Beneficial effects of simultaneously targeting calorie intake and calorie efficiency in diet-induced obese mice.
Beneficial effects of simultaneously targeting calorie intake and calorie efficiency in diet-induced obese mice.
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同时针对饮食诱导的肥胖小鼠的卡路里摄入量和卡路里效率的有益效果。
DOI：
10.1042/cs20231016
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Hoehn,KyleL
中科院分区：
文献类型：
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作者：
Chen,Sing-Young;Telfser,AidenJ;Olzomer,EllenM;Vancuylenberg,CalumS;Zhou,Mingyan;Beretta,Martina;Li,Catherine;Alexopoulos,StephanieJ;Turner,Nigel;Byrne,FrancesL;Santos,WebsterL;Hoehn,KyleL
Semaglutide是一种抗糖尿病和减肥药物，可以减少食物摄入，减缓胃排空，增加胰岛素分泌。患者开始使用低剂量的西马鲁肽治疗，并随着时间的推移增加剂量，以达到疗效稳定。随着剂量的增加，胃肠道副作用的发生率也会增加。尽管食物摄入量持续较低，但西马鲁肽的功效仍处于平台期，其中一个原因是由于代偿作用，即身体的代谢效率提高，以抵御进一步的体重减轻。线粒体解耦剂药物会降低代谢效率，因此我们试图研究西马鲁肽与线粒体解耦剂BAM15在饮食诱导的肥胖小鼠中的联合治疗。饲喂高脂西餐（WD），将小鼠分为对照组、BAM15组、低剂量不含BAM15组、高剂量不含BAM15组和高剂量不含BAM15组。BAM15与任何一种剂量的西马鲁肽联合使用均能降低体脂和肝脏甘油三酯，这是任何单一治疗都无法达到的，而高剂量的西马鲁肽与BAM15联合使用对葡萄糖稳态的影响最大。该研究展示了一种新的方法，可以在不损失瘦质量的情况下改善体重减轻，并通过同时瞄准能量摄入和能量效率来改善葡萄糖控制。这样的组合可以减少对西马鲁肽剂量增加的需要，从而最大限度地减少潜在的胃肠道副作用。
Semaglutide is an anti-diabetes and weight loss drug that decreases food intake, slows gastric emptying, and increases insulin secretion. Patients begin treatment with low-dose semaglutide and increase dosage over time as efficacy plateaus. With increasing dosage, there is also greater incidence of gastrointestinal side effects. One reason for the plateau in semaglutide efficacy despite continued low food intake is due to compensatory actions whereby the body becomes more metabolically efficient to defend against further weight loss. Mitochondrial uncoupler drugs decrease metabolic efficiency, therefore we sought to investigate the combination therapy of semaglutide with the mitochondrial uncoupler BAM15 in diet-induced obese mice. Mice were fed high-fat western diet (WD) and stratified into six treatment groups including WD control, BAM15, low-dose semaglutide without or with BAM15, and high-dose semaglutide without or with BAM15. Combining BAM15 with either semaglutide dose decreased body fat and liver triglycerides, which was not achieved by any monotherapy, while high-dose semaglutide with BAM15 had the greatest effect on glucose homeostasis. This study demonstrates a novel approach to improve weight loss without loss of lean mass and improve glucose control by simultaneously targeting energy intake and energy efficiency. Such a combination may decrease the need for semaglutide dose escalation and hence minimize potential gastrointestinal side effects.