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Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
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
Doi: 10.1194/jlr.M052613
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- Führende Autor*innen der Med Uni Graz
- Göritzer Madeleine
- Kratky Dagmar
- Co-Autor*innen der Med Uni Graz
- Chandak Prakash Gopal Das
- Graier Wolfgang
- Kolb Dagmar
- Madreiter-Sokolowski Corina
- Obrowsky Sascha
- Radovic Branislav
- Rainer Silvia
- Sachdev Vinay
- Sattler Wolfgang
- Schlager Stefanie
- Vujic Nemanja
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- Abstract:
- 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)
- inflammation
- lipid droplets
- storage diseases
- comparative gene identification-58