and the reference substance 131I-albumin. The degradation pattern of 125I-leptin in serum and brain homogenates at different time points between 10 and 60 min was measured by HPLC and acid precipitation. Although ELKO mice had reduced uptake of 125I-leptin uptake by the brain and several peripheral organs, leptin was more stable in blood and tissue. There was no change in the rate of renal excretion. ELISA showed that serum soluble leptin receptor, known to antagonize leptin transport, had a 400-fold increase, probably contributing to the hyperleptinemia and reduced tissue uptake. Thus, the ELKO mutation unexpectedly increased the stability of leptin but suppressed its tissue uptake. These changes probably contribute to the known partial resistance of the ELKO mice to diet-induced obesity. J. Cell. Physiol. 228: 1610–1616, 2013. © 2013 Wiley Periodicals, Inc. |
Databáze: | OpenAIRE |
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