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Int. J. Mol. Sci. 2015, 16(4), 8555-8568; doi:10.3390/ijms16048555

Micro RNA-124a Regulates Lipolysis via Adipose Triglyceride Lipase and Comparative Gene Identification 58

1
Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria
2
Center for Medical Research, Medical University of Graz, Stiftingtalstrasse 24, 8010 Graz, Austria
3
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
4
Institute of Molecular Biosciences, Karl Franzens University of Graz, Heinrichstraße 31, 8010 Graz, Austria
*
Authors to whom correspondence should be addressed.
Academic Editor: Martin Pichler
Received: 26 February 2015 / Revised: 24 March 2015 / Accepted: 26 March 2015 / Published: 16 April 2015
(This article belongs to the Collection Regulation by Non-Coding RNAs)
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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. View Full-Text
Keywords: miR-124a; metabolism; lipolysis; ATGL; CGI-58 miR-124a; metabolism; lipolysis; ATGL; CGI-58
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Das, S.K.; Stadelmeyer, E.; Schauer, S.; Schwarz, A.; Strohmaier, H.; Claudel, T.; Zechner, R.; Hoefler, G.; Vesely, P.W. Micro RNA-124a Regulates Lipolysis via Adipose Triglyceride Lipase and Comparative Gene Identification 58. Int. J. Mol. Sci. 2015, 16, 8555-8568.

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