Lutz Thomas A, Osto Elena
aInstitute of Veterinary Physiology, Vetsuisse Faculty University of Zurich bCenter for Integrative Human Physiology, University of Zurich, Zurich cInstitute for Food Nutrition and Health, Laboratory of Translational Nutritional Biology, ETH Zurich, Schwerzenbach dCenter for Molecular Cardiology, University of Zurich, Schlieren, Switzerland.
Curr Opin Lipidol. 2016 Jun;27(3):257-63. doi: 10.1097/MOL.0000000000000293.
Glucagon-like peptide-1 (GLP-1) is the best known incretin hormone able to potentiate glucose-induced insulin secretion. Moreover, GLP-1 is currently under intensive investigation as a potential crucial mediator of beneficial metabolic effects after bariatric surgery, because of its eating inhibitory, antiobesity, and antidiabetes effects. This review briefly summarizes recent findings on the specific effects of GLP-1 on lipoprotein metabolism. The related hormone GLP-2 is derived from the same precursor gene; its effects on lipoprotein metabolism will also be discussed briefly.
Pharmacological activation of the GLP-1 system has beneficial effects on obesity-induced alterations of lipoprotein metabolism. These benefits can be observed with direct GLP-1 receptor agonists like liraglutide or exendin-4, but also with inhibitors of dipeptidyl peptidase IV (DPP-IV), which reduce the breakdown of endogenous GLP-1. The role of GLP-2-related pathways on lipid levels and metabolism are less clear, but some effects (e.g. increased intestinal chylomicron output) are opposite to GLP-1.
Activation of the GLP-1-dependent pathways may perhaps translate into a lower cardiovascular risk. Understanding how GLP-1 and GLP-2 regulate and interact in the control of lipoprotein metabolism will set the stage for the development of new strategies to treat dyslipidaemia in obesity, diabetes, and other cardiometabolic diseases.
胰高血糖素样肽-1(GLP-1)是最著名的肠促胰岛素激素,能够增强葡萄糖诱导的胰岛素分泌。此外,由于其抑制进食、抗肥胖和抗糖尿病作用,GLP-1目前作为减肥手术后有益代谢效应的潜在关键介质正受到深入研究。本综述简要总结了GLP-1对脂蛋白代谢特定作用的最新研究结果。相关激素GLP-2来源于同一前体基因;也将简要讨论其对脂蛋白代谢的作用。
GLP-1系统的药理学激活对肥胖诱导的脂蛋白代谢改变具有有益作用。使用利拉鲁肽或艾塞那肽-4等直接GLP-1受体激动剂以及降低内源性GLP-1降解的二肽基肽酶IV(DPP-IV)抑制剂均可观察到这些益处。GLP-2相关途径对血脂水平和代谢的作用尚不清楚,但某些作用(如肠道乳糜微粒输出增加)与GLP-1相反。
激活GLP-1依赖性途径可能会降低心血管风险。了解GLP-1和GLP-2在脂蛋白代谢控制中的调节和相互作用方式,将为制定治疗肥胖、糖尿病和其他心脏代谢疾病中血脂异常的新策略奠定基础。