Micro RNA-124a Regulates Lipolysis via Adipose Triglyceride Lipase and Comparative Gene Identification 58
| Autor: | Anna Schwarz, Paul Vesely, Silvia Schauer, Elke Stadelmeyer, Rudolf Zechner, Heimo Strohmaier, Gerald Hoefler, Thiery Claudel, Suman K. Das |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
White adipose tissue
Biology Gene Expression Regulation Enzymologic Article Catalysis Inorganic Chemistry lcsh:Chemistry Mice ATGL microRNA Animals Humans Lipolysis Physical and Theoretical Chemistry 3' Untranslated Regions Molecular Biology lcsh:QH301-705.5 Spectroscopy Regulation of gene expression CGI-58 Catabolism Organic Chemistry Lipase General Medicine 1-Acylglycerol-3-Phosphate O-Acyltransferase Computer Science Applications miR-124a MicroRNAs Lipotoxicity Biochemistry lcsh:Biology (General) lcsh:QD1-999 Adipose triglyceride lipase lipolysis RNA Interference Ectopic expression metabolism HeLa Cells |
| Zdroj: | International Journal of Molecular Sciences, Vol 16, Iss 4, Pp 8555-8568 (2015) International Journal of Molecular Sciences Volume 16 Issue 4 Pages 8555-8568 |
| ISSN: | 1422-0067 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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