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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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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