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

被引:26
作者
Das, Suman K. [1 ]
Stadelmeyer, Elke [1 ]
Schauer, Silvia [1 ]
Schwarz, Anna [1 ]
Strohmaier, Heimo [2 ]
Claudel, Thiery [3 ]
Zechner, Rudolf [4 ]
Hoefler, Gerald [1 ]
Vesely, Paul W. [1 ,4 ]
机构
[1] Med Univ Graz, Inst Pathol, A-8036 Graz, Austria
[2] Med Univ Graz, Med Res Ctr, A-8010 Graz, Austria
[3] Med Univ Vienna, Div Gastroenterol & Hepatol, Dept Internal Med 3, Hans Popper Lab Mol Hepatol, A-1090 Vienna, Austria
[4] Karl Franzens Univ Graz, Inst Mol Biosci, A-8010 Graz, Austria
基金
欧洲研究理事会;
关键词
miR-124a; metabolism; lipolysis; ATGL; CGI-58; HORMONE-SENSITIVE LIPASE; LIPID STORAGE DISEASE; TISSUE; MACROPHAGES; DEFICIENCY; CATABOLISM; MIR-124; CGI-58; TARGET; GROWTH;
D O I
10.3390/ijms16048555
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:8555 / 8568
页数:14
相关论文
共 26 条
[1]   Lipolysis in adipocytes [J].
Ahmadian, Maryam ;
Wang, Yuhui ;
Sul, Hei Sook .
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2010, 42 (05) :555-559
[2]   Null Mutation in Hormone-Sensitive Lipase Gene and Risk of Type 2 Diabetes [J].
Albert, Jessica S. ;
Yerges-Armstrong, Laura M. ;
Horenstein, Richard B. ;
Pollin, Toni I. ;
Sreenivasan, Urmila T. ;
Chai, Sumbul ;
Blaner, William S. ;
Snitker, Soren ;
O'Connell, Jeffrey R. ;
Gong, Da-Wei ;
Breyer, Richard J., III ;
Ryan, Alice S. ;
McLenithan, John C. ;
Shuldiner, Alan R. ;
Sztalryd, Carole ;
Damcott, Coleen M. .
NEW ENGLAND JOURNAL OF MEDICINE, 2014, 370 (24) :2307-2315
[3]   Cholesteryl ester hydrolase activity is abolished in HSL-/- macrophages but unchanged in macrophages lacking KIAA1363 [J].
Buchebner, Marlene ;
Pfeifer, Thomas ;
Rathke, Nora ;
Chandak, Prakash G. ;
Lass, Achim ;
Schreiber, Renate ;
Kratzer, Adelheid ;
Zimmermann, Robert ;
Sattler, Wolfgang ;
Koefeler, Harald ;
Froehlich, Eleonore ;
Kostner, Gerhard M. ;
Birner-Gruenberger, Ruth ;
Chiang, Kyle P. ;
Haemmerle, Guenter ;
Zechner, Rudolf ;
Levak-Frank, Sanja ;
Cravatt, Benjamin ;
Kratky, Dagmar .
JOURNAL OF LIPID RESEARCH, 2010, 51 (10) :2896-2908
[4]   Adipose Triglyceride Lipase: A New Target in the Regulation of Lipolysis by Insulin [J].
Chakrabarti, Partha ;
Kandror, Konstantin V. .
CURRENT DIABETES REVIEWS, 2011, 7 (04) :270-277
[5]   Adipose Triglyceride Lipase Contributes to Cancer-Associated Cachexia [J].
Das, Suman K. ;
Eder, Sandra ;
Schauer, Silvia ;
Diwoky, Clemens ;
Temmel, Hannes ;
Guertl, Barbara ;
Gorkiewicz, Gregor ;
Tamilarasan, Kuppusamy P. ;
Kumari, Pooja ;
Trauner, Michael ;
Zimmermann, Robert ;
Vesely, Paul ;
Haemmerle, Guenter ;
Zechner, Rudolf ;
Hoefler, Gerald .
SCIENCE, 2011, 333 (6039) :233-238
[6]   Primary adipocyte culture: Adipocyte purification methods may lead to a new understanding of adipose tissue growth and development [J].
Fernyhough, ME ;
Vierck, JL ;
Hausman, GJ ;
Mir, PS ;
Okine, EK ;
Dodson, MV .
CYTOTECHNOLOGY, 2004, 46 (2-3) :163-172
[7]   The gene encoding adipose triglyceride lipase (PNPLA2) is mutated in neutral lipid storage disease with myopathy [J].
Fischer, Judith ;
Lefevre, Caroline ;
Morava, Eva ;
Mussini, Jean-Marie ;
Laforet, Pascal ;
Negre-Salvayre, Anne ;
Lathrop, Mark ;
Salvayre, Robert .
NATURE GENETICS, 2007, 39 (01) :28-30
[8]   Hormone-sensitive lipase deficiency in mice changes the plasma lipid profile by affecting the tissue-specific expression pattern of lipoprotein lipase in adipose tissue and muscle [J].
Haemmerle, G ;
Zimmermann, R ;
Strauss, JG ;
Kratky, D ;
Riederer, M ;
Knipping, G ;
Zechner, R .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (15) :12946-12952
[9]   Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase [J].
Haemmerle, G ;
Lass, A ;
Zimmermann, R ;
Gorkiewicz, G ;
Meyer, C ;
Rozman, J ;
Heldmaier, G ;
Maier, R ;
Theussl, C ;
Eder, S ;
Kratky, D ;
Wagner, EF ;
Klingenspor, M ;
Hoefler, G ;
Zechner, R .
SCIENCE, 2006, 312 (5774) :734-737
[10]   RNAhybrid:: microRNA target prediction easy, fast and flexible [J].
Krueger, Jan ;
Rehmsmeier, Marc .
NUCLEIC ACIDS RESEARCH, 2006, 34 :W451-W454