title: Effect of chronic intermittent hypoxia on triglyceride uptake in different tissues.
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 [H(3)]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.
authors: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
authors: Qiaoling
authors: Q
authors: Yao
authors: Mi-Kyung
authors: MK
authors: Shin
authors: Jonathan C
authors: JC
authors: Jun
authors: Karen L
authors: KL
authors: Hernandez
authors: Neil R
authors: NR
authors: Aggarwal
authors: Jason R
authors: JR
authors: Mock
authors: Jason
authors: J
authors: Gay
authors: Luciano F
authors: LF
authors: Drager
authors: Vsevolod Y
authors: VY
authors: Polotsky
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism; D052436:Adipose Tissue, White / Q000378:metabolism; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000860:Hypoxia / Q000503:physiopathology*; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism; D008168:Lung; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; C407088:Angptl4 protein, mouse; D008074:Lipoproteins; D014280:Triglycerides; D008071:Lipoprotein Lipase
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