Intermittent Hypoxia Exacerbates Metabolic Effects of Diet-Induced Obesity

Autor(es)

Drager, Luciano F. ^[1] ; Li, Jianguo ^[1] ; Reinke, Christian ^[1] ; Bevans-Fonti, Shannon ^[1] ; Jun, Jonathan C. ^[1] ; Polotsky, Vsevolod Y. ^[1]

Afiliação do(s) autor(es)

^[1] Johns Hopkins Univ, Sch Med, Dept Med, Div Pulm & Crit Care Med, Baltimore, MD 21205 - USA

• Tipo de documento: Artigo Científico
• Fonte: OBESITY; v. 19, n. 11, p. 2167-2174, NOV 2011.
• Citações Web of Science: 110

Resumo

Obesity causes insulin resistance (IR) and nonalcoholic fatty liver disease (NAFLD), but the relative contribution of sleep apnea is debatable. The main aim of this study is to evaluate the effects of chronic intermittent hypoxia (CIH), a hallmark of sleep apnea, on IR and NAFLD in lean mice and mice with diet-induced obesity (DIO). Mice (C57BL/6J), 6-8 weeks of age were fed a high fat (n = 18) or regular (n = 16) diet for 12 weeks and then exposed to CIH or control conditions (room air) for 4 weeks. At the end of the exposure, fasting (5 h) blood glucose, insulin, homeostasis model assessment (HOMA) index, liver enzymes, and intraperitoneal glucose tolerance test (1 g/kg) were measured. In DIO mice, body weight remained stable during CIH and did not differ from control conditions. Lean mice under CIH were significantly lighter than control mice by day 28 (P = 0.002). Compared to lean mice, DIO mice had higher fasting levels of blood glucose, plasma insulin, the HOMA index, and had glucose intolerance and hepatic steatosis at baseline. In lean mice, CIH slightly increased HOMA index (from 1.79 +/- 0.13 in control to 2.41 +/- 0.26 in CIH; P = 0.05), whereas glucose tolerance was not affected. In contrast, in DIO mice, CIH doubled HOMA index (from 10.1 +/- 2.1 in control to 22.5 +/- 3.6 in CIH; P < 0.01), and induced severe glucose intolerance. In DIO mice, CIH induced NAFLD, inflammation, and oxidative stress, which was not observed in lean mice. In conclusion, CIH exacerbates IR and induces steatohepatitis in DIO mice, suggesting that CIH may account for metabolic dysfunction in obesity. (AU)

• Processo FAPESP: 10/11681-0 - Impacto da hipóxia intermitente no clearance de lipoproteínas e na aterosclerose: uma abordagem translacional
• Beneficiário: Luciano Ferreira Drager
• Linha de fomento: Bolsas no Exterior - Pesquisa