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University of North Carolina, Chapel Hill, NC 27599-7461
3To whom correspondence should be addressed. E-mail: rcoleman{at}unc.edu.
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMolecular Characterization of...What is the Evidence...Why are the Different...Why Do ACS Message...ACS1: Nutritional and...Adipocyte ACS Activity is...Are Specific ACS Associated...Is Acyl-CoA Partitioning...Is There a Relationship...Perspective.LITERATURE CITED |
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(PPAR) and sterol regulatory element binding protein. Taken as a whole, these features suggest that in liver, ACS1 and ACS5 may provide acyl-CoA destined primarily for triacylglycerol synthesis or for mitochondrial oxidation, respectively. ACS4 may provide acyl-CoA for both synthesis and peroxisomal oxidation, depending on whether the enzyme is associated with the mitochondrial-associated membrane or with peroxisomes. It should be emphasized that although the data for acyl-CoA channeling are strong, they are indirect. Rigorous testing of these predictions will be required.
KEY WORDS: • diabetes • oxidation • triacylglycerol
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMolecular Characterization of...What is the Evidence...Why are the Different...Why Do ACS Message...ACS1: Nutritional and...Adipocyte ACS Activity is...Are Specific ACS Associated...Is Acyl-CoA Partitioning...Is There a Relationship...Perspective.LITERATURE CITED |
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Molecular Characterization of Rat ACS. |
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TOPABSTRACTINTRODUCTIONMolecular Characterization of...What is the Evidence...Why are the Different...Why Do ACS Message...ACS1: Nutritional and...Adipocyte ACS Activity is...Are Specific ACS Associated...Is Acyl-CoA Partitioning...Is There a Relationship...Perspective.LITERATURE CITED |
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). ACS1, ACS2 and ACS5 have 
60% amino acid identity with each other and 30% with the two members of the second subfamily, ACS3 and ACS4. Although all five ACS use saturated and unsaturated fatty acids of chain lengths 8–22 carbons, ACS4 has a marked preference for 20:4 and 20:5 (2
). Each of the ACS has a region that contains a putative AMP binding site and one that probably contains the fatty acid binding site (1
). These sites have been used to define the members of the ACS superfamily specific for different fatty acid chain lengths (3
). We will focus on the group that activates the most common fatty acids in the human diet, saturated and unsaturated fatty acids of 14–22 carbons. Despite a decade of active research on the cloned isoforms, a number of critical questions remain to be answered. |
What is the Evidence for Independent Functions of ACS Isoforms? |
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TOPABSTRACTINTRODUCTIONMolecular Characterization of...What is the Evidence...Why are the Different...Why Do ACS Message...ACS1: Nutritional and...Adipocyte ACS Activity is...Are Specific ACS Associated...Is Acyl-CoA Partitioning...Is There a Relationship...Perspective.LITERATURE CITED |
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). Additionally, acyl-CoA are cell-signaling molecules and may be ligands for transcription factors. As signals, acyl-CoA alter insulin secretion, apoptosis, and glucose transport and metabolism (4
). But why are multiple isoforms required to synthesize these acyl-CoA? Studies with triacsin C provided the initial evidence for ACS-catalyzed channeling of acyl-CoA in mammalian cells. When ACS is inhibited by triacsin, a fungal-derived competitive inhibitor, some pathways of lipid metabolism are completely blocked, whereas other pathways continue at near normal rates. For example, in human fibroblasts, triacsin C inhibits the incorporation of [3H]glycerol into phospholipid and triacylglycerol 80 and 99%, respectively, indicating severely impaired acylation of glycerol-3-phosphate, lysophosphatidic acid and diacylglycerol via the de novo synthetic pathway from glycerol-3-phosphate (Figs. 1
, 2
) (5
). Incorporation of [14C]oleate into triacylglycerol is also blocked 95%, consistent with impaired acylation via the de novo pathway. In contrast, incorporation of [14C]oleate into phospholipids is not impaired, suggesting that the reacylation pathway is functionally separate from de novo glycerolipid synthesis, and that separate pools of acyl-CoA exist. Troglitazone, a thiazolidinedione formerly used to treat type 2 diabetes, also selectively inhibits some, but not all acyl-CoA pathways (Fig. 3)
(6
). We hypothesized that triacsin and troglitazone must inhibit an ACS isoform that provides acyl-CoA for de novo lipid synthesis, and that a second ACS isoform, insensitive to the inhibitors, would provide acyl-CoA used to reacylate lysophospholipids.
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). These studies suggest that ACS1 and ACS4 provide acyl-CoA destined primarily for triacylglycerol synthesis and the de novo synthesis of phospholipids, but that phospholipid reacylation and oxidation must rely on acyl-CoA synthesized by other isoforms. |
Why are the Different ACS Isoforms Located on Different Cellular Membranes? |
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TOPABSTRACTINTRODUCTIONMolecular Characterization of...What is the Evidence...Why are the Different...Why Do ACS Message...ACS1: Nutritional and...Adipocyte ACS Activity is...Are Specific ACS Associated...Is Acyl-CoA Partitioning...Is There a Relationship...Perspective.LITERATURE CITED |
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73, 20 and 7%, respectively, of total cellular palmitoyl-CoA synthetase activity (8
). The ability to distinguish between the different isoforms allowed us and others to raise noncross-reacting peptide antibodies and show that in rat liver, ACS1 is an intrinsic membrane protein of the endoplasmic reticulum (ER) and of the mitochondrial-associated membrane (MAM), a locus that may be involved in the biogenesis of ER-mitochondrial membranes and/or VLDL secretion (1
). ACS1 is also present in adipocyte glucose transporter (GLUT) 4 vesicles and the plasma membrane. ACS4, the only isoform that is a peripheral membrane protein, is located in the MAM fraction and on the peroxisomal membrane. ACS5 is the only ACS identified to date that is located on the mitochondrial outer membrane (9
). These separate locations for ACS1, 4 and 5 are consistent with the idea that each ACS isoform catalyzes the synthesis of acyl-CoA that enter independent pathways (Fig. 2
). For example, the initial esterification steps in the synthesis of triacylglycerol and phospholipids occur in both ER and mitochondrial outer membrane, and although reesterification for remodeling of most phospholipids occurs in the ER, synthesis and remodeling of cardiolipin take place primarily in the mitochondria. Further, both mitochondria and peroxisomes are sites of fatty acyl-CoA oxidation.
It is difficult to conceptualize how the ACS are organized to have overlapping functions at different sites and separate functions at the same sites. The active site of each ACS faces the cytosol (1
), and acyl-CoA are fairly water-soluble, amphipathic molecules. Thus, they can theoretically partition into either membranes or cytosol. In liver cytosol, they may move freely or bind to acyl-CoA binding protein and to fatty acid binding protein. How then would an acyl-CoA be channeled into a specific pathway? One can envision physical interactions of the ACS with specific acyltransferases such as glycerolphosphate acyltransferase or CPT-1, but as yet, no evidence exists for such interactions.
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Why Do ACS Message Levels Vary in Different Tissues? |
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TOPABSTRACTINTRODUCTIONMolecular Characterization of...What is the Evidence...Why are the Different...Why Do ACS Message...ACS1: Nutritional and...Adipocyte ACS Activity is...Are Specific ACS Associated...Is Acyl-CoA Partitioning...Is There a Relationship...Perspective.LITERATURE CITED |
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). ACS2 and ACS3 were both cloned from a rat brain library and their mRNAs are expressed predominantly in brain and neural cell lines, although their developmental expression differs (10
,11
). ACS4, which prefers 20:4 and 20:5 fatty acids, is expressed at the highest levels in the adrenal gland (2
) where arachidonate comprises 40% of membrane fatty acids (12
) and 22% of fatty acids esterified to cholesterol (13
). Because arachidonate is part of a signaling cascade initiated by adrenocorticotropic hormone (ACTH) (14
), ACS4 might function to terminate the arachidonate signal, thereby diminishing cortisol synthesis. ACS5 mRNA expression is greatest in intestinal epithelial cells (1
), but its regulation has not been studied. ACS may also increase the vectorial transport of fatty acid into cells; whether exogenous fatty acids require a protein transporter or can cross the plasma membrane by diffusion, activation to acyl-CoA renders cell entry unidirectional. |
ACS1: Nutritional and Developmental Regulation Correlates with Triacylglycerol Synthesis. |
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TOPABSTRACTINTRODUCTIONMolecular Characterization of...What is the Evidence...Why are the Different...Why Do ACS Message...ACS1: Nutritional and...Adipocyte ACS Activity is...Are Specific ACS Associated...Is Acyl-CoA Partitioning...Is There a Relationship...Perspective.LITERATURE CITED |
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). ACS1 mRNA also increases in liver, heart and adipose tissue with refeeding after food deprivation, with obesity and diabetes in rodent models, and in adipose tissue after peroxisomal proliferator-activated receptor-
(PPAR) stimulation (1
,15
). ACS1 mRNA in liver and adipose tissue is higher in Zucker fa/fa rats than in their lean littermates (16
), in adipose tissue from rats with obesity caused by lesions in the ventromedial hypothalamus (17
) and in insulin-treated 3T3-L1 adipocytes (18
). In contrast, exercise decreases ACS1 activity and mRNA in rat visceral fat (19
). These studies are all compatible with the hypothesis that ACS1 synthesizes acyl-CoA that are used primarily for the synthesis of triacylglycerol. |
Adipocyte ACS Activity is Inhibited by a cAMP Pathway. |
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TOPABSTRACTINTRODUCTIONMolecular Characterization of...What is the Evidence...Why are the Different...Why Do ACS Message...ACS1: Nutritional and...Adipocyte ACS Activity is...Are Specific ACS Associated...Is Acyl-CoA Partitioning...Is There a Relationship...Perspective.LITERATURE CITED |
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). ACS1, the isoform expressed only in differentiated 3T3-L1 adipocytes, would be a good candidate for this type of regulation; however, the evidence is indirect because the studies that suggested regulation by phosphorylation were performed before the ACS isoforms were cloned. These studies should now be performed with the cloned ACS isoforms. |
Are Specific ACS Associated with Oxidation? |
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TOPABSTRACTINTRODUCTIONMolecular Characterization of...What is the Evidence...Why are the Different...Why Do ACS Message...ACS1: Nutritional and...Adipocyte ACS Activity is...Are Specific ACS Associated...Is Acyl-CoA Partitioning...Is There a Relationship...Perspective.LITERATURE CITED |
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(20
–22
), suggesting that ACS1 may also synthesize acyl-CoA that are destined for oxidation. Up-regulation is controlled by multiple promoters that result in three different mRNAs (A, B and C) differing in their 5'-untranslated regions (20
). The A type of ACS1 mRNA is normally expressed in heart, adipose, and liver. In PPAR-/- mice, the constitutive level of hepatic ACS1 protein decreases, showing that PPAR is required for both normal as well as activated expression of ACS1 (23
). The C type is expressed in heart and liver. Peroxisomal proliferators increase both A and C in liver, but the B type is observed in liver only after peroxisomal proliferators are given. Although no functional data or changes in relative subcellular localization were presented, Suzuki et al. (20
) hypothesized that the A type of ACS1 mRNA was linked to lipogenesis, and the B and C types to peroxisomal ß-oxidation. Because each of these different promoters results in the translation of the same open reading frame, it is difficult to understand how the ACS proteins produced would be associated with different functions unless the mRNA itself targeted newly synthesized ACS to specific membranes or allowed interaction with specific pathways. Although these authors attributed the increase in ACS1 with PPAR activation to a mitochondrial form related to ß-oxidation, our studies show that ACS1 protein is not present in mitochondria or peroxisomes (24
,25
). Thus, the function of ACS1 remains unknown.
ACS4 and ACS5 are located in peroxisomes and mitochondria, respectively; thus, they might provide activated fatty acids for oxidation. Unlike ACS1, the expression of ACS5 mRNA does not change during adipocyte differentiation of 3T3-L1 cells, suggesting a function unrelated to triacylglycerol synthesis (1
,9
,26
). However, ACS5 mRNA increases after food deprivation (9
) and parallels ß-oxidation. Further, in rats treated with a PPAR activator, ACS5 mRNA in brown adipose tissue increases about sixfold (15
). High ACS4 is observed in liver peroxisomes of rats treated with the PPAR activator gemfibrizol and might thereby provide some polyunsaturated fatty acyl-CoA for peroxisomal oxidation (25
). Consistent with a deficiency in arachidonoyl-CoA metabolism, female ACS4+/- mice have increased uterine prostaglandin E2 (PGE2), 6-keto PGF1, and PGF2 (27
). Taken as a whole, ACS4 and 5 seem less likely to be linked to triacylglycerol synthesis than ACS1, and their locations and responses to physiological stimuli suggest that they may activate fatty acids required for ß-oxidation.
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Is Acyl-CoA Partitioning Involved in Lipid-Mediated Toxicity in Type 2 Diabetes? |
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TOPABSTRACTINTRODUCTIONMolecular Characterization of...What is the Evidence...Why are the Different...Why Do ACS Message...ACS1: Nutritional and...Adipocyte ACS Activity is...Are Specific ACS Associated...Is Acyl-CoA Partitioning...Is There a Relationship...Perspective.LITERATURE CITED |
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). The resulting large increases in islet triacylglycerol content are accompanied by ß-cell apoptosis, which increases after islets are incubated with fatty acids and is preceded by an 82% rise in ceramide content (29
). The metabolism of fatty acids to acyl-CoA seems essential for apoptosis because both apoptosis and the rise in ceramide are blocked by the ACS-1 and -4 inhibitor, triacsin C (29
). In addition, triacsin C increases the low content of the antiapoptosis factor Bcl-2 in these ß-cells, indicating that changes in Bcl-2 are mediated by acyl-CoA or their metabolites. High circulating fatty acids also inhibit insulin-stimulated glucose transport into muscle (30
). In obese Zucker fa/fa rats, the heart becomes dilated and has reduced contractility; troglitazone therapy decreased the elevated myocardial triacylglycerol and ceramide levels and the increased DNA laddering (a measure of apoptosis), and prevented the decline in contractile function (31
). Thus, acyl-CoA in ß-cells, skeletal muscle and heart are heavily implicated in both the etiology and complications of obesity, insulin resistance and diabetes. The ACS isoforms present in ß-cells and other tissues are imperfectly characterized and their subcellular locations have not been determined. More information is required to assess the effect of acyl-CoA partitioning on apoptosis. |
Is There a Relationship Between Acyl CoA Partitioning and Insulin Resistance? |
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TOPABSTRACTINTRODUCTIONMolecular Characterization of...What is the Evidence...Why are the Different...Why Do ACS Message...ACS1: Nutritional and...Adipocyte ACS Activity is...Are Specific ACS Associated...Is Acyl-CoA Partitioning...Is There a Relationship...Perspective.LITERATURE CITED |
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), impaired insulin secretion from ß-cells (29
,32
) and impaired muscle glucose uptake. Transgenic mice that lack fat have severe insulin resistance, defects in IRS1 and IRS2 activation of PI3-kinase in muscle and liver, and a doubling of liver and muscle triacylglycerol content, suggesting that insulin resistance develops when fat partitioning is altered between adipocytes and other tissues (33
). A current model proposes that accumulation of lipid metabolites leads to PKC activation and phosphorylation of insulin receptor substrates, which then fail to activate PI3-kinase, thereby impairing glucose transport; it was suggested that insulin resistance would be induced when fatty acyl-CoA or their metabolites accumulate in muscle and liver (34
). |
Perspective. |
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TOPABSTRACTINTRODUCTIONMolecular Characterization of...What is the Evidence...Why are the Different...Why Do ACS Message...ACS1: Nutritional and...Adipocyte ACS Activity is...Are Specific ACS Associated...Is Acyl-CoA Partitioning...Is There a Relationship...Perspective.LITERATURE CITED |
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activators (35
), which simultaneously up-regulate ACS1? Is ACS1 an essential component of the cellular fatty acid import machinery and, if so, why are additional ACS present on internal cell membranes? The answers to these questions should be forthcoming in the next few years and will likely lead to a search for therapeutic agents that target individual ACS associated with triacylglycerol synthesis or with ß-oxidation.
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FOOTNOTES |
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2 Manuscript received 29 January 2002. Revision accepted 9 May 2002.
4 Abbreviations used: ACS, acyl-CoA synthetase; ACTH, adrenocorticotropic hormone; CPT-1, carnitine palmitoyltransferase-1; ER, endoplasmic reticulum; GLUT, glucose transporter; MAM, mitochondrial-associated membrane; PG, prostaglandin; PKC, protein kinase C; PPAR, peroxisomal proliferator-activated receptor.
5 The acyl-CoA synthetase family that prefers long-chain fatty acids has been designated acyl-CoA synthetase (ACS) in rodents and fatty acid CoA ligase (FACL) in humans, but is also termed fatty acyl-CoA synthetase (FACS), and fatty acid CoA synthase.
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LITERATURE CITED |
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TOPABSTRACTINTRODUCTIONMolecular Characterization of...What is the Evidence...Why are the Different...Why Do ACS Message...ACS1: Nutritional and...Adipocyte ACS Activity is...Are Specific ACS Associated...Is Acyl-CoA Partitioning...Is There a Relationship...Perspective.LITERATURE CITED |
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1. Coleman, R. A., Lewin, T. M. & Muoio, D. M. (2000) Physiological and nutritional regulation of enzymes of triacylglycerol synthesis. Annu. Rev. Nutr. 20:77-103.[Medline]
2. Kang, M.-J., Fujino, T., Sasano, H., Minekura, H., Yabuki, N., Nagura, H., Iijima, H. & Yamamoto, T. T. (1997) A novel arachidonate-preferring acyl-CoA synthetase is present in steroidogenic cells of the rat adrenal, ovary, and testis. Proc. Natl. Acad. Sci. USA 94:2880-2884.
3. Steinberg, S. J., Morgenthaler, J., Heinzer, A. K., Smith, K. D. & Watkins, P. A. (2000) Very long-chain acyl-CoA synthetases: Human "bubblegum" represents a new family of proteins capable of activating very long-chain fatty acids. J. Biol. Chem. 275:35162-35169.
4. Færgeman, N. J. & Knudsen, J. (1997) Role of long-chain fatty acyl-CoA esters in the regulation of metabolism and in cell signalling. Biochem. J. 323:1-12.
5. Igal, R. A., Wang, P. & Coleman, R. A. (1997) Triacsin C blocks de novo synthesis of glycerolipids and cholesterol esters but not recycling of fatty acid into phospholipid: evidence for functionally separate pools of acyl-CoA. Biochem. J. 324:529-534.
6. Fulgencio, J. P., Kohl, C., Girard, J. & Pegorier, J. P. (1996) Troglitazone inhibits fatty acid oxidation and esterification, and gluconeogenesis in isolated hepatocytes from starved rats. Diabetes 45:1556-1562.[Abstract]
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9. Lewin, T. M., Kim, J.-H., Granger, D. A., Vance, J. E. & Coleman, R. A. (2001) Acyl-CoA synthetase isoforms 1, 4, and 5 are present in different subcellular membranes in rat liver and can be inhibited independently. J. Biol. Chem. 276:24674-24679.
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18. Weiner, F. R., Smith, P. J., Wertheimer, S. & Rubin, C. S. (1991) Regulation of gene expression by insulin and tumor necrosis factor in 3T3–L1 cells: modulation of the transcription of genes encoding acyl-CoA synthetase and stearoyl-CoA desaturase. J. Biol. Chem. 266:23525-23528.
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20. Suzuki, H., Watanabe, M., Fujino, T. & Yamamoto, T. (1995) Multiple promoters in rat acyl-CoA synthetase gene mediate differential expression of multiple transcripts with 5'-end heterogeneity. J. Biol. Chem. 270:9676-9682.
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25. Lewin, T. M., Van Horn, C. G., Krisans, S. K. & Coleman, R. A. (2002) Rat liver acyl-CoA synthetase 4 is a peripheral-membrane protein located in two distinct subcellular organelles, peroxisomes and mitochondrial associated membrane. Arch. Biochem. Biophys. (in press).
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27. Cho, Y. Y., Kang, M. J., Sone, H., Suzuki, T., Abe, M., Igarashi, M., Tokunaga, T., Ogawa, S., Takei, Y. A., Miyazawa, T., Sasano, H., Fujino, T. & Yamamoto, T. T. (2001) Abnormal uterus with polycysts, accumulation of uterine prostaglandins, and reduced fertility in mice heterozygous for acyl-CoA synthetase 4 deficiency. Biochem. Biophys. Res. Commun. 284:993-997.[Medline]
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29. Shimabukuro, M., Zhou, Y.-T., Levi, M. & Unger, R. H. (1998) Fatty acid-induced ß cell apoptosis: a link between obesity and diabetes. Proc. Natl. Acad. Sci. USA 95:2498-2502.
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33. Kim, J., Gavrilova, O., Chen, Y., Reitman, M. & Schulman, G. I. (2000) Mechanisms of insulin resistance in A-ZIP/F-1 fatless mice. J. Biol. Chem. 275:8456-8460.
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H. Yao and J. Ye Long Chain Acyl-CoA Synthetase 3-mediated Phosphatidylcholine Synthesis Is Required for Assembly of Very Low Density Lipoproteins in Human Hepatoma Huh7 Cells J. Biol. Chem., January 11, 2008; 283(2): 849 - 854. [Abstract] [Full Text] [PDF]
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 J. Westerbacka, M. Kolak, T. Kiviluoto, P. Arkkila, J. Siren, A. Hamsten, R. M. Fisher, and H. Yki-Jarvinen Genes Involved in Fatty Acid Partitioning and Binding, Lipolysis, Monocyte/Macrophage Recruitment, and Inflammation Are Overexpressed in the Human Fatty Liver of Insulin-Resistant Subjects Diabetes, November 1, 2007; 56(11): 2759 - 2765. [Abstract] [Full Text] [PDF]
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 Y. Zhou, P. Abidi, A. Kim, W. Chen, T.-T. Huang, F. B. Kraemer, and J. Liu Transcriptional Activation of Hepatic ACSL3 and ACSL5 by Oncostatin M Reduces Hypertriglyceridemia Through Enhanced {beta}-Oxidation Arterioscler Thromb Vasc Biol, October 1, 2007; 27(10): 2198 - 2205. [Abstract] [Full Text] [PDF]
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K. Sjogren, K.-C. Leung, W. Kaplan, M. Gardiner-Garden, J. Gibney, and K. K. Y. Ho Growth hormone regulation of metabolic gene expression in muscle: a microarray study in hypopituitary men Am J Physiol Endocrinol Metab, July 1, 2007; 293(1): E364 - E371. [Abstract] [Full Text] [PDF]
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B. Askari, J. E. Kanter, A. M. Sherrid, D. L. Golej, A. T. Bender, J. Liu, W. A. Hsueh, J. A. Beavo, R. A. Coleman, and K. E. Bornfeldt Rosiglitazone Inhibits Acyl-CoA Synthetase Activity and Fatty Acid Partitioning to Diacylglycerol and Triacylglycerol via a Peroxisome Proliferator-Activated Receptor-{gamma}-Independent Mechanism in Human Arterial Smooth Muscle Cells and Macrophages Diabetes, April 1, 2007; 56(4): 1143 - 1152. [Abstract] [Full Text] [PDF]
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L. O. Li, D. G. Mashek, J. An, S. D. Doughman, C. B. Newgard, and R. A. Coleman Overexpression of Rat Long Chain Acyl-CoA Synthetase 1 Alters Fatty Acid Metabolism in Rat Primary Hepatocytes J. Biol. Chem., December 1, 2006; 281(48): 37246 - 37255. [Abstract] [Full Text] [PDF]
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 K. Milger, T. Herrmann, C. Becker, D. Gotthardt, J. Zickwolf, R. Ehehalt, P. A. Watkins, W. Stremmel, and J. Fullekrug Cellular uptake of fatty acids driven by the ER-localized acyl-CoA synthetase FATP4 J. Cell Sci., November 15, 2006; 119(22): 4678 - 4688. [Abstract] [Full Text] [PDF]
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 D. J. Durgan, J. K. Smith, M. A. Hotze, O. Egbejimi, K. D. Cuthbert, V. G. Zaha, J. R. B. Dyck, E. D. Abel, and M. E. Young Distinct transcriptional regulation of long-chain acyl-CoA synthetase isoforms and cytosolic thioesterase 1 in the rodent heart by fatty acids and insulin Am J Physiol Heart Circ Physiol, June 1, 2006; 290(6): H2480 - H2497. [Abstract] [Full Text] [PDF]
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N. D. Oakes, P. Thalen, E. Aasum, A. Edgley, T. Larsen, S. M. Furler, B. Ljung, and D. Severson Cardiac metabolism in mice: tracer method developments and in vivo application revealing profound metabolic inflexibility in diabetes Am J Physiol Endocrinol Metab, May 1, 2006; 290(5): E870 - E881. [Abstract] [Full Text] [PDF]
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J. S. Huo, R. C. McEachin, T. X. Cui, N. K. Duggal, T. Hai, D. J. States, and J. Schwartz Profiles of Growth Hormone (GH)-regulated Genes Reveal Time-dependent Responses and Identify a Mechanism for Regulation of Activating Transcription Factor 3 By GH J. Biol. Chem., February 17, 2006; 281(7): 4132 - 4141. [Abstract] [Full Text] [PDF]
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D. B. Jump, D. Botolin, Y. Wang, J. Xu, B. Christian, and O. Demeure Fatty Acid Regulation of Hepatic Gene Transcription J. Nutr., November 1, 2005; 135(11): 2503 - 2506. [Abstract] [Full Text] [PDF]
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A.-E. O. Jordal, B. E. Torstensen, S. Tsoi, D. R. Tocher, S. P. Lall, and S. E. Douglas Dietary Rapeseed Oil Affects the Expression of Genes Involved in Hepatic Lipid Metabolism in Atlantic Salmon (Salmo salar L.) J. Nutr., October 1, 2005; 135(10): 2355 - 2361. [Abstract] [Full Text] [PDF]
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 M. R. Van Gilst, H. Hadjivassiliou, and K. R. Yamamoto From The Cover: A Caenorhabditis elegans nutrient response system partially dependent on nuclear receptor NHR-49 PNAS, September 20, 2005; 102(38): 13496 - 13501. [Abstract] [Full Text] [PDF]
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 T. Mashima, T. Oh-hara, S. Sato, M. Mochizuki, Y. Sugimoto, K. Yamazaki, J.-i. Hamada, M. Tada, T. Moriuchi, Y. Ishikawa, et al. p53-Defective Tumors With a Functional Apoptosome-Mediated Pathway: A New Therapeutic Target J Natl Cancer Inst, May 18, 2005; 97(10): 765 - 777. [Abstract] [Full Text] [PDF]
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T. M. Lewin, S. Wang, C. A. Nagle, C. G. Van Horn, and R. A. Coleman Mitochondrial glycerol-3-phosphate acyltransferase-1 directs the metabolic fate of exogenous fatty acids in hepatocytes Am J Physiol Endocrinol Metab, May 1, 2005; 288(5): E835 - E844. [Abstract] [Full Text] [PDF]
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V. Foulon, M. Sniekers, E. Huysmans, S. Asselberghs, V. Mahieu, G. P. Mannaerts, P. P. Van Veldhoven, and M. Casteels Breakdown of 2-Hydroxylated Straight Chain Fatty Acids via Peroxisomal 2-Hydroxyphytanoyl-CoA Lyase: A REVISED PATHWAY FOR THE {alpha}-OXIDATION OF STRAIGHT CHAIN FATTY ACIDS J. Biol. Chem., March 18, 2005; 280(11): 9802 - 9812. [Abstract] [Full Text] [PDF]
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J. R. Marszalek, C. Kitidis, C. C. DiRusso, and H. F. Lodish Long-chain Acyl-CoA Synthetase 6 Preferentially Promotes DHA Metabolism J. Biol. Chem., March 18, 2005; 280(11): 10817 - 10826. [Abstract] [Full Text] [PDF]
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M. Gaster, A. C. Rustan, and H. Beck-Nielsen Differential Utilization of Saturated Palmitate and Unsaturated Oleate: Evidence From Cultured Myotubes Diabetes, March 1, 2005; 54(3): 648 - 656. [Abstract] [Full Text] [PDF]
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J. M. Caviglia, I. N. T. de Gomez Dumm, R. A. Coleman, and R. A. Igal Phosphatidylcholine deficiency upregulates enzymes of triacylglycerol metabolism in CHO cells J. Lipid Res., August 1, 2004; 45(8): 1500 - 1509. [Abstract] [Full Text] [PDF]
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B. P. Atshaves, A. M. McIntosh, O. I. Lyuksyutova, W. Zipfel, W. W. Webb, and F. Schroeder Liver Fatty Acid-binding Protein Gene Ablation Inhibits Branched-chain Fatty Acid Metabolism in Cultured Primary Hepatocytes J. Biol. Chem., July 23, 2004; 279(30): 30954 - 30965. [Abstract] [Full Text] [PDF]
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J. R. Marszalek, C. Kitidis, A. Dararutana, and H. F. Lodish Acyl-CoA Synthetase 2 Overexpression Enhances Fatty Acid Internalization and Neurite Outgrowth J. Biol. Chem., June 4, 2004; 279(23): 23882 - 23891. [Abstract] [Full Text] [PDF]
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Y.-L. Zhang, A. Hernandez-Ono, C. Ko, K. Yasunaga, L.-S. Huang, and H. N. Ginsberg Regulation of Hepatic Apolipoprotein B-lipoprotein Assembly and Secretion by the Availability of Fatty Acids: I. DIFFERENTIAL RESPONSE TO THE DELIVERY OF FATTY ACIDS VIA ALBUMIN OR REMNANT-LIKE EMULSION PARTICLES J. Biol. Chem., April 30, 2004; 279(18): 19362 - 19374. [Abstract] [Full Text] [PDF]
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J. M. Caviglia, L. O. Li, S. Wang, C. C. DiRusso, R. A. Coleman, and T. M. Lewin Rat Long Chain Acyl-CoA Synthetase 5, but Not 1, 2, 3, or 4, Complements Escherichia coli fadD J. Biol. Chem., March 19, 2004; 279(12): 11163 - 11169. [Abstract] [Full Text] [PDF]
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