Transendothelial Transport May Determine Adiponectin Oligomer Functions
Academic Article
Overview
Research
Identity
Additional Document Info
View All
Overview
abstract
Adiponectin has exhibited positive effects in regulation of systemic metabolism and insulin sensitivity through tissues such as liver, skeletal muscle, and centrally in the brain. Circulating as oligomers of 90 to 1080kDa, adiponectin must cross the endothelium to have metabolic effects. Our laboratory has reported differential efficacy of these oligomers on insulin sensitivity. Recent data has also demonstrated oligomer sizedependence on adiponectin clearance. Only the small trimeric oligomer is found in cerebral spinal fluid. Here, we have measured the Stokes radii of adiponectin to be approximately 5, 10, and 25nm for the trimeric, hexameric, and high molecular weight (HMW) forms, respectively. The HMW size may present transport limitations across endothelial barriers in muscle or in the brain. Using murine 3B11, MS1, and bEnd3 endothelial cells in transwell permeability studies, we demonstrate that 3B11 and MS1 cells permit equivalent transport of trimeric and HMW adiponectin for their diffusive sizes. The bEnd3 cells, a model of brain endothelium, present an increased barrier to HMW adiponectin. In all cases, however, adiponectin fluxes were less than equivalentlysized dextrans, suggesting the existence of active adiponectin transport mechanisms. These data demonstrate that the effects of different adiponectin oligomers on tissue metabolism may depend on the endothelium in a given tissue.
