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Tracking adiponectin biodistribution via fluorescence molecular tomography indicates increased vascular permeability after streptozotocin-induced diabetes
- Source :
- Am J Physiol Endocrinol Metab
- Publication Year :
- 2019
- Publisher :
- American Physiological Society, 2019.
-
Abstract
- Adiponectin, a highly abundant polypeptide hormone in plasma, plays an important role in the regulation of energy metabolism in a wide variety of tissues, as well as providing important beneficial effects in diabetes, inflammation, and cardiovascular disease. To act on target tissues, adiponectin must move from the circulation to the interstitial space, suggesting that vascular permeability plays an important role in regulating adiponectin action. To test this hypothesis, fluorescently labeled adiponectin was used to monitor its biodistribution in mice with streptozotocin-induced diabetes (STZD). Adiponectin was, indeed, found to have increased sequestration in the highly fenestrated liver and other tissues within 90 min in STZD mice. In addition, increased myocardial adiponectin was detected and confirmed using computed tomography (CT) coregistration. This provided support of adiponectin delivery to affected cardiac tissue as a cardioprotective mechanism. Higher adiponectin content in the STZD heart tissues was further examined by ex vivo fluorescence molecular tomography (FMT) imaging, immunohistochemistry, and Western blot analysis. In vitro mechanistic studies using an endothelial monolayer on inserts and three-dimensional microvascular networks on microfluidic chips further confirmed that adiponectin flux was increased by high glucose. However, in the in vitro model and mouse heart tissue, high glucose levels did not change adiponectin receptor levels. An examination of the tight junction (TJ) complex revealed a decrease in the TJ protein claudin (CLDN)-7 in high glucose-treated endothelial cells, and the functional significance of this change was underscored by increased endothelium permeability upon siRNA-mediated knockdown of CLDN-7. Our data support the idea that glucose-induced effects on permeability of the vascular endothelium contribute to the actions of adiponectin by regulating its transendothelial movement from blood to the interstitial space. These observations are physiologically significant and critical when considering ways to harness the therapeutic potential of adiponectin for diabetes.
- Subjects :
- Male
medicine.medical_specialty
Biodistribution
Endothelium
Physiology
Endocrinology, Diabetes and Metabolism
Adipokine
Vascular permeability
Peptide hormone
medicine.disease_cause
Fluorescence
Cell Line
Diabetes Mellitus, Experimental
Capillary Permeability
Mice
Physiology (medical)
Internal medicine
medicine
Animals
Humans
Tissue Distribution
Rats, Wistar
Tomography
Adiponectin
Chemistry
Microcirculation
Myocardium
Endothelial Cells
Streptozotocin
Rats
Mice, Inbred C57BL
Glucose
Endocrinology
medicine.anatomical_structure
Liver
Gene Knockdown Techniques
Tomography, X-Ray Computed
Oxidative stress
Research Article
medicine.drug
Subjects
Details
- ISSN :
- 15221555 and 01931849
- Volume :
- 317
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Endocrinology and Metabolism
- Accession number :
- edsair.doi.dedup.....7400d238f7cca440ba0b33e752253f26