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棕色脂肪组织:胰高血糖素样肽 1 受体激动剂治疗肥胖的新潜在靶点。

Brown Adipose Tissue: A New Potential Target for Glucagon-like Peptide 1 Receptor Agonists in the Treatment of Obesity.

机构信息

Department of Pediatric Endocrinology, Diabetes and Metabolic Diseases, University Children's Hospital, 1000 Ljubljana, Slovenia.

Department for Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia.

出版信息

Int J Mol Sci. 2023 May 11;24(10):8592. doi: 10.3390/ijms24108592.

Abstract

Adipose tissue can be divided into white adipose tissue (WAT), brown adipose tissue (BAT), and beige adipose tissue, according to the differences in morphology. WAT acts as a buffer for increased energy intake and decreased energy expenditure during the development of obesity, resulting in visceral and ectopic WAT accumulation. These WAT depots are strongly associated with chronic systemic inflammation, insulin resistance, and cardiometabolic risk related to obesity. They represent a primary weight loss target in anti-obesity management. Second-generation anti-obesity medications glucagon-like peptide-1 receptor agonists (GLP-1RAs) cause weight loss and improve body composition by reducing visceral and ectopic fat depots of WAT, resulting in improved cardiometabolic health. Recently, the understanding of the physiological significance of BAT beyond its primary function in generating heat through non-shivering thermogenesis has been expanded. This has raised scientific and pharmaceutical interest in the manipulation of BAT to further enhance weight reduction and body weight maintenance. This narrative review focuses on the potential impact of GLP-1 receptor agonism on BAT, particularly in human clinical studies. It provides an overview of the role of BAT in weight management and highlights the need for further research to elucidate the mechanisms by which GLP-1RAs affect energy metabolism and weight loss. Despite encouraging preclinical data, limited clinical evidence supports the notion that GLP-1RAs contribute to BAT activation.

摘要

根据形态学的差异,脂肪组织可分为白色脂肪组织(WAT)、棕色脂肪组织(BAT)和米色脂肪组织。在肥胖的发展过程中,WAT 充当了能量摄入增加和能量消耗减少的缓冲器,导致内脏和异位 WAT 积累。这些 WAT 储库与慢性全身炎症、胰岛素抵抗以及与肥胖相关的心脏代谢风险密切相关。它们是抗肥胖管理中减轻体重的主要目标。第二代抗肥胖药物胰高血糖素样肽-1 受体激动剂(GLP-1RAs)通过减少 WAT 的内脏和异位脂肪沉积来引起体重减轻和改善身体成分,从而改善心脏代谢健康。最近,人们对 BAT 的生理意义的理解已经超出了其通过非颤抖性产热产生热量的主要功能,这引起了科学界和制药界对操纵 BAT 以进一步增强减肥和体重维持的兴趣。本综述重点介绍了 GLP-1 受体激动剂对 BAT 的潜在影响,特别是在人类临床研究中。它概述了 BAT 在体重管理中的作用,并强调需要进一步研究阐明 GLP-1RAs 影响能量代谢和体重减轻的机制。尽管有令人鼓舞的临床前数据,但有限的临床证据支持 GLP-1RAs 有助于 BAT 激活的观点。

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