Showing papers on "Acyl-CoA published in 2005"
TL;DR: The human acyl-CoA:diacylglycerol acyltransferase (DGAT) 2 gene superfamily comprises seven members, four of which have been previously implicated in the synthesis of di- or triacyl glycerol as mentioned in this paper.
109 citations
TL;DR: A critical role is demonstrated for ACS4 and MTE‐I in the hormonal regulation of steroidogenesis as a new pathway of arachidonic acid release different from the classical phospholipase A2 cascade.
Abstract: Arachidonic acid and its lypoxygenated metabolites play a fundamental role in the hormonal regulation of steroidogenesis. Reduction in the expression of the mitochondrial acyl-CoA thioesterase (MTE-I) by antisense or small interfering RNA (siRNA) and of the arachidonic acid-preferring acyl-CoA synthetase (ACS4) by siRNA produced a marked reduction in steroid output of cAMP-stimulated Leydig cells. This effect was blunted by a permeable analog of cholesterol that bypasses the rate-limiting step in steroidogenesis, the transport of cholesterol from the outer to the inner mitochondrial membrane. The inhibition of steroidogenesis was overcome by addition of exogenous arachidonic acid, indicating that the enzymes are part of the mechanism responsible for arachidonic acid release involved in steroidogenesis. Knocking down the expression of MTE-I leads to a significant reduction in the expression of steroidogenic acute regulatory protein. This protein is induced by arachidonic acid and controls the rate-limiting step. Overexpression of MTE-I resulted in an increase in cAMP-induced steroidogenesis. In summary, our results demonstrate a critical role for ACS4 and MTE-I in the hormonal regulation of steroidogenesis as a new pathway of arachidonic acid release different from the classical phospholipase A2 cascade.
67 citations
TL;DR: It is concluded that adiponectin induces an activation of AMPK in beta cells, which inhibits their cataplerosis of glucose-carbon to lipids.
53 citations
TL;DR: The observations reveal a plausible mechanism behind the disparate effects of acyl CoA saturation on K(ATP) channel activation and suggest that dietary fat composition may determine the severity of impaired GSIS via differential activation of beta-cell K( ATP) channels.
Abstract: Metabolic regulation of pancreatic β-cell ATP-sensitive K + channel (K ATP channel) function plays a key role in the process of glucose-stimulated insulin secretion (GSIS). Modulation of K ATP channel activity by long-chain acyl CoAs represents an important endogenous regulatory mechanism. Elevated acyl CoA levels have been reported in obese and type 2 diabetic individuals and may contribute to reduced β-cell excitability and impaired GSIS. Recent studies suggest that the composition of dietary fat may influence the effects of high-fat feeding on impaired GSIS. Therefore, we examined the effects of side-chain length and the degree of saturation of various acyl CoAs on K ATP channel activity. Macroscopic currents from either wild-type or polymorphic (Kir6.2[E23K/I337V]) recombinant β-cell K ATP channels were measured in inside-out patches by exposing the inner surface of the membrane to acyl CoAs at physiological nanomolar concentrations. Acyl CoAs increased both wild-type and polymorphic K ATP channel activity with the following rank order of efficacy: C18:0, C18:1 trans ∼ C18:1 cis , C20:4 = C16:0, C16:1, and C18:2. A significant correlation exists between activation and acyl CoA hydrophobicity, suggesting that both side-chain length and degree of saturation are critical determinants of K ATP channel activation. Our observations reveal a plausible mechanism behind the disparate effects of acyl CoA saturation on K ATP channel activation and suggest that dietary fat composition may determine the severity of impaired GSIS via differential activation of β-cell K ATP channels.
45 citations
TL;DR: It is suggested that AA, EPA, and DHA increase LDLrprotein levels, and that ACAT plays a role in modulating the effects of AA on LDLr protein levels, which appeared to be independent of any change in SREBP-1 protein.
Abstract: The objective of this study was to investigate the effect of individual PUFAs on LDL receptor (LDLr) expression in human fibroblasts and HepG2 cells, and to evaluate whether acyl CoA:cholesterol acyltransferase (ACAT) and sterol regulatory element-binding protein 1 (SREBP-1) were involved in the regulation of LDLr expression by fatty acids. When fibroblasts and HepG2 cells were cultured with serum-free defined medium for 48 h, there was a 3- to 5-fold (P 0.05) increase in LDLr protein and mRNA levels. Incubation of fibroblasts and HepG2 cells in serum-free medium supplemented with 25-hydroxycholesterol (25OH-cholesterol, 5 mg/L) for 24 h decreased LDLr protein and mRNA levels by 50 -90% (P 0.05). Arachidonic acid (AA, 20:4(n-6)), EPA (20:5(n-3)), and DHA (22:6(n-3)) antagonized the depression of LDLr gene expression by 25OH-cholesterol and increased LDLr protein abundance 1- to 3-fold (P 0.05), but had no significant effects on LDLr mRNA levels. Oleic (18:1), linoleic (18:2), and -linolenic acids (18:3(n-3)) did not significantly affect LDLr expression. ACAT inhibitor (58 - 035, 1 mg/L) attenuated the regulatory effect of AA on LDLr protein abundance by 40% (P 0.05), but did not modify the regulatory effects of other unsaturated fatty acids in HepG2 cells. The present results suggest that AA, EPA, and DHA increase LDLr protein levels, and that ACAT plays a role in modulating the effects of AA on LDLr protein levels. Furthermore, the effects of the fatty acids appeared to be independent of any change in SREBP-1 protein. J. Nutr. 135: 2541-2545, 2005.
42 citations
TL;DR: The generation and analysis of the corresponding Synechocystis knockout mutants revealed that lysophosphatidic acid acyltransferase unlike the lysphospholipid acyl transferase is essential for the vital functions of the cells.
41 citations
TL;DR: The acyl-CoA/free-acid and receptor/enzyme duality of HNF-4α extends the paradigm of nuclear receptors by controlling transcriptional activity by its two interrelated acyl ligands and two binding sites interphased in tandem by the thioesterase activity.
31 citations
TL;DR: A mutation of Bacillus subtilis (bfmB) is analyzed that results in an acyl-CoA:acyl-carrier-protein transacylase with low affinity for branched acyl -CoA substrates; it maps in the acf-hisH region of the chromosome.
Abstract: We have analyzed a mutation of Bacillus subtilis (bfmB) that results in an acyl-CoA:acyl-carrier-protein transacylase with low affinity for branched acyl-CoA substrates; it maps in the acf-hisH region of the chromosome. The aceA mutation, present in the parent of the bfmB mutant, causes a deficiency in pyruvate dehydrogenase and maps in the pycA-pyrA region. Strains carrying the bfmB mutation synthesize branched-chain fatty acids at a rate sufficient for normal growth only if branched acyl-CoA precursors are present in the medium. They grow well if the medium is supplemented with 0.1 mM 2-methylbutyrate, isobutyrate or isovalerate, or with 1.0 mM isoleucine or Jaline; leucine does not support growth. Growth supported by valine and isoleucine is inhibited by butyrate and other straight short-chain fatty acids at concentrations (0.1 mM) which do not inhibit growth of the standard strain; the inhibition is prevented by short branched fatty acids which are converted to long-chain fatty acids appearing as major constituents in membrane lipids. Other results suggest that the acyl-CoA:acyl-carrier-protein transacylase activity of B. subtilis is controlled by separate enzymatic sites for the acyl-CoA precursors of branched and straight chain fatty acids. Whether these sites are contained in one or two enzymes is not known.
16 citations