Reduced lysosomal acid lipase activity: A new marker of liver disease severity across the clinical continuum of non-alcoholic fatty liver disease?

Baratta, Francesco; Pastori, Daniele; Ferro, Domenico; Carluccio, Giovanna; Tozzi, Giulia; Angelico, Francesco; Violi, Francesco; Ben, Maria Del

doi:10.3748/wjg.v25.i30.4172

Cited by 30 publications

(8 citation statements)

References 38 publications

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“…The finding of this study suggested a strong association between impaired LAL activity and fatty liver disease. This correlation was confirmed by subsequent studies and may provide new insights into the pathogenesis and progression of NAFLD …”

Section: Endo‐lysosomal Dysfunction In Nafldsupporting

confidence: 62%

“…[43][44][45] Tm6sf2 is a multipass membrane protein localized to the ER and ER-Golgi intermediate compartment. 46 Both the L156P and TA B L E 1 Cellular endo-lysosomal dysfunction in the pathogenesis of NAF LD There is a strong association between impaired LAL activity and NAFLD, but lacking mechanisms [95][96][97][98][99][100] Abbreviations: ABCA1, ATP binding cassette subfamily A member 1; apoB, apolipo-protein B; aSMase, acid sphingomyelinase; CCC, COMMD/ CCDC22/CCDC93; CE, cholesterol ester; CES1, carboxylesterase 1; EE, early endosome; EM, endosomal membrane; ER, endoplasmic reticulum; GLUT4, glucose transporter 4; GWAS, genome-wide association studies; HFD, high fat diet; LAL, lysosomal acid lipase. ; LD, lipid droplet; LDL, low density lipoprotein; LE, late endosome; LY, lysosome; MVB, multivesicular bodies; Npc1, Niemann-Pick C1; Npc2, Niemann-Pick C2; PI3K, phosphoinositide 3-kinases; PM, plasma membrane; Rab, Ras small GTP-binding proteins; TG, triacylglycerols; TLRs, toll-like receptors; Tm6sf2, transmembrane 6 superfamily member 2; Tmbiml, transmembrane BAX inhibitor motif containing 1; TPCs, two-pore channels; WASH, Wiskott-Aldrich syndrome protein and SCAR homologue.…”

Section: Endo -Lysosomal Dys Fun C Ti On In Nafldmentioning

confidence: 99%

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Cellular endo‐lysosomal dysfunction in the pathogenesis of non‐alcoholic fatty liver disease

Qiao

et al. 2019

Liver International

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Non‐alcoholic fatty liver disease (NAFLD), an increasingly devastating human disorder, is characterized by intrahepatic fat accumulation. Although important progress has been made in understanding NAFLD, the fundamental mechanisms involved in the pathogenesis of NAFLD have not been fully explained. The endo‐lysosomal trafficking network is central to lipid metabolism, protein degradation and signal transduction, which are involved in a variety of diseases. In recent years, many genes and pathways in the endo‐lysosomal trafficking network and involved in lysosomal biogenesis have been associated with the development and progression of NAFLD. Mutations of these genes and impaired signalling lead to dysfunction in multiple steps of the endo‐lysosomal network (endocytic trafficking, membrane fusion and lysosomal degradation), resulting in the accumulation of pathogenic proteins. In this review, we will focus on how alterations in these genes and pathways affect endo‐lysosomal trafficking as well as the pathophysiology of NAFLD.

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Section: Endo‐lysosomal Dysfunction In Nafldsupporting

confidence: 62%

Section: Endo -Lysosomal Dys Fun C Ti On In Nafldmentioning

confidence: 99%

Cellular endo‐lysosomal dysfunction in the pathogenesis of non‐alcoholic fatty liver disease

Qiao

et al. 2019

Liver International

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“…PEs may contribute to driving the suppression of inflammatory responses in human cells by a medically and globally important dengue fever virus [32]. Low total ChE can usually be caused by liver damage, such as viral hepatitis, liver cirrhosis, and liver cancer [33]. Therefore, the dramatic reduction of such lipids was also consistent with the hepatic impairment associated with COVID-19, especially for patients in the SE group.…”

Section: Discussionmentioning

confidence: 90%

Lipidomic alteration of plasma in cured COVID-19 patients using ultra high-performance liquid chromatography with high-resolution mass spectrometry

Bai¹,

Huang²,

Li³

et al. 2021

Bioscience Reports

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Background: The pandemic of novel coronavirus disease 2019 (COVID-19) has become a serious public health crisis worldwide. The symptoms of COVID-19 vary from mild to severe among different age groups, but the physiological changes related to COVID-19 are barely understood. Methods: In this study, a high-resolution mass spectrometry (HRMS)-based lipidomic strategy was used to characterize the endogenous plasma lipids for cured COVID-19 patients with different ages and symptoms. These patients were further divided into two groups: those with severe symptoms or who were elderly and relatively young patients with mild symptoms. In addition, automated lipidomic identification and alignment was conducted by LipidSearch software. Multivariate and univariate analyses were used for differential comparison. Results: Nearly 500 lipid compounds were identified in each cured COVID-19 group through LipidSearch software. At the level of lipid subclasses, patients with severe symptoms or elderly patients displayed dramatic changes in plasma lipidomic alterations, such as increased triglycerides and decreased cholesteryl esters. Some of these differential lipids might also have essential biological functions. Furthermore, the differential analysis of plasma lipids among groups was performed to provide potential prognostic indicators, and the change in signaling pathways. Conclusions: Dyslipidemia was observed in cured COVID-19 patients due to the viral infection and medical treatment, and the discharged patients should continue to do consolidation therapy. This work provides valuable knowledge about plasma lipid markers and potential therapeutic targets of COVID-19 and essential resources for further research on the pathogenesis of COVID-19.

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“…Lysosomal acid lipase (LAL) deficiency is observed in two recessive genetic disorders involving increased lysosomal cholesterol ester storage. LAL activity was shown to be significantly reduced in children [43] and adults [44,45] with NAFLD, suggesting a possible role of LAL reduction in the progression of NAFLD [46]. It is not yet known whether the presence of these polymorphisms modify the response to lifestyle or pharmacological interventions designed to slow or reverse the development and progression of NAFLD.…”

Section: Clinical Pathophysiologymentioning

confidence: 99%

Pediatric Non-Alcoholic Fatty Liver Disease: Nutritional Origins and Potential Molecular Mechanisms

et al. 2020

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Non-alcoholic fatty liver disease (NAFLD) is the number one chronic liver disease worldwide and is estimated to affect nearly 40% of obese youth and up to 10% of the general pediatric population without any obvious signs or symptoms. Although the early stages of NAFLD are reversible with diet and lifestyle modifications, detecting such stages is hindered by a lack of non-invasive methods of risk assessment and diagnosis. This absence of non-invasive means of diagnosis is directly related to the scarcity of long-term prospective studies of pediatric NAFLD in children and adolescents. In the majority of pediatric NAFLD cases, the mechanisms driving the origin and rapid progression of NAFLD remain unknown. The progression from NAFLD to non-alcoholic steatohepatitis (NASH) in youth is associated with unique histological features and possible immune processes and metabolic pathways that may reflect different mechanisms compared with adults. Recent data suggest that circulating microRNAs (miRNAs) are important new biomarkers underlying pathways of liver injury. Several factors may contribute to pediatric NAFLD development, including high-sugar diets, in utero exposures via epigenetic alterations, changes in the neonatal microbiome, and altered immune system development and mitochondrial function. This review focuses on the unique aspects of pediatric NAFLD and how nutritional exposures impact the immune system, mitochondria, and liver/gastrointestinal metabolic health. These factors highlight the need for answers to how NAFLD develops in children and for early stage-specific interventions.

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Reduced lysosomal acid lipase activity: A new marker of liver disease severity across the clinical continuum of non-alcoholic fatty liver disease?

Cited by 30 publications

References 38 publications

Cellular endo‐lysosomal dysfunction in the pathogenesis of non‐alcoholic fatty liver disease

Cellular endo‐lysosomal dysfunction in the pathogenesis of non‐alcoholic fatty liver disease

Lipidomic alteration of plasma in cured COVID-19 patients using ultra high-performance liquid chromatography with high-resolution mass spectrometry

Pediatric Non-Alcoholic Fatty Liver Disease: Nutritional Origins and Potential Molecular Mechanisms

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