In vivo regulation of acyl-CoA synthetase mRNA and activity by endotoxin and cytokines.

Acyl-CoA synthetase (ACS) catalyzes the activation of fatty acids (FA) to acyl-CoA esters, which are further metabolized in either anabolic or catabolic pathways. Endotoxin [lipopolysaccharide (LPS)], tumor necrosis factor (TNF), and interleukin-1 (IL-1) enhance hepatic FA synthesis and reesterification and inhibit FA oxidation. LPS also decreases triglyceride storage in adipose tissue and inhibits the uptake of FA by heart and muscle. Therefore, in this study we examined the effects of LPS and cytokines on ACS (now also known as ACS1) mRNA expression and activity in multiple tissues in Syrian hamsters. LPS markedly decreased ACS1 mRNA levels in liver, adipose tissue, heart, and skeletal muscle. The inhibitory effects of LPS on ACS1 mRNA levels in liver and adipose tissue were observed as early as 2-4 h after administration, became maximal by 4-8 h, and were sustained for >/=24 h. Very low doses of LPS (0.1-1 microg/100 g body wt) were needed to reduce ACS1 mRNA levels in liver and adipose tissue. TNF and IL-1 mimicked the effect of LPS on ACS1 mRNA levels in liver and adipose tissue. LPS decreased ACS activity in adipose tissue, heart, and muscle. In liver, where ACS is localized in several subcellular organelles, both LPS and cytokines decreased mitochondrial ACS activity, whereas they increased microsomal ACS activity. Taken together, these results indicate that LPS and cytokines decrease ACS1 mRNA expression and ACS activity in tissues where FA uptake and/or oxidation is decreased during sepsis. In liver, where FA oxidation is decreased during sepsis but the reesterification of FA is increased, LPS and cytokines decrease ACS1 mRNA and mitochondrial ACS activity, which may inhibit FA oxidation, but increase microsomal ACS activity, which may support the reesterification of peripherally derived FA for triglyceride synthesis.

[1]  P. Grimaldi,et al.  Cloning of a rat adipocyte membrane protein implicated in binding or transport of long-chain fatty acids that is induced during preadipocyte differentiation. Homology with human CD36. , 1993, The Journal of biological chemistry.

[2]  K. Feingold,et al.  Tumor necrosis factor mediates the effects of endotoxin on cholesterol and triglyceride metabolism in mice. , 1993, Endocrinology.

[3]  K. Feingold,et al.  Discordant regulation of proteins of cholesterol metabolism during the acute phase response. , 1995, Journal of lipid research.

[4]  T. Tanaka,et al.  Purification and properties of long-chain acyl-coenzyme-A synthetase from rat liver. , 1979, European journal of biochemistry.

[5]  A. Tabares,et al.  Triglyceride kinetics, tissue lipoprotein lipase, and liver lipogenesis in septic rats. , 1990, The American journal of physiology.

[6]  K. Feingold,et al.  Differential effects of interleukin-1 and tumor necrosis factor on ketogenesis. , 1992, The American journal of physiology.

[7]  J. Kondo,et al.  Structure and regulation of rat long-chain acyl-CoA synthetase. , 1990, The Journal of biological chemistry.

[8]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[9]  K. Feingold,et al.  Effects of TNF, IL-1, and the combination of both cytokines on cholesterol metabolism in Syrian hamsters. , 1994, Lymphokine and cytokine research.

[10]  P. Smith,et al.  Physiological concentrations of insulin and T3 stimulate 3T3-L1 adipocyte acyl-CoA synthetase gene transcription. , 1996, The American journal of physiology.

[11]  J. Spitzer,et al.  Free fatty acid utilization by skeletal muscle after endotoxin administration. , 1980, The American journal of physiology.

[12]  H. Lodish,et al.  Expression cloning and characterization of a novel adipocyte long chain fatty acid transport protein , 1994, Cell.

[13]  J. Spitzer,et al.  Myocardial substrate utilization in dogs following endotoxin administration. , 1974, The American journal of physiology.

[14]  J. McGarry,et al.  Regulation of ketogenesis and the renaissance of carnitine palmitoyltransferase. , 1989, Diabetes/metabolism reviews.

[15]  Tokuo T. Yamamoto,et al.  Molecular Characterization and Expression of Rat Acyl-CoA Synthetase 3* , 1996, The Journal of Biological Chemistry.

[16]  D. Potter,et al.  Induction of hepatic synthesis of serum amyloid A protein and actin. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[17]  N. Færgeman,et al.  Role of long-chain fatty acyl-CoA esters in the regulation of metabolism and in cell signalling. , 1997, The Biochemical journal.

[18]  K. Lippel.  Regulation of rat liver acyl-CoA synthetase activity. , 1971, Biochimica et biophysica acta.

[19]  K. Feingold,et al.  Effects of endotoxin and cytokines on lipid metabolism. , 1994, Current opinion in lipidology.

[20]  H. Lodish,et al.  Molecular mechanism of long-chain fatty acid uptake. , 1995, Trends in cardiovascular medicine.

[21]  J. Taylor,et al.  Effect of endotoxin on cholesterol biosynthesis and distribution in serum lipoproteins in Syrian hamsters. , 1993, Journal of lipid research.

[22]  H. Sasano,et al.  A novel arachidonate-preferring acyl-CoA synthetase is present in steroidogenic cells of the rat adrenal, ovary, and testis. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[23]  B. Corkey,et al.  CYTOKINES INHIBIT FATTY ACID OXIDATION IN ISOLATED RAT HEPATOCYTES: SYNERGY AMONG TNF, IL‐6, AND IL‐1 , 1994, Shock.

[24]  K. Feingold,et al.  Effect of interleukin-1 on lipid metabolism in the rat. Similarities to and differences from tumor necrosis factor. , 1991, Arteriosclerosis and thrombosis : a journal of vascular biology.

[25]  J. Spitzer,et al.  Contribution of different organs to increased glucose consumption after endotoxin administration. , 1987, The Journal of biological chemistry.

[26]  T. Funahashi,et al.  Marked reduction of acyl-CoA synthetase activity and mRNA in intra-abdominal visceral fat by physical exercise. , 1993, The American journal of physiology.

[27]  M. LaDu,et al.  Regulation of lipoprotein lipase in adipose and muscle tissues during fasting. , 1991, The American journal of physiology.

[28]  G. Bagby,et al.  Triacylglycerol kinetics in endotoxic rats with suppressed lipoprotein lipase activity. , 1987, The American journal of physiology.

[29]  Tokuo T. Yamamoto,et al.  Cloning and functional expression of a novel long-chain acyl-CoA synthetase expressed in brain. , 1992, Journal of biochemistry.

[30]  L. Daae,et al.  Fatty acid activation and acyl transfer in organs from rats in different nutritional states. , 1971, Biochimica et biophysica acta.

[31]  K. Feingold,et al.  Effect of endotoxin and cytokines on lipoprotein lipase activity in mice. , 1994, Arteriosclerosis and thrombosis : a journal of vascular biology.

[32]  K. Feingold,et al.  LPS and cytokines regulate extra hepatic mRNA levels of apolipoproteins during the acute phase response in Syrian hamsters. , 1997, Biochimica et biophysica acta.

[33]  N. Takeyama,et al.  Altered hepatic mitochondrial fatty acid oxidation and ketogenesis in endotoxic rats. , 1990, The American journal of physiology.

[34]  R. Bell,et al.  Triacylglycerol synthesis in isolated fat cells. An effect of insulin on microsomal fatty acid coenzyme A ligase activity. , 1976, The Journal of biological chemistry.

[35]  Kenneth R Feingold,et al.  Regulation of fatty acid transport protein and fatty acid translocase mRNA levels by endotoxin and cytokines. , 1998, American journal of physiology. Endocrinology and metabolism.

[36]  T. Hashimoto,et al.  Identity of long-chain acyl-coenzyme A synthetase of microsomes, mitochondria, and peroxisomes in rat liver. , 1985, Journal of biochemistry.

[37]  A. Tabares,et al.  Altered ketone body metabolism during gram-negative sepsis in the rat. , 1990, Metabolism: clinical and experimental.

[38]  J. Spitzer,et al.  Alterations in lipid and carbohydrate metabolism in sepsis. , 1988, JPEN. Journal of parenteral and enteral nutrition.

[39]  J. Friedman,et al.  Endotoxin and cytokines induce expression of leptin, the ob gene product, in hamsters. , 1996, The Journal of clinical investigation.

[40]  K. Feingold,et al.  Endotoxin rapidly induces changes in lipid metabolism that produce hypertriglyceridemia: low doses stimulate hepatic triglyceride production while high doses inhibit clearance. , 1992, Journal of lipid research.

[41]  J. Oram,et al.  Regulation of long chain fatty acid activation in heart muscle. , 1975, The Journal of biological chemistry.

[42]  C. Dinarello,et al.  Biologic basis for interleukin-1 in disease. , 1996, Blood.

[43]  F. Weiner,et al.  Regulation of gene expression by insulin and tumor necrosis factor alpha in 3T3-L1 cells. Modulation of the transcription of genes encoding acyl-CoA synthetase and stearoyl-CoA desaturase-1. , 1991, The Journal of biological chemistry.