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dc.contributor.author
Quiroga, Ariel Dario
dc.contributor.author
Lehner, Richard
dc.date.available
2019-10-21T17:44:00Z
dc.date.issued
2018-09
dc.identifier.citation
Quiroga, Ariel Dario; Lehner, Richard; Pharmacological intervention of liver triacylglycerol lipolysis: The good, the bad and the ugly; Pergamon-Elsevier Science Ltd; Biochemical Pharmacology; 155; 9-2018; 233-241
dc.identifier.issn
0006-2952
dc.identifier.uri
http://hdl.handle.net/11336/86644
dc.description.abstract
Excessive triacylglycerol (TG) accumulation is the distinctive feature of obesity. In the liver, sustained TG accretion leads to nonalcoholic fatty liver disease (NAFLD), eventually progressing to non-alcoholic steatohepatitis (NASH) and cirrhosis, which is associated with complications including hepatic failure, hepatocellular carcinoma and death. Pharmacological interventions are actively pursued to prevent lipid accumulation in hepatocytes and, therefore, to ameliorate the associated pathophysiological conditions. Here, we sought to provide an overview of the pharmacological approaches to up- or downregulate the expression and activities of the enzymes involved in hepatic TG hydrolysis. Fatty acids (FA) released by hydrolysis of hepatic TG can be used for β-oxidation, signaling, and for very low-density lipoprotein (VLDL)-TG synthesis. Originally, lipolysis was believed to be centered in the adipose and to be catalyzed by only two lipases, hormone-sensitive lipase (HSL) and monoacylglycerol lipase (MAGL). However, genetic ablation of HSL expression in mice failed to erase TG hydrolysis in adipocytes leading to the identification of a third lipase termed adipose triglyceride lipase (ATGL). Although these three enzymes are considered to be the main players governing lipolysis in the adipocyte, other lipolytic enzymes have been described to contribute to hepatic TG metabolism. These include adiponutrin/patatin-like phospholipase domain containing 3 (PNPLA3), some members of the carboxylesterase family (CES/Ces), arylacetamide deacetylase (AADAC), lysosomal acid lipase (LAL) and hepatic lipase (HL). This review highlights the consequences of pharmacological interventions of liver lipases that degrade TG in cytosolic lipid droplets, in the endoplasmic reticulum, in the late endosomes/lysosomes and along the secretory route.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Pergamon-Elsevier Science Ltd
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.subject
INHIBITOR
dc.subject
LIPASE
dc.subject
LIPID DROPLETS
dc.subject
LIVER
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TRIACYLGLYCEROL
dc.subject.classification
Fisiología
dc.subject.classification
Medicina Básica
dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Pharmacological intervention of liver triacylglycerol lipolysis: The good, the bad and the ugly
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2019-10-15T13:19:09Z
dc.identifier.eissn
0006-2952
dc.journal.volume
155
dc.journal.pagination
233-241
dc.journal.pais
Estados Unidos
dc.description.fil
Fil: Quiroga, Ariel Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina
dc.description.fil
Fil: Lehner, Richard. University of Alberta; Canadá
dc.journal.title
Biochemical Pharmacology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.bcp.2018.07.005
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0006295218302739
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