Cited by 133Lipid metabolism and biosynthesisImmune Response and InflammationLipid metabolism and disorders

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Toll-like Receptor Agonists Promote Prolonged Triglyceride Storage in Macrophages

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Huang, Ying-ling, Morales-Rosado, Joel, Ray, Jessica, Myers, Timothy G., Kho, Terry, Lu, Mingfang, Munford, Robert S.·2014·Journal of Biological Chemistry

DOI 10.1074/jbc.m113.524587PMC PMC3908431

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Abstract

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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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.
ORCID: Myers, Timothy G.
Lu, Mingfang
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 2014-01
Volume: 289
Issue: 5
Pages: 3001-3012
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.m113.524587
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: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 2471 d)
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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Toll-like Receptor Agonists Promote Prolonged Triglyceride Storage in Macrophages

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