Acute hypoxia induces hypertriglyceridemia by decreasing plasma triglyceride clearance in mice

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Citações na Scopus
68
Tipo de produção
article
Data de publicação
2012
Título da Revista
ISSN da Revista
Título do Volume
Editora
AMER PHYSIOLOGICAL SOC
Autores
JUN, Jonathan C.
SHIN, Mi-Kyung
YAO, Qiaoling
BEVANS-FONTI, Shannon
POOLE, James
POLOTSKY, Vsevolod Y.
Citação
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, v.303, n.3, p.E377-E388, 2012
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Obstructive sleep apnea (OSA) induces intermittent hypoxia (IH) during sleep and is associated with elevated triglycerides (TG). We previously demonstrated that mice exposed to chronic IH develop elevated TG. We now hypothesize that a single exposure to acute hypoxia also increases TG due to the stimulation of free fatty acid (FFA) mobilization from white adipose tissue (WAT), resulting in increased hepatic TG synthesis and secretion. Male C57BL6/J mice were exposed to FiO(2) = 0.21, 0.17, 0.14, 0.10, or 0.07 for 6 h followed by assessment of plasma and liver TG, glucose, FFA, ketones, glycerol, and catecholamines. Hypoxia dose-dependently increased plasma TG, with levels peaking at FiO(2) = 0.07. Hepatic TG levels also increased with hypoxia, peaking at FiO(2) = 0.10. Plasma catecholamines also increased inversely with FiO(2). Plasma ketones, glycerol, and FFA levels were more variable, with different degrees of hypoxia inducing WAT lipolysis and ketosis. FiO(2) = 0.10 exposure stimulated WAT lipolysis but decreased the rate of hepatic TG secretion. This degree of hypoxia rapidly and reversibly delayed TG clearance while decreasing [H-3]triolein-labeled Intralipid uptake in brown adipose tissue and WAT. Hypoxia decreased adipose tissue lipoprotein lipase (LPL) activity in brown adipose tissue and WAT. In addition, hypoxia decreased the transcription of LPL, peroxisome proliferator-activated receptor-gamma, and fatty acid transporter CD36. We conclude that acute hypoxia increases plasma TG due to decreased tissue uptake, not increased hepatic TG secretion.
Palavras-chave
lipolysis, lipases, adipose, thermoregulation, metabolism
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