Exosomal miR-199a-5p promotes hepatic lipid accumulation by modulating MST1 expression and fatty acid metabolism

Li, Yuhan; Luan, Yansong; Li, Jianning; Song, Hui; Li, Yan; Qi, Hi; Sun, Bo; Zhang, Peng; Wu, Xianxian; Liu, Xing; Yang, Yanhui; Tao, Wufan; Cai, Lei; Yang, Zhiwei; Yang, Yi

doi:10.1007/s12072-020-10096-0

Cited by 44 publications

(37 citation statements)

References 50 publications

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“…EVs are stable in circulating blood and can encapsulate many molecules, and packaging miRNAs (siRNAs or drugs) into EVs represents a promising strategy for the treatment of NAFLD. Li et al packaged miR-199a-5p/anti-miR-199a-5p into exosomes and injected them into mice, resulting in aggravated/attenuated hepatic steatosis, respectively [134]. Additionally, He et al reported the delivery of a miR-146b mimic to hepatocytes through lactosylated PDMAEMA nanoparticles [138].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, a few laboratories have tried to use EVs containing specific miRNAs to affect NAFLD progression. For example, Li et al delivered miR-199a-5p-or anti-miR-199a-5p-containing exosomes to respectively aggravate or ameliorate lipid accumulation in a NAFLD mouse model [134]. However, the clinical translation of treatment based on miRNA-containing EVs is in its infancy and requires substantial investigation and confirmation.…”

Section: Extracellular Vesicles (Evs) In Nafld: Potential Biomarkers and Therapeutic Targetsmentioning

confidence: 99%

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MicroRNAs in the Pathogenesis of Nonalcoholic Fatty Liver Disease

2021

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Nonalcoholic fatty liver disease (NAFLD), or, more accurately, metabolic associated fatty liver disease, accounts for a large proportion of chronic liver disorders worldwide and is closely associated with other conditions such as cardiovascular disease, obesity, and type 2 diabetes mellitus. NAFLD ranges from simple steatosis to nonalcoholic steatohepatitis (NASH) and can progress to cirrhosis and, eventually, also hepatocellular carcinoma. The morbidity and mortality associated with NAFLD are increasing rapidly year on year. Consequently, there is an urgent need to understand the etiology and pathogenesis of NAFLD and identify effective therapeutic targets. MicroRNAs (miRNAs), important epigenetic factors, have recently been proposed to participate in NAFLD pathogenesis. Here, we review the roles of miRNAs in lipid metabolism, inflammation, apoptosis, fibrosis, hepatic stellate cell activation, insulin resistance, and oxidative stress, key factors that contribute to the occurrence and progression of NAFLD. Additionally, we summarize the role of miRNA-enriched extracellular vesicles in NAFLD. These miRNAs may comprise suitable therapeutic targets for the treatment of this condition.

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Section: Discussionmentioning

confidence: 99%

Section: Extracellular Vesicles (Evs) In Nafld: Potential Biomarkers and Therapeutic Targetsmentioning

confidence: 99%

MicroRNAs in the Pathogenesis of Nonalcoholic Fatty Liver Disease

2021

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“…In mice, levels of NAFLD-associated miRNAs such as miR-122 and miR-192 were substantially elevated in circulating EVs after 20 weeks of feeding choline-deficient l-amino acid-defined diet, which causes severe steatosis and inflammation in the liver (Povero et al 2014;Yang et al 2017a). miR-199a-5p was highly upregulated in the steatotic liver of mice on a high-fat diet (HFD; Li et al 2020b). Exosome-associated delivery of miR-199a-5p in mice promoted hepatocyte fat accumulation by downregulation of macrophage stimulating 1 and modulation of genes involved in fatty acid metabolism (Li et al 2020b).…”

Section: Nonalcoholic Fatty Liver Disease (Nafld)mentioning

confidence: 99%

“…miR-199a-5p was highly upregulated in the steatotic liver of mice on a high-fat diet (HFD; Li et al 2020b). Exosome-associated delivery of miR-199a-5p in mice promoted hepatocyte fat accumulation by downregulation of macrophage stimulating 1 and modulation of genes involved in fatty acid metabolism (Li et al 2020b).…”

Section: Nonalcoholic Fatty Liver Disease (Nafld)mentioning

confidence: 99%

Exosomal microRNAs as diagnostic and therapeutic biomarkers in non-malignant liver diseases

Hwang

Yang

2021

Arch. Pharm. Res.

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“…Additionally, miR-124 has been observed to increase phosphorylated-AMPK levels in brain tissues, suggesting a similar role may exist in skeletal muscle [ 51 ]. Upregulated levels of miR-101a and miR-199a are associated with reductions in AMPK signaling and promotion of fatty acid synthesis [ 52 ], and miR-101a can both directly and indirectly inactivate AMPK [ 53 , 54 ]. The seven downregulated miRNAs during hypoxia are also implicated in AMPK signaling in various downstream roles in combating oxidative stress, autophagy and apoptosis during hypoxia, or following anoxia/reoxygenation.…”

Section: Fuel Use: Glucose and Lipidsmentioning

confidence: 99%

Muscles in Winter: The Epigenetics of Metabolic Arrest

Ingelson-Filpula

Storey

2021

Epigenomes

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The winter months are challenging for many animal species, which often enter a state of dormancy or hypometabolism to “wait out” the cold weather, food scarcity, reduced daylight, and restricted mobility that can characterize the season. To survive, many species use metabolic rate depression (MRD) to suppress nonessential metabolic processes, conserving energy and limiting tissue atrophy particularly of skeletal and cardiac muscles. Mammalian hibernation is the best recognized example of winter MRD, but some turtle species spend the winter unable to breathe air and use MRD to survive with little or no oxygen (hypoxia/anoxia), and various frogs endure the freezing of about two-thirds of their total body water as extracellular ice. These winter survival strategies are highly effective, but create physiological and metabolic challenges that require specific biochemical adaptive strategies. Gene-related processes as well as epigenetic processes can lower the risk of atrophy during prolonged inactivity and limited nutrient stores, and DNA modifications, mRNA storage, and microRNA action are enacted to maintain and preserve muscle. This review article focuses on epigenetic controls on muscle metabolism that regulate MRD to avoid muscle atrophy and support winter survival in model species of hibernating mammals, anoxia-tolerant turtles and freeze-tolerant frogs. Such research may lead to human applications including muscle-wasting disorders such as sarcopenia, or other conditions of limited mobility.

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Exosomal miR-199a-5p promotes hepatic lipid accumulation by modulating MST1 expression and fatty acid metabolism

Cited by 44 publications

References 50 publications

MicroRNAs in the Pathogenesis of Nonalcoholic Fatty Liver Disease

MicroRNAs in the Pathogenesis of Nonalcoholic Fatty Liver Disease

Exosomal microRNAs as diagnostic and therapeutic biomarkers in non-malignant liver diseases

Muscles in Winter: The Epigenetics of Metabolic Arrest

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