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

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

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

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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Crossref · 10.1194/jlr.r300019-jlr200

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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.
Venue
Journal of Lipid Research
Publisher
Elsevier BV
Published
2004-07
Volume
45
Issue
7
Pages
1169-1196
ISSN
0022-2275 (ISSN-L)
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
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
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Health Sciences › Medicine › Surgery › 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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