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Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

Goeritzer, M; Schlager, S; Radovic, B; Madreiter, CT; Rainer, S; Thomas, G; Lord, CC; Sacks, J; Brown, AL; Vujic, N; Obrowsky, S; Sachdev, V; Kolb, D; Chandak, PG; Graier, WF; Sattler, W; Brown, JM; Kratky, D.
Deletion of CGI-58 or adipose triglyceride lipase differently affects macrophage function and atherosclerosis.
J Lipid Res. 2014; 55(12):2562-2575 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG


Autor/innen der Med Uni Graz:
Chandak Prakash Gopal Das
Göritzer Madeleine
Graier Wolfgang
Kolb-Lenz Dagmar
Kratky Dagmar
Madreiter-Sokolowski Corina
Obrowsky Sascha
Radovic Branislav
Rainer Silvia
Sachdev Vinay
Sattler Wolfgang
Schlager Stefanie
Vujic Nemanja

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Plum Analytics:
Number of Figures: 8
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Cellular TG stores are efficiently hydrolyzed by adipose TG lipase (ATGL). Its coactivator comparative gene identification-58 (CGI-58) strongly increases ATGL-mediated TG catabolism in cell culture experiments. To investigate the consequences of CGI-58 deficiency in murine macrophages, we generated mice with a targeted deletion of CGI-58 in myeloid cells (macCGI-58(-/-) mice). CGI-58(-/-) macrophages accumulate intracellular TG-rich lipid droplets and have decreased phagocytic capacity, comparable to ATGL(-/-) macrophages. In contrast to ATGL(-/-) macrophages, however, CGI-58(-/-) macrophages have intact mitochondria and show no indications of mitochondrial apoptosis and endoplasmic reticulum stress, suggesting that TG accumulation per se lacks a significant role in processes leading to mitochondrial dysfunction. Another notable difference is the fact that CGI-58(-/-) macrophages adopt an M1-like phenotype in vitro. Finally, we investigated atherosclerosis susceptibility in macCGI-58/ApoE-double KO (DKO) animals. In response to high-fat/high-cholesterol diet feeding, DKO animals showed comparable plaque formation as observed in ApoE(-/-) mice. In agreement, antisense oligonucleotide-mediated knockdown of CGI-58 in LDL receptor(-/-) mice did not alter atherosclerosis burden in the aortic root. These results suggest that macrophage function and atherosclerosis susceptibility differ fundamentally in these two animal models with disturbed TG catabolism, showing a more severe phenotype by ATGL deficiency. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.
Find related publications in this database (using NLM MeSH Indexing)
1-Acylglycerol-3-Phosphate O-Acyltransferase - antagonists & inhibitors
1-Acylglycerol-3-Phosphate O-Acyltransferase - genetics
1-Acylglycerol-3-Phosphate O-Acyltransferase - metabolism
Animals -
Apoptosis -
Atherosclerosis - etiology
Atherosclerosis - immunology
Atherosclerosis - metabolism
Atherosclerosis - pathology
Cells, Cultured -
Crosses, Genetic -
Diet, High-Fat - adverse effects
Female -
Gene Deletion -
Gene Knockdown Techniques -
Lipase - genetics
Lipase - metabolism
Lipid Droplets - immunology
Lipid Droplets - metabolism
Lipid Droplets - ultrastructure
Macrophages, Peritoneal - immunology
Macrophages, Peritoneal - metabolism
Macrophages, Peritoneal - ultrastructure
Male -
Mice, Inbred C57BL -
Mice, Knockout -
Mice, Transgenic -
Microscopy, Electron, Transmission -
Mitochondria - immunology
Mitochondria - metabolism
Mitochondria - ultrastructure
Oligonucleotides, Antisense - administration & dosage
Phagocytosis -
Triglycerides - metabolism

Find related publications in this database (Keywords)
lipid droplets
storage diseases
comparative gene identification-58
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