GLP-1 therapy increases visceral adipose tissue metabolic activity: lessons from a randomized controlled trial in obstructive sleep apnea.

Cliona O'Donnell, Odhrán Ryan, Andrew E Hogan, Desmond Killick, Shane Crilly, Jonathan D Dodd, David J Murphy, Silke Ryan, Donal O'Shea
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Abstract

Objective: Glucagon-like peptide-1 (GLP-1) analogues are currently the most widely used pharmacotherapies for weight loss. Their primary mechanism of action is attributed to reduction in energy intake. Data from murine studies also support an additional impact of those agents on energy homeostasis through upregulation of visceral adipose tissue (VAT) metabolic activity, but this remains uncertain in humans.

Methods: Here, we present data from a proof-of-concept study on 30 individuals with obstructive sleep apnea and obesity who were randomized to a GLP-1 therapy-based weight loss regimen, continuous positive airway pressure, or a combination of both for 24 weeks. At baseline and study completion, 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET-CT) was performed to evaluate VAT metabolic activity, expressed as VAT target to background ratio.

Results: Treatment with GLP-1, but not with continuous positive airway pressure, was associated with a significant increase in VAT target to background ratio. There was a strong correlation between the increase in VAT metabolic activity and the degree of weight loss.

Conclusions: These data support the hypothesis that upregulation of VAT metabolic activity by GLP-1 contributes to its weight loss action in humans, and this subject warrants further detailed investigation.

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GLP-1 疗法可增加内脏脂肪组织的代谢活动:阻塞性睡眠呼吸暂停随机对照试验的启示。
目的:胰高血糖素样肽-1(GLP-1)类似物是目前最广泛使用的减肥药物疗法。它们的主要作用机制是减少能量摄入。方法:在此,我们展示了一项概念验证研究的数据,研究对象是 30 名患有阻塞性睡眠呼吸暂停和肥胖症的患者,他们被随机分配到以 GLP-1 疗法为基础的减肥方案、持续气道正压疗法或两者相结合的减肥方案中,为期 24 周。在基线和研究结束时,进行了18F-氟脱氧葡萄糖(18F-FDG)正电子发射断层扫描(PET-CT),以评估增值血管瘤的代谢活动,用增值血管瘤目标与背景的比率表示:结果:GLP-1(而非持续气道正压)治疗可显著提高增值毛细血管目标与背景比率。VAT代谢活性的增加与体重减轻程度之间存在很强的相关性:这些数据支持这样的假设,即 GLP-1 对增值血管代谢活性的上调有助于其在人体中的减肥作用。
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