Hyperlipidemia and lipid peroxidation are dependent on the severity of chronic intermittent hypoxia

Li, Jianguo; Savransky, Vladimir; Nanayakkara, Ashika; Smith, P. L.; O’Donnell, Christopher P.; Polotsky, Vsevolod Y.

doi:10.1152/japplphysiol.01081.2006

Cited by 212 publications

(170 citation statements)

References 54 publications

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“…The induction of hyperlipidemia by intermit tent hypoxia occurs under severe hypoxia (5% nadir of inspired O 2 ) but not under moderate hypoxia (10%) (29). The finding of similar cholesterol and triglyceride levels in all groups in the present study can be explained by the nadir of inspired O 2 of 7% selected for this study being insufficient to induce hyperlipidemia.…”

Section: Discussioncontrasting

confidence: 46%

Melatonin prevents hyperglycemia in a model of sleep apnea

Kaminski

Martinez

Fagundes

et al. 2015

Arch. Endocrinol. Metab.

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Objective: Obstructive sleep apnea is a common disorder associated with aging and obesity. Apneas cause repeated arousals, intermittent hypoxia, and oxidative stress. Changes in glucolipidic profile occur in apnea patients, independently of obesity. Animal models of sleep apnea induce hyperglycemia. This study aims to evaluate the effect of the antioxidants melatonin and N-acetylcysteine on glucose, triglyceride, and cholesterol levels in animals exposed to intermittent hypoxia. Materials and methods: Two groups of Balb/c mice were exposed to intermittent hypoxia (n = 36) or sham intermittent hypoxia (n = 36) for 35 days. The intermittent hypoxia group underwent a total of 480 cycles of 30 seconds reducing the inspired oxygen fraction from 21% to 7 ± 1% followed by 30 seconds of normoxia, during 8 hours daily. Melatonin or N-acetylcysteine were injected intraperitonially daily from day 21 on. Results: At day 35, glucose levels were significantly higher in the intermittent hypoxia group than in the control group. The intermittent hypoxia groups receiving N-acetylcysteine and vehicle showed higher glucose levels than the group receiving melatonin. The lipid profile was not affected by intermittent hypoxia or antioxidant administration. Conclusions:The present results suggest that melatonin prevents the well-recognized increase in glucose levels that usually follows exposure to intermittent hypoxia. Further exploration of the role of melatonin in sleep apnea is warranted. Arch Endocrinol Metab. 2015;59(1):66-70

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Section: Discussioncontrasting

confidence: 46%

Melatonin prevents hyperglycemia in a model of sleep apnea

Kaminski

Martinez

Fagundes

et al. 2015

Arch. Endocrinol. Metab.

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“…We hypothesize that severe obesity per se acts as ''the first hit'' in the progression of NAFLD inducing hepatic steatosis, whereas the presence of CIH of OSA acts as the ''second hit'' (21), inducing progression of hepatic steatosis to NASH. Our previous experiments in the mouse model showed that CIH increases lipid peroxidation and activates a redox-dependent transcription factor, NF-kB, in the liver (44,45). We have also shown that, in mice with diet-induced hepatic steatosis, but not in mice with normal livers, CIH increases liver levels of proinflammatory cytokines IL-1b, IL-6, macrophage inflammatory protein-2, and tumor necrosis factor-a as well as a1(I) collagen and indices of lobular inflammation and fibrosis (27,45,46).…”

Section: Osa and Nash In Severe Obesitymentioning

confidence: 99%

Obstructive Sleep Apnea, Insulin Resistance, and Steatohepatitis in Severe Obesity

Polotsky

Patil

Savransky

et al. 2009

Am J Respir Crit Care Med

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185

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Rationale: Obstructive sleep apnea is associated with insulin resistance and liver injury. It is unknown whether apnea contributes to insulin resistance and steatohepatitis in severe obesity. Objectives: To examine whether sleep apnea and nocturnal hypoxemia predict the severity of insulin resistance, systemic inflammation, and steatohepatitis in severely obese individuals presenting for bariatric surgery. Methods: We performed sleep studies and measured fasting blood glucose, serum insulin, C-reactive protein, and liver enzymes in 90 consecutive severely obese individuals, 75 women and 15 men, without concomitant diabetes mellitus or preexistent diagnosis of sleep apnea or liver disease. Liver biopsies (n 5 20) were obtained during bariatric surgery. Measurements and Main Results: Obstructive sleep apnea with a respiratory disturbance index greater than 5 events/hour was diagnosed in 81.1% of patients. The median respiratory disturbance index was 15 6 29 events/hour and the median oxygen desaturation during apneic events was 4.6 6 1.8%. All patients exhibited high serum levels of C-reactive protein, regardless of the severity of apnea, whereas liver enzymes were normal. Oxygen desaturation greater than 4.6% was associated with a 1.5-fold increase in insulin resistance, according to the homeostasis model assessment index. Histopathology data suggested that significant nocturnal desaturation might predispose to hepatic inflammation, hepatocyte ballooning, and liver fibrosis. Fasting blood glucose levels and steatosis scores were not affected by nocturnal hypoxia. There was no relationship between the respiratory disturbance index and insulin resistance or liver histopathology. Conclusions: Hypoxic stress of sleep apnea may be implicated in the development of insulin resistance and steatohepatitis in severe obesity.Keywords: hypoxemia; fatty liver disease; metabolic syndrome; sleepdisordered breathing; liver injury Obstructive sleep apnea (OSA) is a complex disorder consisting of upper airway obstruction, chronic intermittent hypoxia (CIH), and sleep fragmentation (1). Epidemiologic studies have demonstrated that OSA is associated with insulin resistance and glucose intolerance, independent of obesity (2-4). Clinical investigations have also shown that OSA results in low-grade systemic inflammation (5, 6). Both insulin resistance and systemic inflammation may contribute to the increased cardiovascular risk in patients with OSA (7-9). Insulin resistance, systemic inflammation, and OSA are particularly prevalent in patients with severe obesity defined as a body mass index (BMI) exceeding 40 kg/m 2 (2, 10-12). While obesity causes systemic inflammation, insulin resistance, and sleep apnea (12-15), sleep apnea may further exacerbate the inflammatory and metabolic disturbances (2, 3, 6). Nevertheless, it is not known whether concomitant OSA is implicated in metabolic dysregulation and systemic inflammation in severe obesity.One of the consequences of obesity and insulin resistance is nonalcoholic fatty liver disease (N...

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“…Recent studies showed that long term IH exposure (up to 12 weeks) with high-fat highcholesterol diet caused atherosclerosis and dyslipidemia in C57BL6 mice, or aggravated both atherosclerotic plaque progression and dyslipidemia in atherosclerosis-prone mice [10][11][12] . In these studies, the metabolic disorder (dyslipidemia and lipid peroxydation) appeared as the main factor linking atherosclerosis to IH.…”

Section: Introductionmentioning

confidence: 99%