Vascular and hepatic impact of short-term intermittent hypoxia in a mouse model of metabolic syndrome

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Abstract

Background: Experimental models of intermittent hypoxia (IH) have been developed during the last decade to investigate the consequences of obstructive sleep apnea. IH is usually associated with detrimental metabolic and vascular outcomes. However, paradoxical protective effects have also been described depending of IH patterns and durations applied in studies. We evaluated the impact of short-term IH on vascular and metabolic function in a diet-induced model of metabolic syndrome (MS). Methods: Mice were fed either a standard diet or a high fat diet (HFD) for 8 weeks. During the final 14 days of each diet, animals were exposed to either IH (1 min cycle, FiO<inf>2</inf> 5% for 30s, FiO<inf>2</inf>21% for 30s; 8 h/day) or intermittent air (FiO<inf>2</inf> 21%). Ex-vivo vascular reactivity in response to acetylcholine was assessed in aorta rings by myography. Glucose, insulin and leptin levels were assessed, as well as serum lipid profile, hepatic mitochondrial activity and tissue nitric oxide (NO) release. Results: Mice fed with HFD developed moderate markers of dysmetabolism mimicking MS, including increased epididymal fat, dyslipidemia, hepatic steatosis and endothelial dysfunction. HFD decreased mitochondrial complex I, II and IV activities and increased lactate dehydrogenase (LDH) activity in liver. IH applied to HFD mice induced a major increase in insulin and leptin levels and prevented endothelial dysfunction by restoring NO production. IH also restored mitochondrial complex I and IV activities, moderated the increase in LDH activity and liver triglyceride accumulation in HFD mice. Conclusion: In a mouse model of MS, short-term IH increases insulin and leptin levels, restores endothelial function and mitochondrial activity and limits liver lipid accumulation.

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Trzepizur, W., Gaceb, A., Arnaud, C., Ribuot, C., Levy, P., Martinez, M. C., … Andriantsitohaina, R. (2015). Vascular and hepatic impact of short-term intermittent hypoxia in a mouse model of metabolic syndrome. PLoS ONE, 10(5). https://doi.org/10.1371/journal.pone.0124637

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