The Role of Lipophagy in the Development and Treatment of Non-Alcoholic Fatty Liver Disease
Aldo Grefhorst,Ivo P van de Peppel,Lars E. Larsen,Lars E. Larsen,Johan W. Jonker,Adriaan G. Holleboom +5 more
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TLDR
In this paper, the role of hepatic lipid homeostasis in NAFLD and specifically review the current literature on lipophagy, describing its underlying mechanism, its role in pathophysiology and its potential as a therapeutic target.Abstract:
Non-alcoholic fatty liver disease (NAFLD) or metabolic (dysfunction) associated liver disease (MAFLD), is, with a global prevalence of 25%, the most common liver disorder worldwide. NAFLD comprises a spectrum of liver disorders ranging from simple steatosis to steatohepatitis, fibrosis, cirrhosis and eventually end-stage liver disease. The cause of NAFLD is multifactorial with genetic susceptibility and an unhealthy lifestyle playing a crucial role in its development. Disrupted hepatic lipid homeostasis resulting in hepatic triglyceride accumulation is an hallmark of NAFLD. This disruption is commonly described based on four pathways concerning 1) increased fatty acid influx, 2) increased de novo lipogenesis, 3) reduced triglyceride secretion, and 4) reduced fatty acid oxidation. More recently, lipophagy has also emerged as pathway affecting NAFLD development and progression. Lipophagy is a form of autophagy (i.e. controlled autolysosomal degradation and recycling of cellular components), that controls the breakdown of lipid droplets in the liver. Here we address the role of hepatic lipid homeostasis in NAFLD and specifically review the current literature on lipophagy, describing its underlying mechanism, its role in pathophysiology and its potential as a therapeutic target.read more
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The regulation, function, and role of lipophagy, a form of selective autophagy, in metabolic disorders
Shuang Zhang,Xueqiang Peng,Shuo Yang,Xinyu Li,Ming-Lih Huang,Shibo Wei,Jiaxing Liu,Guangpeng He,Hongyu Zheng,Liang Wang,Han Li,Qing Fan +11 more
TL;DR: The role of lipophagy in cancer and other human diseases is poorly understood, although analysis of specific autophagy receptors has helped to expand the diversity of chemotherapeutic targets as mentioned in this paper .
Journal ArticleDOI
Emerging Roles of Impaired Autophagy in Fatty Liver Disease and Hepatocellular Carcinoma.
TL;DR: In this paper, the authors summarized how impaired autophagy affects liver function and contributes to NAFLD, alcoholic fatty liver disease (AFLD), and hepatocellular carcinoma (HCC).
Journal ArticleDOI
Selective PPARα Modulator Pemafibrate and Sodium-Glucose Cotransporter 2 Inhibitor Tofogliflozin Combination Treatment Improved Histopathology in Experimental Mice Model of Non-Alcoholic Steatohepatitis
Kentaro Murakami,Yu F. Sasaki,Masato Asahiyama,Wataru Yano,Toshiaki Takizawa,Wakana Kamiya,Yoshihiro Matsumura,Motonobu Anai,Tsuyoshi Osawa,Jean-Charles Fruchart,Jamila Fruchart-Najib,Hiroyuki Aburatani,Juro Sakai,Tatsuhiko Kodama,Toshiya Tanaka +14 more
TL;DR: Pema and Tofo treatment significantly improved survival rates and reduced the number of tumors in the liver compared to the NASH control group, suggesting that SPPARMα and SGLT2 inhibitor combination therapy has therapeutic potential to prevent NASH-HCC progression.
Journal ArticleDOI
Phloretin mitigates oxidative injury, inflammation and fibrogenic responses via restoration of autophagic flux in in-vitro and pre-clinical models of NAFLD.
TL;DR: In this article , the authors investigated the potential of phloretin to maintain redox equilibrium and prevent disease progression via modulation of autophagy in NAFLD via upregulating autoophagy-mediated lipid breakdown and inhibited oxidative damage, hepatic inflammation and fibrosis.
Journal ArticleDOI
SIRT1 prevents cigarette smoking-induced lung fibroblasts activation by regulating mitochondrial oxidative stress and lipid metabolism
Yue-Jun Zhang,Ting Ting Li,Miao-Xia Pan,Wei Wang,Wenhui Huang,Ya-Juan Yuan,Zhan-Li Xie,Yixin Chen,Juan Peng,Xue Li,Ying Meng +10 more
TL;DR: In this article , the effect of 1% cigarette smoking extract (CSE) on mtROS level by MitoSOX™ indicator was investigated and the effect was shown to be increased mtNOX4 and decreased SOD2, and the role of autophagy on lipid metabolism and LF activation was explored.
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