The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
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
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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
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Caseation of human tuberculosis granulomas correlates with elevated host lipid metabolism
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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
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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
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Linking Gut Microbiota and Inflammation to Obesity and Insulin Resistance
Saad, M. J. A., Santos, A., & Prada, P. O. (2016) · Physiology · doi:10.1152/physiol.00041.2015 · Cited by 836
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
“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 bacteria 7 .”
Self-citationLimiting Cholesterol Biosynthetic Flux Spontaneously Engages Type I IFN Signaling
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
Mitochondrial respiratory-chain adaptations in macrophages contribute to antibacterial host defense
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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