Effects of infection and inflammation on lipid and lipoprotein metabolism: mechanisms and consequences to the host.

By W. Khovidhunkit, Min-Sun Kim, R. Memon, J. Shigenaga, A. Moser, K. Feingold, C. Grunfeld. Journal of Lipid Research, 2004

955 citations recorded by the source corpus.

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.

Subfields: Endocrinology, Diabetes and Metabolism, Epidemiology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/9f4181cbf6f9bf8abc43d8d079a402ef31fa6c9f

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Citations in the corpus

Functionally Defective High-Density Lipoprotein: A New Therapeutic Target at the Crossroads of Dyslipidemia, Inflammation, and Atherosclerosis (2006, positive): “Under such conditions, TG typically replace CE in the HDL core, resulting in a low CE/TG ratio and in a decrease in plasma HDL-C levels, another feature of the acute phase response (Khovidhunkit et al., 2004b).”
Norepinephrine and octopamine: linking stress and immune function across phyla (2008, positive): “During infection, VLDL levels increase (Khovidhunkit et al., 2004).”
Increased Infiltration of Macrophages in Omental Adipose Tissue Is Associated With Marked Hepatic Lesions in Morbid Human Obesity (2006, positive): “Activated macrophages secrete numerous cytokines that activate lipolysis through various signaling pathways converging on phosphorylation of hormone-sensitive lipase or its associated proteins, such as perilipins (32).”