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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Goeritzer, Madeleine Schlager, Stefanie Radovic, Branislav Madreiter, Corina T. Rainer, Silvia Thomas, Gwynneth Lord, Caleb C. Sacks, Jessica Brown, Amanda L. Vujic, Nemanja Obrowsky, Sascha Sachdev, Vinay Kolb, Dagmar Chandak, Prakash G. Graier, Wolfgang F. Sattler, Wolfgang Brown, J. Mark Kratky, Dagmar |
| Description | Country affiliation: Austria Author Affiliation: Goeritzer M ( Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Graz, Austria.); Schlager S ( Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Graz, Austria.); Radovic B ( Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Graz, Austria.); Madreiter CT ( Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Graz, Austria.); Rainer S ( Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Graz, Austria.); Thomas G ( Department of Pathology, Section on Lipid Sciences, Wake Forest University School of Medicine, Winston-Salem, NC.); Lord CC ( Division of Hypothalamic Research, University of Texas Southwestern Medical Center, Dallas, TX.); Sacks J ( Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH.); Brown AL ( Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH.); Vujic N ( Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Graz, Austria.); Obrowsky S ( Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Graz, Austria.); Sachdev V ( Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Graz, Austria.); Kolb D ( Center for Medical Research/Institute of Cell Biology, Histology, and Embryology, Medical University of Graz, Graz, Austria.); Chandak PG ( Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Graz, Austria.); Graier WF ( Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Graz, Austria.); Sattler W ( Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Graz, Austria.); Brown JM ( Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH.); Kratky D ( Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Graz, Austria.) |
| 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. |
| File Format | HTM / HTML |
| ISSN | 00222275 |
| e-ISSN | 15397262 |
| DOI | 10.1194/jlr.M052613 |
| Journal | The Journal of Lipid Research |
| Issue Number | 12 |
| Volume Number | 55 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology |
| Publisher Date | 2014-12-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Discipline Biochemistry 1-acylglycerol-3-phosphate O-acyltransferase Metabolism Atherosclerosis Gene Deletion Lipase Macrophages, Peritoneal Immunology Phagocytosis Antagonists & Inhibitors Genetics Animals Apoptosis Etiology Pathology Cells, Cultured Crosses, Genetic Diet, High-fat Adverse Effects Gene Knockdown Techniques Lipid Droplets Ultrastructure Mice, Inbred C57bl Mice, Knockout Mice, Transgenic Microscopy, Electron, Transmission Mitochondria Oligonucleotides, Antisense Administration & Dosage Triglycerides Comparative Study Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Endocrinology |
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