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Sirtuin 1 去乙酰化酶：肝脏脂质代谢的关键调节因子。

Sirtuin 1 deacetylase: a key regulator of hepatic lipid metabolism.

机构信息

Department of Molecular and Integrative Physiology, University of Illinois at Urbana, Urbana, Illinois, USA.

出版信息

Vitam Horm. 2013;91:385-404. doi: 10.1016/B978-0-12-407766-9.00016-X.

DOI:10.1016/B978-0-12-407766-9.00016-X
PMID:23374725
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4976444/
Abstract

Obesity is a serious medical problem worldwide and disruption of metabolic/energy homeostasis plays a pivotal role in this global epidemic. In obese people, fatty liver (steatosis) develops, which increases the risk for diabetes, cardiovascular disease, and even, liver cancer. Sirtuin 1 (SIRT1) is a NAD+-dependent deacetylase that functions as a key metabolic/energy sensor and mediates homeostatic responses to nutrient availability. Accumulating evidence indicates that SIRT1 is a master regulator of the transcriptional networks that control hepatic lipid metabolism. During energy-deprived conditions, SIRT1 deacetylates and alters the expression and activities of key transcriptional regulators involved in hepatic lipogenesis, fatty acid β-oxidation, and cholesterol/bile acid metabolism. This review will discuss the latest advances in this field, focusing on beneficial roles of SIRT1 in hepatic lipid metabolism including its potential as a therapeutic target for treatment of steatosis and other obesity-related metabolic diseases.

摘要

肥胖是一个全球性的严重医学问题，代谢/能量平衡的破坏在这场全球流行疾病中起着关键作用。在肥胖人群中，脂肪肝（脂肪变性）会发展，从而增加患糖尿病、心血管疾病甚至肝癌的风险。Sirtuin 1（SIRT1）是一种 NAD+-依赖性去乙酰化酶，作为关键的代谢/能量传感器，介导对营养可用性的稳态反应。越来越多的证据表明，SIRT1 是控制肝脏脂质代谢的转录网络的主要调节因子。在能量匮乏的情况下，SIRT1 去乙酰化并改变参与肝内脂肪生成、脂肪酸 β-氧化和胆固醇/胆汁酸代谢的关键转录调节剂的表达和活性。本文将讨论该领域的最新进展，重点介绍 SIRT1 在肝脏脂质代谢中的有益作用，包括其作为治疗脂肪变性和其他肥胖相关代谢疾病的治疗靶点的潜力。

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