Intermittent hypoxia exacerbates metabolic effects of diet-induced obesity

Luciano F. Drager, Jianguo Li, Christian Reinke, Shannon Bevans-Fonti, Jonathan Jun, Vsevolod Polotsky

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2167-2174
Number of pages8
JournalObesity
Volume19
Issue number11
DOIs
StatePublished - Nov 2011

Fingerprint

Obesity
Diet
Homeostasis
Insulin Resistance
Glucose Intolerance
Sleep Apnea Syndromes
Blood Glucose
Hypoxia
Fasting
Insulin
Liver
Fatty Liver
Glucose Tolerance Test
Inbred C57BL Mouse
Oxidative Stress
Fats
Air
Body Weight
Inflammation
Glucose

ASJC Scopus subject areas

  • Endocrinology
  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cite this

Intermittent hypoxia exacerbates metabolic effects of diet-induced obesity. / Drager, Luciano F.; Li, Jianguo; Reinke, Christian; Bevans-Fonti, Shannon; Jun, Jonathan; Polotsky, Vsevolod.

In: Obesity, Vol. 19, No. 11, 11.2011, p. 2167-2174.

Research output: Contribution to journalArticle

Drager, Luciano F. ; Li, Jianguo ; Reinke, Christian ; Bevans-Fonti, Shannon ; Jun, Jonathan ; Polotsky, Vsevolod. / Intermittent hypoxia exacerbates metabolic effects of diet-induced obesity. In: Obesity. 2011 ; Vol. 19, No. 11. pp. 2167-2174.
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