Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Department of Pathology, School of Medicine, Saint Louis University, St Louis, MO 63104, USA.
Biomed Pharmacother. 2018 Jan;97:339-348. doi: 10.1016/j.biopha.2017.07.168. Epub 2017 Nov 6.
Intracellular lipid droplets (LDs) are remarkably dynamic and complex organelles that enact regulated storage and release of lipids to fulfil their fundamental roles in energy metabolism, membrane synthesis and provision of lipid-derived signaling molecules. The recent finding that LDs can be selectively degraded by the lysosomal pathway of autophagy through a process termed lipophagy has opened up a new understanding of how lipid metabolism regulates cellular physiology and pathophysiology. Many new functions for autophagic lipid metabolism have now been defined in various diseases including liver disease. Lipophagy was originally described in hepatocytes, where it is critical for maintaining cellular energy homeostasis in obesity and metabolic syndrome. In vitro and in vivo studies have demonstrated the selective uptake of LDs by autophagosomes, and inhibition of autophagy has been shown to reduce the β-oxidation of free fatty acids due to the increased accumulation of lipids and LDs. The identification of lipophagy as a new process dedicated to cellular lipid removal has mapped autophagy as an emerging player in cellular lipid metabolism. Pharmacological or genetic modulation of lipophagy might point to possible therapeutic strategies for combating a broad range of liver diseases. This review summarizes recent work focusing on lipophagy and liver disease as well as highlighting challenges and future directions of research. On the other hand, it also offers a glimpse into different strategies that have been used in experimental models to counteract excessive pathological lipophagy in the prevention and treatment of liver disease.
细胞内脂滴 (LDs) 是一种显著动态且复杂的细胞器，通过调节脂质的储存和释放来发挥其在能量代谢、膜合成和提供脂质衍生的信号分子中的基本作用。最近发现，LDs 可以通过自噬溶酶体途径被选择性降解，这一过程被称为脂噬作用，这为理解脂质代谢如何调节细胞生理学和病理生理学开辟了新的思路。现在已经在许多疾病中定义了自噬性脂质代谢的许多新功能，包括肝病。脂噬作用最初在肝细胞中被描述，在肥胖症和代谢综合征中，它对维持细胞能量平衡至关重要。体外和体内研究表明，自噬体可以选择性地摄取 LDs，并且抑制自噬会由于脂质和 LDs 的积累增加而减少游离脂肪酸的 β-氧化。将脂噬作用鉴定为一种专门用于细胞脂质去除的新过程，将自噬作用定位为细胞脂质代谢中的一个新兴参与者。脂噬作用的药理学或遗传学调节可能为治疗广泛的肝脏疾病提供可能的治疗策略。这篇综述总结了最近关于脂噬作用与肝病的研究工作，强调了研究的挑战和未来方向。另一方面，它还提供了一些在实验模型中用于对抗过度病理性脂噬作用的不同策略的简要概述，以预防和治疗肝病。
