LPS decreases fatty acid oxidation and nuclear hormone receptors in the kidney
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 α (PPARα)-deficient mice. LPS also caused a reduction in renal mRNA levels of PPARα (75% decrease), thyroid hormone receptor α (TRα) (92% decrease), and TRβ (84% decrease), whereas PPARβ/δ and γ were not altered. Expression of PGC1 α 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. 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 α (PPARα)-deficient mice. LPS also caused a reduction in renal mRNA levels of PPARα (75% decrease), thyroid hormone receptor α (TRα) (92% decrease), and TRβ (84% decrease), whereas PPARβ/δ and γ were not altered. Expression of PGC1 α 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. Infection and inflammation induce an acute-phase response, which results in increases in specific plasma proteins (positive acute-phase proteins) and decreases in other plasma proteins (negative acute-phase proteins) (1Gabay C. Kushner I. Acute-phase proteins and other systemic responses to inflammation.N. Engl. J. Med. 1999; 340: 448-454Crossref PubMed Scopus (5169) Google Scholar). In addition to changes in plasma protein levels, there are also marked changes in circulating lipid and lipoprotein levels, with characteristic findings of increases in serum-free FAs and triglyceride (TG) levels and decreases in serum HDL levels (2Khovidhunkit W. Kim M.S. Memon R.A. Shigenaga J.K. Moser A.H. Feingold K.R. Grunfeld C. Effects of infection and inflammation on lipid and lipoprotein metabolism: mechanisms and consequences to the host.J. Lipid Res. 2004; 45: 1169-1196Abstract Full Text Full Text PDF PubMed Scopus (1102) Google Scholar). Underlying these changes in serum lipid levels are alterations in lipid metabolism, particularly FA metabolism. In adipose tissue, there is enhanced lipolysis and TG mobilization (3Feingold K.R. Staprans I. Memon R.A. Moser A.H. Shigenaga J.K. Doerrler W. Dinarello C.A. Grunfeld C. Endotoxin rapidly induces changes in lipid metabolism that produce hypertriglyceridemia: low doses stimulate hepatic triglyceride production while high doses inhibit clearance.J. Lipid Res. 1992; 33: 1765-1776Abstract Full Text PDF PubMed Google Scholar, 4Nonogaki K. Moser A.H. Pan X.M. Staprans I. Grunfeld C. Feingold K.R. Lipoteichoic acid stimulates lipolysis and hepatic triglyceride secretion in rats in vivo.J. Lipid Res. 1995; 36: 1987-1995Abstract Full Text PDF PubMed Google Scholar), whereas in the liver and heart, there is a decrease in FA oxidation (5Beylot M. Guiraud M. Grau G. Bouletreau P. Regulation of ketone body flux in septic patients.Am. J. Physiol. 1989; 257: E665-E674PubMed Google Scholar, 6Takeyama N. Itoh Y. Kitazawa Y. Tanaka T. Altered hepatic mitochondrial fatty acid oxidation and ketogenesis in endotoxic rats.Am. J. Physiol. 1990; 259: E498-E505Crossref PubMed Google Scholar, 7Liu M.S. Spitzer J.J. In vitro effects of E. coli endotoxin on fatty acid and lactate oxidation in canine myocardium.Circ. Shock. 1977; 4: 181-190PubMed Google Scholar, 8Wang X. Evans R.D. Effect of endotoxin and platelet-activating factor on lipid oxidation in the rat heart.J. Mol. Cell. Cardiol. 1997; 29: 1915-1926Abstract Full Text PDF PubMed Scopus (17) Google Scholar). In the liver, the decrease in FA oxidation is accompanied by an increase in FA synthesis and the enhanced reesterification of FAs into TG, leading to an increase in VLDL production and secretion (2Khovidhunkit W. Kim M.S. Memon R.A. Shigenaga J.K. Moser A.H. Feingold K.R. Grunfeld C. Effects of infection and inflammation on lipid and lipoprotein metabolism: mechanisms and consequences to the host.J. Lipid Res. 2004; 45: 1169-1196Abstract Full Text Full Text PDF PubMed Scopus (1102) Google Scholar, 3Feingold K.R. Staprans I. Memon R.A. Moser A.H. Shigenaga J.K. Doerrler W. Dinarello C.A. Grunfeld C. Endotoxin rapidly induces changes in lipid metabolism that produce hypertriglyceridemia: low doses stimulate hepatic triglyceride production while high doses inhibit clearance.J. Lipid Res. 1992; 33: 1765-1776Abstract Full Text PDF PubMed Google Scholar). The molecular mechanisms underlying these acute-phase changes in FA and TG metabolism are not fully understood, but recent studies have suggested that decreases in the expression of nuclear hormone receptors, particularly retinoid X receptors (RXRs), peroxisome proliferator-activated receptors (PPARs), and thyroid hormone receptors (TRs) play a key role (2Khovidhunkit W. Kim M.S. Memon R.A. Shigenaga J.K. Moser A.H. Feingold K.R. Grunfeld C. Effects of infection and inflammation on lipid and lipoprotein metabolism: mechanisms and consequences to the host.J. Lipid Res. 2004; 45: 1169-1196Abstract Full Text Full Text PDF PubMed Scopus (1102) Google Scholar, 9Beigneux A.P. Moser A.H. Shigenaga J.K. Grunfeld C. Feingold K.R. The acute phase response is associated with retinoid X receptor repression in rodent liver.J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, A.P. Moser A.H. Shigenaga J.K. Grunfeld C. Feingold K.R. is associated with decreased expression and in J. Physiol. PubMed Scopus Google Scholar). are peroxisome proliferator-activated receptor and receptors are by FAs and stimulate the of specific genes that of FA metabolism proliferator-activated genes to Res. PubMed Scopus Google Scholar). PPARs with and to specific response in the of these PPARα a of genes in FA including carnitine medium-chain and acyl-CoA proliferator-activated genes to Res. PubMed Scopus Google Scholar, K. J. of the peroxisome proliferator-activated receptor in the effects of and fatty acids on Lipid Res. Full Text PDF PubMed Google Scholar). PPARα also the genes that the of FAs, as FA transport proteins and for into the fatty acyl-CoA proliferator-activated genes to Res. PubMed Scopus Google Scholar, K. J. of the peroxisome proliferator-activated receptor in the effects of and fatty acids on Lipid Res. Full Text PDF PubMed Google Scholar). with its role in PPARα is in the with high mitochondrial and as liver, heart, and kidney proliferator-activated genes to Res. PubMed Scopus Google Scholar, K. J. of the peroxisome proliferator-activated receptor in the effects of and fatty acids on Lipid Res. Full Text PDF PubMed Google Scholar). In of TR, nuclear hormone which with retinoid X receptor also stimulates FA oxidation by the expression of J. The metabolism of fatty acids in PubMed Scopus Google Scholar, J. The carnitine and of fatty acid metabolism in rat liver in thyroid PubMed Scopus Google Scholar, M.S. hormone carnitine expression in the and Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). In we have that the expression of and and and the key PGC1 is decreased in liver and the of (LPS) A.P. Moser A.H. Shigenaga J.K. Grunfeld C. Feingold K.R. The acute phase response is associated with retinoid X receptor repression in rodent liver.J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, A.P. Moser A.H. Shigenaga J.K. Grunfeld C. Feingold K.R. is associated with decreased expression and in J. Physiol. PubMed Scopus Google Scholar, K. Kim M.S. Shigenaga J. Moser Grunfeld C. Altered expression of nuclear hormone receptors and coactivators in the acute-phase J. Physiol. 2004; PubMed Scopus Google Scholar). In PPARα and genes that are in FA metabolism in these are also that the decrease in these nuclear hormone receptors and coactivators an role in lipid metabolism the acute-phase response (2Khovidhunkit W. Kim M.S. Memon R.A. Shigenaga J.K. Moser A.H. Feingold K.R. Grunfeld C. Effects of infection and inflammation on lipid and lipoprotein metabolism: mechanisms and consequences to the host.J. Lipid Res. 2004; 45: 1169-1196Abstract Full Text Full Text PDF PubMed Scopus (1102) Google Scholar, 9Beigneux A.P. Moser A.H. Shigenaga J.K. Grunfeld C. Feingold K.R. The acute phase response is associated with retinoid X receptor repression in rodent liver.J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, A.P. Moser A.H. Shigenaga J.K. Grunfeld C. Feingold K.R. is associated with decreased expression and in J. Physiol. PubMed Scopus Google Scholar, K. Kim M.S. Shigenaga J. Moser Grunfeld C. Altered expression of nuclear hormone receptors and coactivators in the acute-phase J. Physiol. 2004; PubMed Scopus Google Scholar). in adipose tissue, and expression is decreased the acute-phase response, which could contribute to the increase in lipolysis and circulating that the acute-phase response Moser A.H. Shigenaga J.K. Feingold K.R. Grunfeld C. nuclear hormone receptors, and repression in adipose tissue in the acute-phase Lipid Res. Full Text Full Text PDF PubMed Scopus Google Scholar). studies have that LPS results in a marked increase in TG in the kidney R.A. and Full Text Full Text PDF PubMed Scopus Google Scholar). In studies have that in the the mRNA levels of and required for TG were increased in LPS-treated which could contribute to the increase in TG levels in the kidney R.A. in renal alterations in and Full Text Full Text PDF PubMed Scopus Google Scholar). recent studies by have that the expression of and is decreased in the kidney LPS M.S. Shigenaga J. Moser Feingold K. Grunfeld C. of X receptor the acute phase Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, Y. Moser A.H. Shigenaga J.K. Grunfeld C. Feingold K.R. of liver X in kidney and by LPS and Lipid Res. Full Text Full Text PDF PubMed Scopus Google Scholar). that studies have suggested that the changes in FA and TG metabolism in the liver, heart, and adipose tissue the acute-phase response were in by changes in the expression of and we that LPS decrease the expression of and in leading to a decrease in FA which could contribute to the renal TG that with infection and LPS coli was and to the in was was and acid were was and were and and were the were in a with a and were with rodent and a were with of LPS in with The of LPS in effects on TG and metabolism, but is the for LPS in is body (3Feingold K.R. Staprans I. Memon R.A. Moser A.H. Shigenaga J.K. Doerrler W. Dinarello C.A. Grunfeld C. Endotoxin rapidly induces changes in lipid metabolism that produce hypertriglyceridemia: low doses stimulate hepatic triglyceride production while high doses inhibit clearance.J. Lipid Res. 1992; 33: 1765-1776Abstract Full Text PDF PubMed Google Scholar, G. C. Moser Dinarello C.A. Feingold K.R. Grunfeld C. to J. Physiol. 1999; Google Scholar). was the of LPS LPS induces in the were with an of and kidneys were and were to by the of the were with by kidney Lipid was by kidneys were and LPS-treated and in were with a tissue and were in and were with and in a for the was to the and was also to the the were to an which were the were and of were and to of kidney was of tissue was and by of was and on a The of was by of the to and and were as A.P. Moser A.H. Shigenaga J.K. Grunfeld C. Feingold K.R. The acute phase response is associated with retinoid X receptor repression in rodent liver.J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). were with mRNA levels were by by and was a P. 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PubMed Scopus Google Scholar, K. J. of the peroxisome proliferator-activated receptor in the effects of and fatty acids on Lipid Res. Full Text PDF PubMed Google Scholar). we the of LPS on the mRNA levels of the in in PPARα mRNA levels were decreased by in the kidney of LPS-treated In the mRNA levels of PPARβ/δ and were not in the kidney of LPS-treated to the of we were to PPARα protein levels in the kidney by available and and that LPS decreases the expression of PPARα in the we a decrease in which is an for PPARα in the kidney (2Khovidhunkit W. Kim M.S. Memon R.A. Shigenaga J.K. Moser A.H. Feingold K.R. Grunfeld C. Effects of infection and inflammation on lipid and lipoprotein metabolism: mechanisms and consequences to the host.J. Lipid Res. 2004; 45: 1169-1196Abstract Full Text Full Text PDF PubMed Scopus (1102) Google Scholar, Y. Moser A.H. Shigenaga J.K. Grunfeld C. Feingold K.R. of liver X in kidney and by LPS and Lipid Res. Full Text Full Text PDF PubMed Scopus Google Scholar). In addition to of also stimulates the expression of genes in FA metabolism, as and J. The metabolism of fatty acids in PubMed Scopus Google Scholar, J. The carnitine and of fatty acid metabolism in rat liver in thyroid PubMed Scopus Google Scholar, M.S. hormone carnitine expression in the and Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, M. and of hepatic metabolism of fatty acids in thyroid PubMed Scopus Google Scholar). the of LPS on mRNA levels of in the kidney LPS that and TRβ mRNA levels were by and results were seen decreased by and TRβ decreased by with the of mRNA levels of were also decreased by In we also the of LPS on the expression of other nuclear hormone receptors in the that the mRNA levels of receptor receptor and decrease with LPS In not with LPS studies by have that the acute-phase response not decreases the expression of key nuclear hormone receptors that lipid metabolism but also decreases coactivators that are required for the increase in that with of nuclear hormone receptors K. Kim M.S. Shigenaga J. Moser Grunfeld C. Altered expression of nuclear hormone receptors and coactivators in the acute-phase J. Physiol. 2004; PubMed Scopus Google Scholar, Moser A.H. Shigenaga J.K. Feingold K.R. Grunfeld C. nuclear hormone receptors, and repression in adipose tissue in the acute-phase Lipid Res. Full Text Full Text PDF PubMed Scopus Google Scholar, M.S. Shigenaga J.K. Moser Grunfeld C. Feingold K.R. factor and decrease and the coactivators and in liver Full Text Full Text PDF PubMed Scopus Google Scholar). the of LPS on mRNA levels in the and were decreased LPS and In mRNA levels of and were not by LPS results that the acute-phase response, in addition to the expression of specific nuclear hormone receptors, also decreases the expression of a of coactivators that is that PGC1 the expression of mitochondrial genes that play an role in C. proliferator-activated receptor energy and PubMed Scopus Google Scholar, of energy metabolism in and PubMed Scopus Google Scholar). we the of LPS on the expression of mitochondrial in the mRNA levels of COX5a, Idh3a, and decreased in the kidney of LPS-treated The studies were in mice. we changes in mice. In with there was a decrease in a decrease in a decrease in a decrease in a decrease in and a decrease in mRNA levels in the decreases in kidney expression are by LPS in and mice. in the mRNA levels of and were decreased in PPARα mice, with whereas the levels of and were In the mRNA levels of and were in PPARα and mice. LPS the mRNA levels of and LPS of the expression of these genes of Infection and inflammation to an increase in serum TG levels to an increase in VLDL production and a decrease in (2Khovidhunkit W. Kim M.S. Memon R.A. Shigenaga J.K. Moser A.H. Feingold K.R. Grunfeld C. Effects of infection and inflammation on lipid and lipoprotein metabolism: mechanisms and consequences to the host.J. Lipid Res. 2004; 45: 1169-1196Abstract Full Text Full Text PDF PubMed Scopus (1102) Google Scholar). The of LPS that produces is to that which produces and changes in acute-phase that the increase in serum TG levels is a response to infection a (2Khovidhunkit W. Kim M.S. Memon R.A. Shigenaga J.K. Moser A.H. Feingold K.R. Grunfeld C. Effects of infection and inflammation on lipid and lipoprotein metabolism: mechanisms and consequences to the host.J. Lipid Res. 2004; 45: 1169-1196Abstract Full Text Full Text PDF PubMed Scopus (1102) Google Scholar). In adipose tissue, lipolysis increases and the are to the liver, are into TG (2Khovidhunkit W. Kim M.S. Memon R.A. Shigenaga J.K. Moser A.H. Feingold K.R. Grunfeld C. Effects of infection and inflammation on lipid and lipoprotein metabolism: mechanisms and consequences to the host.J. Lipid Res. 2004; 45: 1169-1196Abstract Full Text Full Text PDF PubMed Scopus (1102) Google Scholar, 3Feingold K.R. Staprans I. Memon R.A. Moser A.H. Shigenaga J.K. Doerrler W. Dinarello C.A. Grunfeld C. Endotoxin rapidly induces changes in lipid metabolism that produce hypertriglyceridemia: low doses stimulate hepatic triglyceride production while high doses inhibit clearance.J. Lipid Res. 1992; 33: 1765-1776Abstract Full Text PDF PubMed Google Scholar). FA synthesis is and FA oxidation is the increased of FAs into TG (2Khovidhunkit W. Kim M.S. Memon R.A. Shigenaga J.K. Moser A.H. Feingold K.R. Grunfeld C. Effects of infection and inflammation on lipid and lipoprotein metabolism: mechanisms and consequences to the host.J. Lipid Res. 2004; 45: 1169-1196Abstract Full Text Full Text PDF PubMed Scopus (1102) Google Scholar, 3Feingold K.R. Staprans I. Memon R.A. Moser A.H. Shigenaga J.K. Doerrler W. Dinarello C.A. Grunfeld C. Endotoxin rapidly induces changes in lipid metabolism that produce hypertriglyceridemia: low doses stimulate hepatic triglyceride production while high doses inhibit clearance.J. Lipid Res. 1992; 33: 1765-1776Abstract Full Text PDF PubMed Google Scholar, M. Guiraud M. Grau G. Bouletreau P. Regulation of ketone body flux in septic patients.Am. J. Physiol. 1989; 257: E665-E674PubMed Google Scholar, 6Takeyama N. Itoh Y. Kitazawa Y. Tanaka T. Altered hepatic mitochondrial fatty acid oxidation and ketogenesis in endotoxic rats.Am. J. Physiol. 1990; 259: E498-E505Crossref PubMed Google Scholar). the production of TG is the to TG in fatty liver in the of fatty of the liver Full Text PDF PubMed Scopus Google Scholar). FA protein and are also decreased in heart, and adipose tissue LPS K. Kim M.S. Shigenaga J. Moser Grunfeld C. Altered expression of nuclear hormone receptors and coactivators in the acute-phase J. Physiol. 2004; PubMed Scopus Google Scholar, R.A. Feingold K.R. Moser A.H. J. Grunfeld C. Regulation of fatty acid transport protein and fatty acid mRNA levels by endotoxin and J. Physiol. Google Scholar, R.A. Moser A.H. J. Grunfeld C. Feingold K.R. of liver and specific fatty acid proteins by endotoxin and in 1999; PubMed Scopus Google Scholar). studies have a decrease in the and oxidation of FAs and an increase in the of TG in the with and LPS M.S. Spitzer J.J. In vitro effects of E. coli endotoxin on fatty acid and lactate oxidation in canine myocardium.Circ. Shock. 1977; 4: 181-190PubMed Google Scholar, 8Wang X. Evans R.D. Effect of endotoxin and platelet-activating factor on lipid oxidation in the rat heart.J. Mol. Cell. Cardiol. 1997; 29: 1915-1926Abstract Full Text PDF PubMed Scopus (17) Google Scholar). The by which infection and inflammation FA and TG metabolism is not understood, but recent studies have that LPS decreases the levels of and in liver, heart, and adipose tissue A.P. Moser A.H. Shigenaga J.K. Grunfeld C. Feingold K.R. The acute phase response is associated with retinoid X receptor repression in rodent liver.J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, A.P. Moser A.H. Shigenaga J.K. Grunfeld C. Feingold K.R. is associated with decreased expression and in J. Physiol. PubMed Scopus Google Scholar, K. Kim M.S. Shigenaga J. Moser Grunfeld C. Altered expression of nuclear hormone receptors and coactivators in the acute-phase J. Physiol. 2004; PubMed Scopus Google Scholar, Moser A.H. Shigenaga J.K. Feingold K.R. Grunfeld C. nuclear hormone receptors, and repression in adipose tissue in the acute-phase Lipid Res. Full Text Full Text PDF PubMed Scopus Google Scholar). including and that the of and also decrease in liver, heart, and adipose tissue LPS K. Kim M.S. Shigenaga J. Moser Grunfeld C. Altered expression of nuclear hormone receptors and coactivators in the acute-phase J. Physiol. 2004; PubMed Scopus Google Scholar, Moser A.H. Shigenaga J.K. Feingold K.R. Grunfeld C. nuclear hormone receptors, and repression in adipose tissue in the acute-phase Lipid Res. Full Text Full Text PDF PubMed Scopus Google Scholar, M.S. Shigenaga J.K. Moser Grunfeld C. Feingold K.R. factor and decrease and the coactivators and in liver Full Text Full Text PDF PubMed Scopus Google Scholar). In the liver and heart, a decrease in and PPARα and coactivators could contribute to the decreased FA whereas in adipose tissue, the decrease in and and coactivators could contribute to the increase in lipolysis A.P. Moser A.H. Shigenaga J.K. Grunfeld C. Feingold K.R. The acute phase response is associated with retinoid X receptor repression in rodent liver.J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, A.P. Moser A.H. Shigenaga J.K. Grunfeld C. Feingold K.R. is associated with decreased expression and in J. Physiol. PubMed Scopus Google Scholar, K. Kim M.S. Shigenaga J. Moser Grunfeld C. Altered expression of nuclear hormone receptors and coactivators in the acute-phase J. Physiol. 2004; PubMed Scopus Google Scholar, Moser A.H. Shigenaga J.K. Feingold K.R. Grunfeld C. nuclear hormone receptors, and repression in adipose tissue in the acute-phase Lipid Res. Full Text Full Text PDF PubMed Scopus Google Scholar, M.S. Shigenaga J.K. Moser Grunfeld C. Feingold K.R. factor and decrease and the coactivators and in liver Full Text Full Text PDF PubMed Scopus Google Scholar). by other have an increase in renal TG and cholesteryl ester levels in with LPS R.A. and Full Text Full Text PDF PubMed Scopus Google Scholar). In the we confirm these in the we that FA oxidation is decreased in the kidney of LPS-treated and is associated with a reduction in the expression of a of key proteins that are in FA by we a decrease in mRNA levels R.A. in renal alterations in and Full Text Full Text PDF PubMed Scopus Google Scholar). we also a decrease in the expression and and In the expression of the required for FA and FA synthase, is not in the kidney LPS that the decreased to FAs results in the increased of FAs, which increased for the synthesis of TG and cholesteryl is by the studies by other which have that LPS increases mRNA levels of and that TG synthesis FAs R.A. in renal alterations in and Full Text Full Text PDF PubMed Scopus Google Scholar). The expression of of the genes in FA oxidation and metabolism is regulated by PPARα and have that the levels of and the for PPARs and are in the kidney LPS M.S. Shigenaga J. Moser Feingold K. Grunfeld C. of X receptor the acute phase Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, Y. Moser A.H. Shigenaga J.K. Grunfeld C. Feingold K.R. of liver X in kidney and by LPS and Lipid Res. Full Text Full Text PDF PubMed Scopus Google Scholar). In the we that LPS and TRβ expression in In the expression of key and that the of PPARs to increase is also decreased in the kidneys of LPS-treated effects are the expression of other PPARs and and other coactivators and is not in the kidneys of LPS-treated The decrease in and mRNA levels could contribute to the decrease in mRNA levels of and and for the reduction in FA oxidation in the kidney infection and the changes in the of FA oxidation and the increase in TG in the kidney the changes observed in the liver and and are of a coordinated response infection and PPARα is an factor in the expression of genes in FA oxidation proliferator-activated genes to Res. PubMed Scopus Google Scholar, K. J. of the peroxisome proliferator-activated receptor in the effects of and fatty acids on Lipid Res. Full Text PDF PubMed Google Scholar), studies in PPARα that the expression of genes in FA mRNA levels in the kidney are by in PPARα mice, an role for PPARα in the expression of LPS in a reduction in mRNA is that expression is regulated by M.S. hormone carnitine expression in the and Biol. Full Text Full Text PDF PubMed Scopus Google Scholar), and LPS decreases in and PPARα mice. the decrease in the expression of a of LPS is to the decrease in key factor coactivators as and is to also the expression of on the potential effects of serum TG levels and FA oxidation in key as the and kidney infection and However, infection and there is an increase in serum which could lipid for other that play a role in host defense tissue (2Khovidhunkit W. Kim M.S. Memon R.A. Shigenaga J.K. Moser A.H. Feingold K.R. Grunfeld C. Effects of infection and inflammation on lipid and lipoprotein metabolism: mechanisms and consequences to the host.J. Lipid Res. 2004; 45: 1169-1196Abstract Full Text Full Text PDF PubMed Scopus (1102) Google Scholar). by have that LPS stimulates the of TG by Feingold K.R. Moser A.H. Grunfeld C. Lipopolysaccharide of induces lipid and Full Text PDF PubMed Scopus Google Scholar). studies have that as endotoxin and acid and effects (2Khovidhunkit W. Kim M.S. Memon R.A. Shigenaga J.K. Moser A.H. Feingold K.R. Grunfeld C. Effects of infection and inflammation on lipid and lipoprotein metabolism: mechanisms and consequences to the host.J. Lipid Res. 2004; 45: 1169-1196Abstract Full Text Full Text PDF PubMed Scopus (1102) Google Scholar). decrease in the and oxidation of FAs in and kidney could be of a coordinated systemic response to TG available for host defense and/or tissue repair. In addition to the potential is that the decrease in FA and oxidation in as the and kidney could have The oxidation of FA produces energy as with the oxidation of FA oxidation is an energy for these The kidney requires energy to support the transport of and in the severe including renal W. renal failure and Engl. J. Med. 2004; PubMed Scopus Google Scholar), and that the inability to generate energy via FA oxidation might contribute to the of In the that LPS increases kidney TG, and cholesteryl ester increases in be for by a decrease in FA oxidation to the decreased expression of key proteins required for the and oxidation of key that FA oxidation and metabolism, and and key and are in the kidney by LPS and might of the alterations in FA metabolism that infection and