scholarly journals Transcriptional regulation of phospholipid biosynthesis is linked to fatty acid metabolism by an acyl-CoA-binding-protein-dependent mechanism in Saccharomyces cerevisiae

2007 ◽  
Vol 407 (2) ◽  
pp. 219-230 ◽  
Author(s):  
Søren Feddersen ◽  
Thomas B. F. Neergaard ◽  
Jens Knudsen ◽  
Nils J. Færgeman
Keyword(s):  
Transcriptional Regulation ◽  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Binding Protein ◽  
Glycerol Metabolism ◽  
Pcr Analysis ◽  
Phospholipid Biosynthesis ◽  
Transcriptional Changes ◽  
High Concentrations

In the present study, we have used DNA microarray and quantitative real-time PCR analysis to examine the transcriptional changes that occur in response to cellular depletion of the yeast acyl-CoA-binding protein, Acb1p. Depletion of Acb1p resulted in the differential expression of genes encoding proteins involved in fatty acid and phospholipid synthesis (e.g. FAS1, FAS2, ACC1, OLE1, INO1 and OPI3), glycolysis and glycerol metabolism (e.g. GPD1 and TDH1), ion transport and uptake (e.g. ITR1 and HNM1) and stress response (e.g. HSP12, DDR2 and CTT1). In the present study, we show that transcription of the INO1 gene, which encodes inositol-3-phosphate synthase, cannot be fully repressed by inositol and choline, and UASINO1 (inositol-sensitive upstream activating sequence)-driven transcription is enhanced in Acb1p-depleted cells. In addition, the reduction in inositol-mediated repression of INO1 transcription observed after depletion of Acb1p appeared to be independent of the transcriptional repressor, Opi1p. We also demonstrated that INO1 and OPI3 expression can be normalized in Acb1p-depleted cells by the addition of high concentrations of exogenous fatty acids, or by the overexpression of FAS1 or ACC1. Together, these findings revealed an Acb1p-dependent connection between fatty acid metabolism and transcriptional regulation of phospholipid biosynthesis in yeast. Finally, expression of an Acb1p mutant which is unable to bind acyl-CoA esters could not normalize the transcriptional changes caused by Acb1p depletion. This strongly implied that gene expression is modulated either by the Acb1p–acyl-CoA ester complex directly or by its ability to donate acyl-CoA esters to utilizing systems.

scholarly journals Coordinated multitissue transcriptional and plasma metabonomic profiles following acute caloric restriction in mice

2006 ◽  
Vol 27 (3) ◽  
pp. 187-200 ◽  
Author(s):  
Colin Selman ◽  
Nicola D. Kerrison ◽  
Anisha Cooray ◽  
Matthew D. W. Piper ◽  
Steven J. Lingard ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Caloric Restriction ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Proton Nuclear Magnetic Resonance ◽  
Cellular Transport ◽  
Expression Of Genes ◽  
Transcriptional Changes

Caloric restriction (CR) increases healthy life span in a range of organisms. The underlying mechanisms are not understood but appear to include changes in gene expression, protein function, and metabolism. Recent studies demonstrate that acute CR alters mortality rates within days in flies. Multitissue transcriptional changes and concomitant metabolic responses to acute CR have not been described. We generated whole genome RNA transcript profiles in liver, skeletal muscle, colon, and hypothalamus and simultaneously measured plasma metabolites using proton nuclear magnetic resonance in mice subjected to acute CR. Liver and muscle showed increased gene expressions associated with fatty acid metabolism and a reduction in those involved in hepatic lipid biosynthesis. Glucogenic amino acids increased in plasma, and gene expression for hepatic gluconeogenesis was enhanced. Increased expression of genes for hormone-mediated signaling and decreased expression of genes involved in protein binding and development occurred in hypothalamus. Cell proliferation genes were decreased and cellular transport genes increased in colon. Acute CR captured many, but not all, hepatic transcriptional changes of long-term CR. Our findings demonstrate a clear transcriptional response across multiple tissues during acute CR, with congruent plasma metabolite changes. Liver and muscle switched gene expression away from energetically expensive biosynthetic processes toward energy conservation and utilization processes, including fatty acid metabolism and gluconeogenesis. Both muscle and colon switched gene expression away from cellular proliferation. Mice undergoing acute CR rapidly adopt many transcriptional and metabolic changes of long-term CR, suggesting that the beneficial effects of CR may require only a short-term reduction in caloric intake.

scholarly journals Valproic Acid Inhibits Leptin Secretion and Reduces Leptin Messenger Ribonucleic Acid Levels in Adipocytes

Endocrinology ◽  
2004 ◽  
Vol 145 (12) ◽  
pp. 5493-5503 ◽  
Author(s):  
Diane C. Lagace ◽  
Roger S. McLeod ◽  
Mark W. Nachtigal
Keyword(s):  
Valproic Acid ◽  
Fatty Acid ◽  
Weight Gain ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Binding Protein ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Messenger Ribonucleic Acid ◽  
Triacylglycerol Synthesis

Abstract Treatment of epilepsy or bipolar disorder with valproic acid (VPA) induces weight gain and increased serum levels for the satiety hormone, leptin, through an unidentified mechanism. In this study we tested the effects of VPA, a short-chain branched fatty acid (C8:0), on leptin biology and fatty acid metabolism in 3T3-L1 adipocytes. VPA significantly reduced leptin secretion in a dose-dependent manner. Because fatty acid accumulation has been hypothesized to block leptin secretion, we tested the effect of VPA on fatty acid metabolism. Using 14C-radiolabeled VPA, we found that the 14C was mainly incorporated into triacylglycerol. VPA did not alter lipogenesis from acetate, nor did it change the amount of intracellular free fatty acids available for triacylglycerol synthesis. Decreased leptin secretion was accompanied by a reduction in leptin mRNA, even though VPA treatment did not alter the protein levels for known transcription factors affecting leptin transcription including: CCAAT/enhancer binding protein-α, peroxisome proliferator-activated receptor-γ, or steroid regulatory element binding protein 1a. VPA altered levels of leptin mRNA independent of de novo protein synthesis without affecting leptin mRNA degradation. This report demonstrates that VPA decreases leptin secretion and mRNA levels in adipocytes in vitro, suggesting that VPA therapy may be associated with altered leptin homeostasis contributing to weight gain in vivo.

scholarly journals Anti-IL-17 Antibody Improves Hepatic Steatosis by Suppressing Interleukin-17-Related Fatty Acid Synthesis and Metabolism

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Weidong Shi ◽  
Qiang Zhu ◽  
Jian Gu ◽  
Xiaoshan Liu ◽  
Ling Lu ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Liver Disease ◽  
Hepatic Steatosis ◽  
Fatty Acid Metabolism ◽  
Alcoholic Liver Disease ◽  
Acid Metabolism ◽  
Binding Protein ◽  
Interleukin 17 ◽  
Expression Levels ◽  
Element Binding Protein

To investigate the relationship between interleukin-17 and proteins involved in fatty acid metabolism with respect to alcoholic liver disease, male ICR mice were randomized into five groups: control, alcoholic liver disease (ALD) at 4 weeks, 8 weeks, and 12 weeks, and anti-IL-17 antibody treated ALD. A proteomic approach was adopted to investigate changes in liver proteins between control and ALD groups. The proteomic analysis was performed by two-dimensional difference gel electrophoresis. Spots of interest were subsequently subjected to nanospray ionization tandem mass spectrometry (MS/MS) for protein identification. Additionally, expression levels of selected proteins were confirmed by western blot. Transcriptional levels of some selected proteins were determined by RT-PCR. Expression levels of 95 protein spots changed significantly (ratio >1.5,P<0.05) during the development of ALD. Sterol regulatory element-binding protein-lc (SREBP-1c), carbohydrate response element binding protein (ChREBP), enoyl-coenzyme A hydratase (ECHS1), and peroxisome proliferator-activated receptor alpha (PPAR-α) were identified by MS/MS among the proteins shown to vary the most; increased IL-17 elevated the transcription of SREBP-1c and ChREBP but suppressed ECHS1 and PPAR-α. The interleukin-17 signaling pathway is involved in ALD development; anti-IL-17 antibody improved hepatic steatosis by suppressing interleukin-17-related fatty acid metabolism.

scholarly journals Loss of the Acyl-CoA Binding Protein (Acbp) Results in Fatty Acid Metabolism Abnormalities in Mouse Hair and Skin

2007 ◽  
Vol 127 (1) ◽  
pp. 16-23 ◽  
Author(s):  
Lance Lee ◽  
C. Anthony DeBono ◽  
Dean R. Campagna ◽  
David C. Young ◽  
D. Branch Moody ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Binding Protein

scholarly journals Transfection of L6 myoblasts with adipocyte fatty acid-binding protein cDNA does not affect fatty acid uptake but disturbs lipid metabolism and fusion

1998 ◽  
Vol 329 (2) ◽  
pp. 265-273 ◽  
Author(s):  
F. M. Clemens PRINSEN ◽  
H. Jacques VEERKAMP
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Fatty Acid Binding Protein ◽  
Acid Metabolism ◽  
Binding Protein ◽  
Fatty Acid Uptake ◽  
Acid Uptake ◽  
Fatty Acid Binding ◽  
Transfected Cells ◽  
Acid Binding Protein

We studied the involvement of fatty acid-binding protein (FABP) in growth, differentiation and fatty acid metabolism of muscle cells by lipofection of rat L6 myoblasts with rat heart (H) FABP cDNA or with rat adipocyte (A) FABP cDNA in a eukaryotic expression vector which contained a puromycin acetyltransferase cassette. Stable transfectants showed integration into the genome for all constructs and type-specific overexpression at the mRNA and protein level for the clones with H-FABP and A-FABP cDNA constructs. The rate of proliferation of myoblasts transfected with rat A-FABP cDNA was 2-fold higher compared with all other transfected cells. In addition, these myoblasts showed disturbed fusion and differentiation, as assessed by morphological examination and creatine kinase activity. Uptake rates of palmitate were equal for all clone types, in spite of different FABP content and composition. Palmitate oxidation over a 3 h period was similar in all clones from growth medium. After being cultured in differentiation medium, mock- and H-FABP-cDNA-transfected cells showed a lower fatty acid-oxidation rate, in contrast with A-FABP-cDNA-transfected clones. The ratio of [14C]palmitic acid incorporation into phosphatidylcholine and phosphatidylethanolamine of A-FABP-cDNA-transfected clones changed in the opposite direction in differentiation medium from that of mock- and H-FABP-cDNA-transfected clones. In conclusion, transfection of L6 myoblasts with A-FABP cDNA does not affect H-FABP content and fatty acid uptake, but changes fatty acid metabolism. The latter changes may be related to the observed fusion defect.

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