Mitochondrial uncoupler BAM15 reverses diet-induced obesity and insulin resistance in mice
Mitochondrial uncoupler BAM15 reverses diet-induced obesity and insulin resistance in mice
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DOI：
10.1038/s41467-020-16298-2
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发表时间：
2020-05-14
影响因子：
16.6
通讯作者：
Hoehn, Kyle L.
中科院分区：
文献类型：
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作者：
Alexopoulos, Stephanie J.;Chen, Sing-Young;Hoehn, Kyle L.
肥胖是一个健康问题，影响超过40%的美国成年人和13%的全球人口。目前为止，包括饮食、运动、手术和药物治疗在内的抗肥胖治疗都未能逆转肥胖的发生率。在此，我们用通过线粒体解偶联降低热量效率的药理学方法来靶向肥胖。我们表明，最近确定的线粒体解偶联剂BAM 15是口服生物利用度，增加营养氧化，并减少身体脂肪量，而不改变食物摄入量，瘦体重，体温，或生化和血液学指标的毒性。BAM 15减少肝脏脂肪，减少炎症脂质，并具有强抗氧化作用。高胰岛素-正葡萄糖钳夹研究表明，BAM 15改善多种组织类型中的胰岛素敏感性。总的来说，这些数据表明，与BAM 15的药理学线粒体解偶联具有强大的抗肥胖和胰岛素增敏作用，而不损害瘦体重或影响食物摄入。肥胖是一种全球性流行病，治疗选择有限。在这里，作者在小鼠中显示了线粒体解偶联剂BAM 15有效诱导脂肪减少而不影响食物摄入或影响瘦体重的证据。
Obesity is a health problem affecting more than 40% of US adults and 13% of the global population. Anti-obesity treatments including diet, exercise, surgery and pharmacotherapies have so far failed to reverse obesity incidence. Herein, we target obesity with a pharmacotherapeutic approach that decreases caloric efficiency by mitochondrial uncoupling. We show that a recently identified mitochondrial uncoupler BAM15 is orally bioavailable, increases nutrient oxidation, and decreases body fat mass without altering food intake, lean body mass, body temperature, or biochemical and haematological markers of toxicity. BAM15 decreases hepatic fat, decreases inflammatory lipids, and has strong antioxidant effects. Hyperinsulinemic-euglycemic clamp studies show that BAM15 improves insulin sensitivity in multiple tissue types. Collectively, these data demonstrate that pharmacologic mitochondrial uncoupling with BAM15 has powerful anti-obesity and insulin sensitizing effects without compromising lean mass or affecting food intake. Obesity is a global pandemic with limited treatment options. Here, the authors show evidence in mice that the mitochondrial uncoupler BAM15 effectively induces fat loss without affecting food intake or compromising lean body mass.