Inhibition of Lipolysis Ameliorates Diabetic Phenotype in a Mouse Model of Obstructive Sleep Apnea.
Inhibition of Lipolysis Ameliorates Diabetic Phenotype in a Mouse Model of Obstructive Sleep Apnea.
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抑制脂肪分解可改善阻塞性睡眠呼吸暂停小鼠模型的糖尿病表型。
DOI：
10.1165/rcmb.2015-0315oc
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发表时间：
2016
影响因子：
6.4
通讯作者：
Polak,Jan
中科院分区：
文献类型：
--
作者：
Weiszenstein,Martin;Shimoda,LarissaA;Koc,Michal;Seda,Ondrej;Polak,Jan
阻塞性睡眠呼吸暂停（OSA）与胰岛素抵抗、葡萄糖耐受不良和2型糖尿病有关。介导这种关联的因果机制还没有很好的定义，但是，增加脂肪分解可能涉及。在这里，我们研究了阿昔莫司治疗（脂解抑制剂）对间歇性缺氧（IH）小鼠葡萄糖耐量和胰岛素敏感性的影响。将C57 BL 6/J小鼠暴露于IH或对照条件14天。通过将吸入氧气的分数从20.9%降低到6.5%，60次/h来创建IH。对照暴露是以相同流速输送的空气（吸入氧气的分数，20.9%）。在暴露期间，阿昔莫司在饮用水中提供（0.5 g/ml）。暴露后，进行腹膜内胰岛素（0.5 IU/kg）和葡萄糖（1 g/kg）耐受试验，分离原代脂肪细胞进行脂解实验。IH使空腹血糖升高51%，葡萄糖耐量和胰岛素敏感性分别恶化33%和102%。与此同时，IH使自发性脂解增加264%，并使附睾脂肪量减少15%，脂肪细胞大小减少8%。阿昔莫司治疗防止IH诱导的脂解，并增加附睾脂肪量和脂肪细胞大小分别为19%和10%。阿昔莫司可完全预防IH诱导的空腹血糖、葡萄糖耐量和胰岛素敏感性损害。对于所有报告的结果，认为P <0.05具有显著性。在暴露于IH的小鼠中观察到的脂肪分解增加导致胰岛素抵抗和葡萄糖耐受不良。阿昔莫司治疗改善了IH的代谢后果，可能是阻塞性睡眠呼吸暂停患者的一种新的治疗选择。
Obstructive sleep apnea (OSA) is associated with insulin resistance, glucose intolerance, and type 2 diabetes. Causal mechanisms mediating this association are not well defined; however, augmented lipolysis in adipose might be involved. Here, we investigated the effect of acipimox treatment (lipolysis inhibitor) on glucose tolerance and insulin sensitivity in mice exposed to intermittent hypoxia (IH). C57BL6/J mice were exposed for 14 days to IH or control conditions. IH was created by decreasing the fraction of inspired oxygen from 20.9 to 6.5%, 60 times/h. Control exposure was air (fraction of inspired oxygen, 20.9%) delivered at an identical flow rate. Acipimox was provided in drinking water (0.5 g/ml) during exposures. After exposures, intraperitoneal insulin (0.5 IU/kg) and glucose (1 g/kg) tolerance tests were performed, and primary adipocytes were isolated for lipolysis experiments. IH elevated fasting glucose by 51% and worsened glucose tolerance and insulin sensitivity by 33 and 102%, respectively. In parallel, IH increased spontaneous lipolysis by 264%, and reduced epididymal fat mass by 15% and adipocyte size by 8%. Acipimox treatment prevented IH-induced lipolysis and increased epididymal fat mass and adipocyte size by 19 and 10%, respectively. Acipimox fully prevented IH-induced impairments in fasting glycemia, glucose tolerance, and insulin sensitivity. For all reported results,Pless than 0.05 was considered significant. Augmented lipolysis contributes to insulin resistance and glucose intolerance observed in mice exposed to IH. Acipimox treatment ameliorated the metabolic consequences of IH and might represent a novel treatment option for patients with obstructive sleep apnea.
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DOI：
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发表时间：
1968
期刊：
Biochimica et Biophysica Acta
影响因子：
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R. Cowgill
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期刊：
The Journal of biological chemistry
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1975
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影响因子：
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作者：
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