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Journal of Lipid Research, Vol. 49, 2179-2187, October 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

LPS decreases fatty acid oxidation and nuclear hormone receptors in the kidney^*

Kenneth R. Feingold¹, Yuwei Wang, Arthur Moser, Judy K. Shigenaga and Carl Grunfeld

Metabolism Section, Department of Veterans Affairs Medical Center, San Francisco, CA; and Department of Medicine, University of California, San Francisco, CA

^* This work was supported by grants from the Research Service of the Department of Veterans Affairs and by National Institutes of Health Grant 5 RO1 AR-049932.

Published, JLR Papers in Press, June 23, 2008.

¹ To whom correspondence should be addressed. e-mail: kfngld{at}itsa.ucsf.edu

Inflammation produces marked changes in lipid metabolism, including increased serum fatty acids (FAs) and triglycerides (TGs), increased hepatic TG production and VLDL secretion, increased adipose tissue lipolysis, and decreased FA oxidation in liver and heart. Lipopolysaccharide (LPS) also increases TG and cholesteryl ester levels in kidneys. Here we confirm these findings and define potential mechanisms. LPS decreases renal FA oxidation by 40% and the expression of key proteins required for oxidation of FAs, including FA transport protein-2, fatty acyl-CoA synthase, carnitine palmitoyltransferase-1, medium-chain acyl-CoA dehydrogenase, and acyl-CoA oxidase. Similar decreases were observed in peroxisome proliferator-activated receptor (PPAR)-deficient mice. LPS also caused a reduction in renal mRNA levels of PPAR (75% decrease), thyroid hormone receptor (TR) (92% decrease), and TRβ (84% decrease), whereas PPARβ/ and were not altered. Expression of PGC1 and β, coactivators required for PPARs and TR, was also decreased in kidneys of LPS-treated mice, as were mitochondrial genes regulated by PGC1 (Atp5g1, COX5a, Idh3a, and Ndufs8). Decreased renal FA oxidation could be a by-product of the systemic coordinated host response to increase FAs and TGs available for host defense and/or tissue repair. However, the kidney requires energy to support its transport functions, and the inability to generate energy via FA oxidation might contribute to the renal failure seen in severe sepsis.

Supplementary key words acute phase • infection • inflammation • peroxisome proliferator-activated receptor • PGC1 • thyroid hormone receptor • carnitine palmitoyltransferase 1

Abbreviations: ACO, acyl-CoA oxidase; CPT, carnitine palmitoyltransferase; C_t, cycle of threshold; DGAT, diacylglycerol acyltransferase; FA, fatty acid; FACS, fatty acyl-CoA synthase; FATP, FA transport protein; LPS, lipopolysaccharide; MCAD, medium-chain acyl CoA dehydrogenase; PPAR, peroxisome proliferator-activated receptor; RXR, retinoid X receptor; TG, triglyceride; TR, thyroid hormone receptor

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