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Micro RNA-124a Regulates Lipolysis via Adipose Triglyceride Lipase and Comparative Gene Identification 58
被引:26
作者:

Das, Suman K.
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Med Univ Graz, Inst Pathol, A-8036 Graz, Austria Med Univ Graz, Inst Pathol, A-8036 Graz, Austria

Stadelmeyer, Elke
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Med Univ Graz, Inst Pathol, A-8036 Graz, Austria Med Univ Graz, Inst Pathol, A-8036 Graz, Austria

Schauer, Silvia
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Med Univ Graz, Inst Pathol, A-8036 Graz, Austria Med Univ Graz, Inst Pathol, A-8036 Graz, Austria

Schwarz, Anna
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Med Univ Graz, Inst Pathol, A-8036 Graz, Austria Med Univ Graz, Inst Pathol, A-8036 Graz, Austria

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Claudel, Thiery
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Med Univ Vienna, Div Gastroenterol & Hepatol, Dept Internal Med 3, Hans Popper Lab Mol Hepatol, A-1090 Vienna, Austria Med Univ Graz, Inst Pathol, A-8036 Graz, Austria

Zechner, Rudolf
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机构:
Karl Franzens Univ Graz, Inst Mol Biosci, A-8010 Graz, Austria Med Univ Graz, Inst Pathol, A-8036 Graz, Austria

Hoefler, Gerald
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Med Univ Graz, Inst Pathol, A-8036 Graz, Austria Med Univ Graz, Inst Pathol, A-8036 Graz, Austria

Vesely, Paul W.
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机构:
Med Univ Graz, Inst Pathol, A-8036 Graz, Austria
Karl Franzens Univ Graz, Inst Mol Biosci, A-8010 Graz, Austria Med Univ Graz, Inst Pathol, A-8036 Graz, Austria
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.
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页码:8555 / 8568
页数:14
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Zimmermann, R
;
Gorkiewicz, G
;
Meyer, C
;
Rozman, J
;
Heldmaier, G
;
Maier, R
;
Theussl, C
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Eder, S
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Kratky, D
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Wagner, EF
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SCIENCE,
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Lass, A
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机构: Graz Univ, Inst Mol Biosci, A-8010 Graz, Austria

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Meyer, C
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机构: Graz Univ, Inst Mol Biosci, A-8010 Graz, Austria

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Heldmaier, G
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机构: Graz Univ, Inst Mol Biosci, A-8010 Graz, Austria

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Theussl, C
论文数: 0 引用数: 0
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机构: Graz Univ, Inst Mol Biosci, A-8010 Graz, Austria

Eder, S
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机构: Graz Univ, Inst Mol Biosci, A-8010 Graz, Austria

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Wagner, EF
论文数: 0 引用数: 0
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机构: Graz Univ, Inst Mol Biosci, A-8010 Graz, Austria

Klingenspor, M
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机构: Graz Univ, Inst Mol Biosci, A-8010 Graz, Austria

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Zechner, R
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Graz Univ, Inst Mol Biosci, A-8010 Graz, Austria Graz Univ, Inst Mol Biosci, A-8010 Graz, Austria
[10]
RNAhybrid:: microRNA target prediction easy, fast and flexible
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Krueger, Jan
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Rehmsmeier, Marc
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NUCLEIC ACIDS RESEARCH,
2006, 34
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Krueger, Jan
论文数: 0 引用数: 0
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机构:
Univ Bielefeld, Ctr Biotechnol, CeBiTec, D-33594 Bielefeld, Germany Univ Bielefeld, Ctr Biotechnol, CeBiTec, D-33594 Bielefeld, Germany

Rehmsmeier, Marc
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Univ Bielefeld, Ctr Biotechnol, CeBiTec, D-33594 Bielefeld, Germany Univ Bielefeld, Ctr Biotechnol, CeBiTec, D-33594 Bielefeld, Germany