Cited by 1,481Cholesterol and Lipid MetabolismAtherosclerosis and Cardiovascular DiseasesLipoproteins and Cardiovascular Health

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Thematic review series: The Pathogenesis of Atherosclerosis. Effects of infection and inflammation on lipid and lipoprotein metabolism mechanisms and consequences to the host

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Khovidhunkit, Weerapan, Kim, Min-Sun, Memon, Riaz A., Shigenaga, Judy K., Moser, Arthur H., Feingold, Kenneth R., Grunfeld, Carl·2004·Journal of Lipid Research

DOI 10.1194/jlr.r300019-jlr200

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Abstract

Infection and inflammation induce the acute-phase response (APR), leading to multiple alterations in lipid and lipoprotein metabolism. Plasma triglyceride levels increase from increased VLDL secretion as a result of adipose tissue lipolysis, increased de novo hepatic fatty acid synthesis, and suppression of fatty acid oxidation. With more severe infection, VLDL clearance decreases secondary to decreased lipoprotein lipase and apolipoprotein E in VLDL. In rodents, hypercholesterolemia occurs attributable to increased hepatic cholesterol synthesis and decreased LDL clearance, conversion of cholesterol to bile acids, and secretion of cholesterol into the bile. Marked alterations in proteins important in HDL metabolism lead to decreased reverse cholesterol transport and increased cholesterol delivery to immune cells. Oxidation of LDL and VLDL increases, whereas HDL becomes a proinflammatory molecule. Lipoproteins become enriched in ceramide, glucosylceramide, and sphingomyelin, enhancing uptake by macrophages. Thus, many of the changes in lipoproteins are proatherogenic. The molecular mechanisms underlying the decrease in many of the proteins during the APR involve coordinated decreases in several nuclear hormone receptors, including peroxisome proliferator-activated receptor, liver X receptor, farnesoid X receptor, and retinoid X receptor. APR-induced alterations initially protect the host from the harmful effects of bacteria, viruses, and parasites. However, if prolonged, these changes in the structure and function of lipoproteins will contribute to atherogenesis.

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Authors: Khovidhunkit, W., Kim, M.-S., Memon, R. A., Shigenaga, J. K., Moser, A. H., Feingold, K. R., & Grunfeld, C.
Affiliations: Chulalongkorn University (TH)
San Francisco VA Medical Center (US)
Corresponding author: Feingold, Kenneth R.
ORCID: Khovidhunkit, Weerapan
Memon, Riaz A.
Venue: Journal of Lipid Research
Publisher: Elsevier BV
Published: 2004-07
Volume: 45
Issue: 7
Pages: 1169-1196
ISSN: 0022-2275 (ISSN-L)
DOI: 10.1194/jlr.r300019-jlr200
OpenAlex: W2340325420
Cited by: 1,481
References: 388
Citations by year: 2026: 61 · 2025: 66 · 2024: 68 · 2023: 79 · 2022: 88 · 2021: 90 · 2020: 72 · 2019: 76 · 2018: 73 · 2017: 76 · 2016: 55 · 2015: 54 · 2014: 74 · 2013: 74 · 2012: 72
FWCI: 9.80
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, 5900 d)
Locations: Journal of Lipid Research (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Greater South Information System
Funders: National Institute of Diabetes and Digestive and Kidney Diseases (DK66999, R01DK066999, DK-49900)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
Keywords: atherogenesis, acute phase response, infection, inflammation, lipid metabolism, lipoprotein metabolism, triglycerides, VLDL secretion, hepatic fatty acid synthesis, lipoprotein lipase, apolipoprotein E, hypercholesterolemia, hepatic cholesterol synthesis, LDL clearance, HDL metabolism, reverse cholesterol transport, LDL oxidation, ceramide, sphingomyelin, macrophage uptake, nuclear receptors, peroxisome proliferator-activated receptors, liver X receptor, farnesoid X receptor, retinoid X receptor, proatherogenic lipoproteins
MeSH terms: Animals, Humans, Immunity, Innate, Infections, Inflammation, Lipids, Lipoproteins, Receptors, Cytoplasmic and Nuclear, Lipid Metabolism

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Thematic review series: The Pathogenesis of Atherosclerosis. Effects of infection and inflammation on lipid and lipoprotein metabolism mechanisms and consequences to the host

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