Program in Molecular Medicine, Research Institute, The Hospital for Sick Children and Departments of Laboratory Medicine and Pathobiology, Biochemistry, and Physiology, University of Toronto, Toronto, Ontario M5G 1X8, Canada.
Program in Molecular Medicine, Research Institute, The Hospital for Sick Children and Departments of Laboratory Medicine and Pathobiology, Biochemistry, and Physiology, University of Toronto, Toronto, Ontario M5G 1X8, Canada.
Biochim Biophys Acta Mol Cell Biol Lipids. 2019 Mar;1864(3):326-334. doi: 10.1016/j.bbalip.2018.12.010. Epub 2018 Dec 19.
Non-alcoholic fatty liver disease (NAFLD) is a continuum of disorders that can range from simple steatosis to non-alcoholic steatohepatitis (NASH). As a complex metabolic disorder, the pathophysiology of NAFLD is incompletely understood. Recently glucagon-like peptide (GLP)-1 and -2 signalling has been implicated in the pathogenesis of NAFLD. The role of these gut hormones in the hepatic abnormalities is complicated by lack of consensus on the presence of GLP-1 and GLP-2 receptors within the liver. Nevertheless, GLP-1 and GLP-2 receptor agonists have been associated with alterations in lipid metabolism and hepatic and systemic inflammation, pathological abnormalities characteristic of NAFLD. Treatment with GLP-1 analogues has been shown to reverse features of NAFLD including insulin resistance, and alterations in hepatic de novo lipogenesis and reactive oxygen species. In this review, we provide an overview of the role of GLP-1 and GLP-2 in lipid homeostasis and metabolic disease including NAFLD and NASH.
非酒精性脂肪性肝病 (NAFLD) 是一种连续的疾病谱，可从单纯性脂肪变性到非酒精性脂肪性肝炎 (NASH)。作为一种复杂的代谢紊乱，NAFLD 的病理生理学尚未完全清楚。最近，胰高血糖素样肽 (GLP)-1 和 -2 信号转导被认为与 NAFLD 的发病机制有关。这些肠道激素在肝脏异常中的作用因缺乏对肝脏内 GLP-1 和 GLP-2 受体存在的共识而变得复杂。然而，GLP-1 和 GLP-2 受体激动剂与脂质代谢和肝及全身炎症的改变有关，这些病理异常是 NAFLD 的特征。GLP-1 类似物的治疗已被证明可以逆转 NAFLD 的特征，包括胰岛素抵抗以及肝从头脂肪生成和活性氧的改变。在这篇综述中，我们概述了 GLP-1 和 GLP-2 在脂质稳态和代谢疾病（包括 NAFLD 和 NASH）中的作用。
