Ouimet Mireille
Department of Medicine, New York University School of Medicine, New York, NY 10016, USA.
Biochim Biophys Acta. 2013 Jun;1831(6):1124-33. doi: 10.1016/j.bbalip.2013.03.007. Epub 2013 Mar 29.
The incidence of diseases characterized by a dysregulation of lipid metabolism such as obesity, diabetes and atherosclerosis is rising at alarming rates, driving research to uncover new therapies to manage dyslipidemias and resolve the metabolic syndrome conundrum. Autophagy and lipid homeostasis - both ancient cellular pathways - have seemingly co-evolved to share common regulatory elements, and autophagy has emerged as a prominent mechanism involved in the regulation of lipid metabolism. This review highlights recent findings on the role of autophagy in the regulation of cellular cholesterol homeostasis and lipoprotein metabolism, with special emphasis on macrophages. From modulation of inflammation to regulation of cellular cholesterol levels, a protective role for autophagy in atherosclerosis is emerging. The manipulation of autophagic activity represents a new possible therapeutic approach for the treatment complex metabolic disorders such as obesity and the metabolic syndrome.
以脂质代谢失调为特征的疾病,如肥胖症、糖尿病和动脉粥样硬化,其发病率正以惊人的速度上升,这推动了相关研究,以探寻治疗血脂异常和解决代谢综合征难题的新疗法。自噬和脂质稳态——这两种古老的细胞途径——似乎共同进化,共享共同的调控元件,并且自噬已成为参与脂质代谢调节的一个重要机制。本综述重点介绍了自噬在细胞胆固醇稳态和脂蛋白代谢调节中作用的最新研究发现,特别强调了巨噬细胞。从炎症调节到细胞胆固醇水平调节,自噬在动脉粥样硬化中发挥的保护作用正逐渐显现。操纵自噬活性代表了一种治疗肥胖症和代谢综合征等复杂代谢紊乱疾病的新的可能治疗方法。