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Toll-like Receptor Agonists Promote Prolonged Triglyceride Storage in Macrophages
Open accessAbstract
Macrophages in infected tissues may sense microbial molecules that significantly alter their metabolism. In a seeming paradox, these critical host defense cells often respond by increasing glucose catabolism while simultaneously storing fatty acids (FA) as triglycerides (TAG) in lipid droplets. We used a load-chase strategy to study the mechanisms that promote long term retention of TAG in murine and human macrophages. Toll-like receptor (TLR)1/2, TLR3, and TLR4 agonists all induced the cells to retain TAG for ≥3 days. Prolonged TAG retention was accompanied by the following: (a) enhanced FA uptake and FA incorporation into TAG, with long lasting increases in acyl-CoA synthetase long 1 (ACSL1) and diacylglycerol acyltransferase-2 (DGAT2), and (b) decreases in lipolysis and FA β-oxidation that paralleled a prolonged drop in adipose triglyceride lipase (ATGL). TLR agonist-induced TAG storage is a multifaceted process that persists long after most early pro-inflammatory responses have subsided and may contribute to the formation of "lipid-laden" macrophages in infected tissues.
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“LDs form in myeloid cells through the upregulation of lipid-synthesis enzymes triggered by the engagement of toll receptors by innate immune triggers, such as bacteria7.”
From APOE4/4 is linked to damaging lipid droplets in Alzheimer’s disease microglia (2024) · cites this paper as [7]
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Cites
Toll-like receptor–induced changes in glycolytic metabolism regulate dendritic cell activation
Krawczyk, C. M., Holowka, T., Sun, J., Blagih, J., Amiel, E., DeBerardinis, R. J., Cross, J. R., Jung, E., Thompson, C. B., Jones, R. G., et al. (2010) · Blood · doi:10.1182/blood-2009-10-249540 · Cited by 1,246
Systems biology approaches identify ATF3 as a negative regulator of Toll-like receptor 4
Gilchrist, M., Thórsson, V., Li, B., Rust, A. G., Korb, M., Kennedy, K., Hai, T., Bolouri, H., & Aderem, A. A. (2006) · Nature · doi:10.1038/nature04768 · Cited by 810
Two physically, functionally, and developmentally distinct peritoneal macrophage subsets
Ghosn, E. E. B., Cassado, A. A., Govoni, G. R., Fukuhara, T., Yang, Y., Monack, D. M., Bortoluci, K. R., Almeida, S. R., Herzenberg, L. A., & Herzenberg, L. A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0915000107 · Cited by 689
Spann, N. J., Garmire, L. X., McDonald, J. G., Myers, D. S., Milne, S. B., Shibata, N., Reichart, D. R., Fox, J. N., Shaked, I., Heudobler, D., et al. (2012) · Cell · doi:10.1016/j.cell.2012.06.054 · Cited by 630
Caseation of human tuberculosis granulomas correlates with elevated host lipid metabolism
Kim, M., Wainwright, H. C., Locketz, M., Bekker, L., Walther, G. B., Dittrich, C., Visser, A., Wang, W., Hsu, F., Wiehart, U., et al. (2010) · EMBO Molecular Medicine · doi:10.1002/emmm.201000079 · Cited by 489
Mammalian Long-Chain Acyl-CoA Synthetases
Soupène, E., & Kuypers, F. A. (2008) · Experimental Biology and Medicine · doi:10.3181/0710-mr-287 · Cited by 465
Metabolism of glucose, glutamine, long-chain fatty acids and ketone bodies by murine macrophages
Newsholme, P., Curi, R., Gordon, S., & Newsholme, E. A. (1986) · Biochemical Journal · doi:10.1042/bj2390121 · Cited by 424
Glycerolipid Metabolism and Signaling in Health and Disease
Prentki, M., & Madiraju, S. R. M. (2008) · Endocrine Reviews · doi:10.1210/er.2008-0007 · Cited by 331
Kanter, J. E., Kramer, F., Barnhart, S., Averill, M. M., Vivekanandan‐Giri, A., Vickery, T. W., Li, L. O., Becker, L., Yuan, W., Chait, A., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1111600109 · Cited by 314
Newsholme, P., Gordon, S. B., & Newsholme, E. A. (1987) · Biochemical Journal · doi:10.1042/bj2420631 · Cited by 311
D’Avila, H., Melo, R. C. N., Parreira, G. G., Werneck-Barroso, E., Castro-Faria-Neto, H. C., & Bozza, P. T. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.5.3087 · Cited by 289
Mechanisms of triglyceride accumulation in activated macrophages
Feingold, K. R., Shigenaga, J. K., Kazemi, M. R., McDonald, C. M., Patzek, S. M., Cross, A. S., Moser, A. H., & Grünfeld, C. (2012) · Journal of Leukocyte Biology · doi:10.1189/jlb.1111537 · Cited by 257
Leukocyte lipid bodies — Biogenesis and functions in inflammation
Bozza, P. T., Magalhães, K. G., & Weller, P. F. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2009.01.005 · Cited by 248
Acyl-CoA synthesis, lipid metabolism and lipotoxicity
Li, L. O., Klett, E. L., & Coleman, R. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2009.09.024 · Cited by 244
Substrate cycles in metabolic regulation and in heat generation.
Newsholme, E. A., & Crabtree, B. (1976) · PubMed · Cited by 236
DeBerardinis, R. J., Lum, J. J., & Thompson, C. B. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m608372200 · Cited by 221
Newsholme, P., & Newsholme, E. A. (1989) · Biochemical Journal · doi:10.1042/bj2610211 · Cited by 217
Functional Studies on Native and Mutated Forms of Perilipins
Tansey, J. T., Huml, A. M., Vogt, R. D., Davis, K. E., Jones, J. M., Fraser, K. A., Brasaemle, D., Kimmel, A. R., & Londos, C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m211005200 · Cited by 205
Funk, J. L., Feingold, K. R., Moser, A. H., & Grünfeld, C. (1993) · Atherosclerosis · doi:10.1016/0021-9150(93)90224-i · Cited by 172
Reassessing triglyceride synthesis in adipose tissue
Nye, C. K., Kim, J., Kalhan, S. C., & Hanson, R. W. (2008) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2008.08.003 · Cited by 156
Igal, R. A., WANG, P. H., & Coleman, R. (1997) · Biochemical Journal · doi:10.1042/bj3240529 · Cited by 152
Kazemi, M. R., McDonald, C. M., Shigenaga, J. K., Grünfeld, C., & Feingold, K. R. (2005) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000159163.52632.1b · Cited by 146
Transcriptional network dynamics in macrophage activation
Nilsson, R., Bajić, V. B., Suzuki, H., di Bernardo, D., Björkegren, J., Katayama, S., Reid, J. F., Sweet, M. J., Gariboldi, M., Carninci, P., et al. (2006) · Genomics · doi:10.1016/j.ygeno.2006.03.022 · Cited by 123
Complete Inhibition of Mouse Macrophage-Derived Foam Cell Formation by Triacsin C
Namatame, I., Tomoda, H., Arai, H., Inoue, K., & Omura, S. (1999) · Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a022289 · Cited by 74
Rubinow, K. B., Wall, V., Nelson, J. D., Mar, D., Bomsztyk, K., Askari, B., Lai, M. A., Smith, K. D., Han, M. S., Vivekanandan‐Giri, A., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.458372 · Cited by 67
Nicolaou, G., Goodall, A. H., & Erridge, C. (2011) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.10249 · Cited by 63
Saraswathi, V., & Hasty, A. H. (2009) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.109.195362 · Cited by 53
Maurya, M. R., Gupta, S., Li, X., Fahy, E., Dinasarapu, A. R., Sud, M., Brown, H. A., Glass, C. K., Murphy, R. C., Russell, D. W., et al. (2013) · Journal of Lipid Research · doi:10.1194/jlr.m040212 · Cited by 53
ADRP/ADFP and Mal1 expression are increased in macrophages treated with TLR agonists
Feingold, K. R., Kazemi, M. R., Magra, A. L., McDonald, C. M., Chui, L. G., Shigenaga, J. K., Patzek, S. M., Chan, Z. W., Londos, C., & Grünfeld, C. (2009) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2009.08.042 · Cited by 52
Stimulus-dependent Deacylation of Bacterial Lipopolysaccharide by Dendritic Cells
Lu, M., Zhang, M., Kitchens, R. L., Fosmire, S. P., Takashima, A., & Munford, R. S. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030420 · Cited by 51
Self-citationBiosynthetic radiolabeling of bacterial lipopolysaccharide to high specific activity
Munford, R. S., DeVeaux, L. C., Cronan, J. E., & Rick, P. D. (1992) · Journal of Immunological Methods · doi:10.1016/0022-1759(92)90164-o · Cited by 42
Self-citationLactate transport in macrophages
Loike, J. D., Kaback, E., Silverstein, S. C., & Steinberg, T. H. (1993) · The Journal of Immunology · doi:10.4049/jimmunol.150.5.1951 · Cited by 28
Methods to Monitor Fatty Acid Transport Proceeding Through Vectorial Acylation
Arias‐Barrau, E., Dirusso, C., & Black, P. N. (2009) · Humana Press eBooks · doi:10.1007/978-1-60761-325-1_13 · Cited by 25
Adler‐Wailes, D. C., Guiney, E. L., Wolins, N. E., & Yanovski, J. A. (2010) · Endocrinology · doi:10.1210/en.2009-1364 · Cited by 9
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APOE4/4 is linked to damaging lipid droplets in Alzheimer’s disease microglia
Haney, M. S., Pálovics, R., Munson, C. N., Long, C., Johansson, P. K., Yip, O., Dong, W., Rawat, E., West, E., Schlachetzki, J. C. M., et al. (2024) · Nature · doi:10.1038/s41586-024-07185-7 · Cited by 536
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York, A. G., Williams, K. J., Argus, J. P., Zhou, Q. D., Brar, G., Vergnes, L., Gray, E. E., Zhen, A., Wu, N. C., Yamada, D. H., et al. (2015) · Cell · doi:10.1016/j.cell.2015.11.045 · Cited by 461
Oishi, Y., Spann, N. J., Link, V. M., Muse, E. D., Strid, T., Edillor, C., Kolar, M. J., Matsuzaka, T., Hayakawa, S., Tao, J., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2016.11.009 · Cited by 342
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Garaude, J., Acín-Pérez, R., Martínez-Cano, S., Enamorado, M., Ugolini, M., Nistal-Villán, E., Hervás-Stubbs, S., Pelegrín, P., Sander, L. E., Enríquez, J. A., et al. (2016) · Nature Immunology · doi:10.1038/ni.3509 · Cited by 313
Metadata
- Authors
- Huang, Y.-L., Morales-Rosado, J., Ray, J., Myers, T. G., Kho, T., Lu, M., & Munford, R. S.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Munford, Robert S.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 289
- Issue
- 5
- Pages
- 3001-3012
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3908431
- OpenAlex
- W1997812608
- Cited by
- 133
- References
- 34
- Citations by year
- 2026: 11 · 2025: 13 · 2024: 11 · 2023: 8 · 2022: 10 · 2021: 21 · 2020: 20 · 2019: 8 · 2018: 8 · 2017: 6 · 2016: 9 · 2015: 3 · 2014: 4
- FWCI
- 2.49
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases
- NHLBI Division of Intramural Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- TLR agonists, macrophages, triglyceride storage, lipid droplets, fatty acid uptake, diacylglycerol acyltransferase 2, adipose triglyceride lipase, lipolysis, fatty acid beta-oxidation, TLR1/2, TLR3, TLR4, lipid-laden macrophages, infection
- MeSH terms
- Animals, Cells, Cultured, Coenzyme A Ligases, Fatty Acids, Foam Cells, Humans, Lipolysis, Lipopolysaccharides, Macrophages, Mice, Inbred C57BL, Monocytes, Triglycerides, Mice, Knockout, Diacylglycerol O-Acyltransferase, Toll-Like Receptor 1, Toll-Like Receptor 2, Toll-Like Receptor 3, Toll-Like Receptor 4, Mice
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