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标题：Infection decreases fatty acid oxidation and nuclear hormone receptors in the diaphragm
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作者：Kenneth R. Feingold ; Arthur Moser ; Sophie M. Patzek 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2009
卷号：50
期号：10
页码：2055-2063
DOI：10.1194/jlr.M800655-JLR200
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Respiratory failure is a major cause of mortality during septic shock and is due in part to decreased ventilatory muscle contraction. Ventilatory muscles have high energy demands; fatty acid (FA) oxidation is an important source of ATP. FA oxidation is regulated by nuclear hormone receptors; studies have shown that the expression of these receptors is decreased in liver, heart, and kidney during sepsis. Here, we demonstrate that lipopolysaccharide (LPS) decreases FA oxidation and the expression of lipoprotein lipase (LPL), FA transport protein 1 (FATP-1), CD36, carnitine palmitoyltransferase beta, medium chain acyl-CoA dehydrogenase (MCAD), and acyl-CoA synthetase, key proteins required for FA uptake and oxidation, in the diaphragm. LPS also decreased mRNA levels of PPARα and β/δ, RXRα, β, and γ, thyroid hormone receptor α and β, and estrogen related receptor alpha (ERRα) and their coactivators PGC-1α, PGC-1β, SRC1, SRC2, Lipin 1, and CBP. Zymosan resulted in similar changes in the diaphragm. Finally, in PPARα deficient mice, baseline CPT-1β and FATP-1 levels were markedly decreased and were not further reduced by LPS suggesting that a decrease in the PPARα signaling pathway plays an important role in inducing some of these changes. The decrease in FA oxidation in the diaphragm may be detrimental, leading to decreased diaphragm contraction and an increased risk of respiratory failure during sepsis.
关键词：acute phase ; thyroid hormone receptor ; carnitine palmitoyltransferase I ; fatty acid transport proteins