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米拉贝隆:最有前途的脂肪组织褐变剂。

Mirabegron: The most promising adipose tissue beiging agent.

机构信息

Biotechnology Program, Lakehead University, 955 Oliver Road Thunder Bay, ON, Canada.

Northern Ontario School of Medicine, 955 Oliver Road Thunder Bay, ON and 935 Ramsey Lake Road, Sudbury, ON, Canada.

出版信息

Physiol Rep. 2021 Mar;9(5):e14779. doi: 10.14814/phy2.14779.

Abstract

Accumulation of white adipose tissue (WAT) underlies the obesity epidemic, leading to current therapeutic techniques that are being investigated for their ability to activate/"beige" this tissue. Adipose tissue (AT) beiging has been reported through intermittent cold exposure (CE), exercise, and β3-Adrenergic Receptor (β3AR) agonists. But how AT beiging can help in the treatment of metabolic disorders like obesity and type 2 diabetes (T2D) remains largely unexplored. This review summarizes recent research on the use of β3AR agonist, mirabegron (Myrbetriq®), in stimulating beiging in AT. Researchers have only recently been able to determine the optimal therapeutic dose of mirabegron for inducing beiging in subcutaneous/ inguinal WAT, where the benefits of AT activation are evident without the undesired cardiovascular side effects. To determine whether the effects that mirabegron elicits are metabolically beneficial, a comparison of the undisputed findings resulting from intermittent CE-induced beiging and the disputed findings from exercise-induced beiging was conducted. Given the recent in vivo animal and clinical studies, the understanding of how mirabegron can be metabolically beneficial for both lean and obese individuals is more clearly understood. These studies have demonstrated that circulating adipokines, glucose metabolism, and lipid droplet (LD) size are all positively affected by mirabegron administration. Recent studies have also demonstrated that mirabegron has similar outcomes to intermittent CE and displays more direct evidence for beiging than those produced with exercise. With these current findings, mirabegron is considered the most promising and safest β3AR agonist currently available that has the potential to be used in the therapeutic treatment of metabolic disorders, and future studies into its interaction with different conditions may prove to be useful as part of a treatment plan in combination with a healthy diet and exercise.

摘要

白色脂肪组织(WAT)的积累是肥胖流行的基础,导致目前正在研究的治疗技术,以评估其激活/“米色化”这种组织的能力。间歇性冷暴露(CE)、运动和β3 肾上腺素能受体(β3AR)激动剂已报道过脂肪组织(AT)的米色化。但是,AT 的米色化如何有助于治疗肥胖和 2 型糖尿病(T2D)等代谢紊乱,在很大程度上仍未得到探索。本综述总结了最近关于使用β3AR 激动剂米拉贝隆(Myrbetriq®)刺激 AT 米色化的研究。研究人员最近才能够确定米拉贝隆诱导皮下/腹股沟 WAT 米色化的最佳治疗剂量,在这种情况下,AT 激活的益处显而易见,而没有不必要的心血管副作用。为了确定米拉贝隆引起的作用是否具有代谢益处,对间歇性 CE 诱导的米色化的无争议发现和运动诱导的米色化的有争议发现进行了比较。鉴于最近的体内动物和临床研究,人们对米拉贝隆如何对瘦人和肥胖个体都具有代谢益处有了更清楚的认识。这些研究表明,循环脂肪因子、葡萄糖代谢和脂滴(LD)大小都受到米拉贝隆给药的积极影响。最近的研究还表明,米拉贝隆与间歇性 CE 具有相似的结果,并显示出比运动更直接的米色化证据。有了这些当前的发现,米拉贝隆被认为是目前最有前途和最安全的β3AR 激动剂,有可能用于治疗代谢紊乱的治疗,未来对其与不同情况相互作用的研究可能被证明是有用的,可以作为健康饮食和运动相结合的治疗计划的一部分。

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