Lipid-induced DRAM recruits STOM to lysosomes and induces LMP to promote exosome release from hepatocytes in NAFLD

Zhang, Jie; Tan, Jie; Wang, Mengke; Wang, Yifen; Dong, Mingjie; Ma, Xuefeng; Sun, Baoqing; Liu, Shousheng; Zhao, Zhenzhen; Chen, Lizhen; Li, Kai; Xin, Yongning; Zhuang, Likun

doi:10.1126/sciadv.abh1541

Cited by 23 publications

(16 citation statements)

References 40 publications

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“…For example, plasma exosome levels are significantly elevated in MAFLD patients. Fatty acid-induced damage-regulated autophagy modulator (DRAM) enhances hepatocyte-associated exosome release by promoting lysosomal localization of stomatin upon interaction with stomatin, which may serve as a potential biomarker of MAFLD ( 80 ). The presence of many membrane-bound vesicles generated by hepatocytes in experimental mice with steatohepatitis that respond to FFA-derived EVs correlates significantly with disease severity ( 81 ).…”

Section: Gut Microbial-derived Evs As An Important Mediator Of the As...mentioning

confidence: 99%

The Potential Role of Gut Microbial-Derived Exosomes in Metabolic-Associated Fatty Liver Disease: Implications for Treatment

et al. 2022

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The prevalence and incidence of metabolic-associated fatty liver disease (MAFLD), a clinically heterogeneous disease whose primary clinical therapies include dietary control and exercise therapy, is increasing worldwide and constitutes a significant medical burden. Gut microbes influence the physiopathological processes of the liver through different mechanisms based on the gut-liver axis. Exosomes are essential carriers of intercellular communication. Most previous studies have focused on adipocyte- and hepatocyte-derived exosomes, while the critical role of microbial-derived exosomes and the molecular mechanisms behind them in MAFLD have received little attention. Therefore, we searched and screened the latest relevant studies in the PubMeb database to elucidate the link between microbial-derived exosomes and the pathogenesis of MAFLD, mainly in terms of insulin resistance, intestinal barrier, inflammatory response, lipid metabolism, and liver fibrosis. The aim was to provide a theoretical framework and support for clinical protocols and innovative drug development.

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Section: Gut Microbial-derived Evs As An Important Mediator Of the As...mentioning

confidence: 99%

The Potential Role of Gut Microbial-Derived Exosomes in Metabolic-Associated Fatty Liver Disease: Implications for Treatment

et al. 2022

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“…In MAFLD patients, damage-regulated autophagy modulator (DRAM) could recruit stomatin (STOM) and increase the lysosomal membrane permeabilization. MVBs were degraded less and released more exosomes ( Zhang et al, 2021 ).…”

Section: What Are Extracellular Vesicles?mentioning

confidence: 99%

Extracellular Vesicles in Pathogenesis and Treatment of Metabolic Associated Fatty Liver Disease

Sun

Zhang

2022

Front. Physiol.

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Metabolic associated fatty liver disease (MAFLD) is the most common chronic liver disease worldwide due to the sedentary and overeating lifestyle. Yet, the pathophysiology of MAFLD is still unclear and no drug has been approved for MAFLD treatment. Extracellular vesicles (EVs) are heterogenous membrane-bound particles released from almost all types of cells. These nano-sized particles mediate intercellular communication through their bioactive cargos including nucleic acids, proteins, and lipids. The EVs modulate metabolic homeostasis via communication between adipose tissue and liver. The dysregulation of lipid metabolism leads to inflammation in liver and the number and compounds of EVs are changed during MAFLD. The injured hepatocytes secrete EVs to induce the migration of bone marrow-derived monocytes and the activation of macrophages in liver. The EVs secreted by different cells regulate the alteration of hepatic stellate cell (HSC) phenotypes and HSC activation gives rise to liver fibrosis. Based on the participation of EVs in MAFLD progression, we discuss the prospects of EVs as a therapeutic target and their application in drug delivery.

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“…Cytosolic free fatty acids damage cellular membranes and membrane‐associated proteins, including those of the lysosomes. Lysosome membrane permeabilization 18 and disassembly of the V‐ATPase protein complex, 19 that acts as the lysosomal proton pump, impair luminal acidification, 19 which results in deficient LAL maturation and activity. Reduced LAL activity slows down lipid catabolism and results in lipid accumulation.…”

Section: Lysosomal Acid Lipase (Lal)mentioning

confidence: 99%

Targeting the lysosome: Mechanisms and treatments for nonalcoholic fatty liver disease

2022

J of Cellular Biochemistry

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The multiple functions of the lysosome, including degradation, nutrient sensing, signaling, and gene regulation, enable the lysosome to regulate lipid metabolism at different levels. In this review, I summarize the recent studies on lysosomal regulation of lipid metabolism and the alterations of the lysosome functions in the livers affected by nonalcoholic fatty liver disease (NAFLD). NAFLD is a highly prevalent lipid metabolic disorder. The progression of NAFLD leads to nonalcoholic steatohepatitis (NASH) and other severe liver diseases, and thus the prevention and treatments of NAFLD progression are critically needed. Targeting the lysosome is a promising strategy. I also discuss the current manipulations of the lysosome functions in the preclinical studies of NAFLD and propose my perspectives on potential future directions.

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Lipid-induced DRAM recruits STOM to lysosomes and induces LMP to promote exosome release from hepatocytes in NAFLD

Abstract: DRAM-mediated mechanism participates in lipid-induced exosome secretion from hepatic cells in NAFLD.

Cited by 23 publications

References 40 publications

The Potential Role of Gut Microbial-Derived Exosomes in Metabolic-Associated Fatty Liver Disease: Implications for Treatment

The Potential Role of Gut Microbial-Derived Exosomes in Metabolic-Associated Fatty Liver Disease: Implications for Treatment

Extracellular Vesicles in Pathogenesis and Treatment of Metabolic Associated Fatty Liver Disease

Targeting the lysosome: Mechanisms and treatments for nonalcoholic fatty liver disease

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