Effect of chronic intermittent hypoxia on triglyceride uptake in different tissues |
| |
Authors: | Qiaoling Yao Mi-Kyung Shin Jonathan C Jun Karen L Hernandez Neil R Aggarwal Jason R Mock Jason Gay Luciano F Drager Vsevolod Y Polotsky |
| |
Institution: | *Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21224;†College of Engineering, University of Miami, Coral Gables, FL, 33124;§Lexicon Pharmaceuticals Inc., The Woodlands, TX, 77381;**Heart Institute (InCor), University of São Paulo Medical School, 5403-904, São Paulo, Brazil |
| |
Abstract: | Chronic intermittent hypoxia (CIH) inhibits plasma lipoprotein clearance and adipose lipoprotein lipase (LPL) activity in association with upregulation of an LPL inhibitor angiopoietin-like protein 4 (Angptl4). We hypothesize that CIH inhibits triglyceride (TG) uptake via Angptl4 and that an anti-Angptl4-neutralizing antibody would abolish the effects of CIH. Male C57BL/6J mice were exposed to four weeks of CIH or intermittent air (IA) while treated with Ab (30 mg/kg ip once a week). TG clearance was assessed by H3]triolein administration retroorbitally. CIH delayed TG clearance and suppressed TG uptake and LPL activity in all white adipose tissue depots, brown adipose tissue, and lungs, whereas heart, liver, and spleen were not affected. CD146+ CD11b− pulmonary microvascular endothelial cells were responsible for TG uptake in the lungs and its inhibition by CIH. Antibody to Angptl4 decreased plasma TG levels and increased TG clearance and uptake into adipose tissue and lungs in both control and CIH mice to a similar extent, but did not reverse the effects of CIH. The antibody reversed the effects of CIH on LPL in adipose tissue and lungs. In conclusion, CIH inactivates LPL by upregulating Angptl4, but inhibition of TG uptake occurs predominantly via an Angptl4/LPL-independent mechanism. |
| |
Keywords: | lipoprotein clearance brown adipose tissue white adipose tissue obstructive sleep apnea angiopoietin like protein 4 lipoprotein lipase lungs pulmonary microvascular endothelial cells |
本文献已被 ScienceDirect 等数据库收录! |
|