title: Micro RNA-124a regulates lipolysis via adipose triglyceride lipase and comparative gene identification 58.
abstract: Lipolysis is the biochemical pathway responsible for the catabolism of cellular triacylglycerol (TG). Lipolytic TG breakdown is a central metabolic process leading to the generation of free fatty acids (FA) and glycerol, thereby regulating lipid, as well as energy homeostasis. The precise tuning of lipolysis is imperative to prevent lipotoxicity, obesity, diabetes and other related metabolic disorders. Here, we present our finding that miR-124a attenuates RNA and protein expression of the major TG hydrolase, adipose triglyceride lipase (ATGL/PNPLA2) and its co-activator comparative gene identification 58 (CGI-58/ABHD5). Ectopic expression of miR-124a in adipocytes leads to reduced lipolysis and increased cellular TG accumulation. This phenotype, however, can be rescued by overexpression of truncated Atgl lacking its 3'UTR, which harbors the identified miR-124a target site. In addition, we observe a strong negative correlation between miR-124a and Atgl expression in various murine tissues. Moreover, miR-124a regulates the expression of Atgl and Cgi-58 in murine white adipose tissue during fasting as well as the expression of Atgl in murine liver, during fasting and re-feeding. Together, these results point to an instrumental role of miR-124a in the regulation of TG catabolism. Therefore, we suggest that miR-124a may be involved in the regulation of several cellular and organismal metabolic parameters, including lipid storage and plasma FA concentration.
authors.affiliation: Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria. paramount.suman@gmail.com.
authors.forename: Suman K
authors.initials: SK
authors.lastname: Das
authors.affiliation: Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria. elke.stadelmeyer@medunigraz.at.
authors.forename: Elke
authors.initials: E
authors.lastname: Stadelmeyer
authors.affiliation: Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria. silvia.schauer@medunigraz.at.
authors.forename: Silvia
authors.initials: S
authors.lastname: Schauer
authors.affiliation: Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria. anna.schwarz@medunigraz.at.
authors.forename: Anna
authors.initials: A
authors.lastname: Schwarz
authors.affiliation: Center for Medical Research, Medical University of Graz, Stiftingtalstrasse 24, 8010 Graz, Austria. heimo.strohmaier@medunigraz.at.
authors.forename: Heimo
authors.initials: H
authors.lastname: Strohmaier
authors.affiliation: Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria. thierry.claudel@meduniwien.ac.at.
authors.forename: Thiery
authors.initials: T
authors.lastname: Claudel
authors.affiliation: Institute of Molecular Biosciences, Karl Franzens University of Graz, Heinrichstraße 31, 8010 Graz, Austria. rudolf.zechner@uni-graz.at.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Zechner
authors.affiliation: Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria. gerald.hoefler@medunigraz.at.
authors.forename: Gerald
authors.initials: G
authors.lastname: Hoefler
authors.affiliation: Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria. paul.vesely@klinikum-graz.at.|Institute of Molecular Biosciences, Karl Franzens University of Graz, Heinrichstraße 31, 8010 Graz, Austria. paul.vesely@klinikum-graz.at.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Vesely
mesh_terms: D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase / Q000096:biosynthesis / Q000235:genetics*; D020413:3' Untranslated Regions; D000818:Animals; D015971:Gene Expression Regulation, Enzymologic; D006367:HeLa Cells; D006801:Humans; D008049:Lipase / Q000096:biosynthesis / Q000235:genetics*; D008066:Lipolysis; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D034622:RNA Interference; D000217:Acyltransferases
chemical_list: D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase; D020413:3' Untranslated Regions; D008049:Lipase; D035683:MicroRNAs; C540079:Mirn124 microRNA, mouse; C492986:Abhd5 protein, mouse; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases