Dataset Information

The role of metabolic lipases in the pathogenesis and management of liver disease.

ABSTRACT: Intracellular lipolysis is an enzymatic pathway responsible for the catabolism of triglycerides (TGs) that is complemented by lipophagy as autophagic breakdown of lipid droplets. The hydrolytic cleavage of TGs generates free fatty acids (FFAs), which can serve as energy substrates, precursors for lipid synthesis and mediators in cell signaling. Despite the fundamental and physiological importance of FFAs, an oversupply can trigger lipotoxicity with impaired membrane function, ER stress, mitochondrial dysfunction, cell death and inflammation. Conversely, impaired release of FFAs and other lipid mediators can also disrupt key cellular signaling functions that regulate metabolism and inflammatory processes. This review will focus on specific functions of intracellular lipases in lipid partitioning, covering basic and translational findings in the context of liver disease. In addition, the clinical relevance of genetic mutations in human disease and potential novel therapeutic opportunities will be discussed.

SUBMITTER: Tardelli M

PROVIDER: S-EPMC7590081 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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The Role of Metabolic Lipases in the Pathogenesis and Management of Liver Disease.

Tardelli Matteo M Bruschi Francesca Virginia FV Trauner Michael M

Hepatology (Baltimore, Md.) 20200901 3

Intracellular lipolysis is an enzymatic pathway responsible for the catabolism of triglycerides (TGs) that is complemented by lipophagy as the autophagic breakdown of lipid droplets. The hydrolytic cleavage of TGs generates free fatty acids (FFAs), which can serve as energy substrates, precursors for lipid synthesis, and mediators in cell signaling. Despite the fundamental and physiological importance of FFAs, an oversupply can trigger lipotoxicity with impaired membrane function, endoplasmic re ...[more]

PMID: 32236963

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Project description:The prevalence of Metabolic-associated fatty liver disease (MAFLD) has been steadily increasing worldwide, paralleling the global epidemic of obesity and diabetes. It is estimated that approximately one-quarter of the global population is affected by MAFLD. Despite its high prevalence, MAFLD often goes undiagnosed due to the lack of specific symptoms in its early stages. However, as the disease progresses, it can lead to more severe liver-related complications such as fibrosis, cirrhosis, and hepatocellular carcinoma. Therefore, we aimed to investigate the expression levels of the nucleotide-binding oligomerization domain, leucine-rich repeat (LRR)-containing proteins (NLR) family pyrin domain-containing protein 3 [NLRP3] inflammasome pathway components, NLRP3 and interleukin 1β (IL-1β) genes in patients with MAFLD with various degrees of steatosis and fibrosis. Participants were classified into two equal groups; MAFLD group: consisted of 120 patients with different degrees of hepatic fibrosis and steatosis based on fibro scan results. The non-MAFLD group was comprised of 107 participants. Molecular analysis of pyrin domain-containing protein 3 and IL-1β relative gene expressions was performed in the blood of all participants, using Real-time quantitative polymerase chain reaction (RT-qPCR). Patients with post-MAFLD hepatic fibrosis had significantly higher relative gene expression levels of IL-1β and NLRP3; with IL-1β > 1.1 had AUC of 0.919, sensitivity of 88.33, specificity of 96.26, PPV of 96.4, and NPV of 88 and 92.3 accuracy (p value < 0.001). NLRP3 > 1.33 had a sensitivity of 97.5, specificity of 99.07, PPV of 99.2, NPV of 97.2, and 98.3 accuracy with an AUC of 0.991 (p value < 0.001) as predictors of post-MAFLD hepatic fibrosis.. A significant increase in the mean relative gene expression levels of both IL-1β and NLRP3 found in patients with early fibrosis (F0-F1-2); 31.97 ± 11.8 and 6.76 ± 2.18, respectively; compared with patients with advanced hepatic fibrosis stages (F2-F3); 2.62 ± 3.71 and 4.27 ± 2.99 (p < 0.001 each). The present study provides novel evidence for the possible involvement of IL-1β and NLRP3 inflammasome in metabolic-associated fatty liver disease pathogenesis and could be valid markers for the early detection of post-MAFLD hepatic fibrosis.

Dataset Information

The role of metabolic lipases in the pathogenesis and management of liver disease.

Publications

The Role of Metabolic Lipases in the Pathogenesis and Management of Liver Disease.

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