The role of ATP citrate lyase, malic enzyme and fatty acid synthase in the regulation of lipid accumulation in Cunninghamella sp. 2A1

2010 ◽  
Vol 61 (3) ◽  
pp. 463-468 ◽  
Author(s):  
Aidil Abdul Hamid ◽  
Noor Fatmawati Mokhtar ◽  
Ekhlass M. Taha ◽  
Othman Omar ◽  
Wan Mohtar Wan Yusoff
Keyword(s):  
Fatty Acid ◽  
Lipid Accumulation ◽  
Malic Enzyme ◽  
Fatty Acid Synthase ◽  
Atp Citrate Lyase ◽  
Citrate Lyase

scholarly journals Strategic Feeding of Ammonium and Metal Ions for Enhanced GLA-Rich Lipid Accumulation inCunninghamella bainieri2A1

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Shuwahida Shuib ◽  
Wan Nazatul Naziah Wan Nawi ◽  
Ekhlass M. Taha ◽  
Othman Omar ◽  
Abdul Jalil Abdul Kader ◽  
...  
Keyword(s):  
Metal Ions ◽  
Lipid Content ◽  
Lipid Accumulation ◽  
Malic Enzyme ◽  
Fatty Acid Synthase ◽  
Ammonium Tartrate ◽  
Atp Citrate Lyase ◽  
Enzymes Activities ◽  
Citrate Lyase ◽  
Strategic Feeding

Strategic feeding of ammonium and metal ions (Mg2+, Mn2+, Fe3+, Cu2+, Ca2+, Co2+, and Zn2+) for enhanced GLA-rich lipid accumulation inC. bainieri2A1 was established. When cultivated in nitrogen-limited medium, the fungus produced up to 30% lipid (g/g biomass) with 12.9% (g/g lipid) GLA. However, the accumulation of lipid stopped at 48 hours of cultivation although glucose was abundant. This event occurred in parallel to the diminishing activity of malic enzyme (ME), fatty acid synthase (FAS), and ATP citrate lyase (ACL) as well as the depletion of metal ions in the medium. Reinstatement of the enzymes activities was achieved by feeding of ammonium tartrate, but no increment in the lipid content was observed. However, increment in lipid content from 32% to 50% (g/g biomass) with 13.2% GLA was achieved when simultaneous feeding of ammonium, glucose, and metal ions was carried out. This showed that the cessation of lipid accumulation was caused by diminishing activities of the enzymes as well as depletion of the metal ions in the medium. Therefore, strategic feeding of ammonium and metal ions successfully reinstated enzymes activities and enhanced GLA-rich lipid accumulation inC. bainieri2A1.

scholarly journals Glucose stimulates transcription of fatty acid synthase and malic enzyme in avian hepatocytes

1998 ◽  
Vol 274 (3) ◽  
pp. E493-E501 ◽  
Author(s):  
F. Bradley Hillgartner ◽  
Tina Charron
Keyword(s):  
Fatty Acid ◽  
High Fat Diet ◽  
Malic Enzyme ◽  
Fatty Acid Synthase ◽  
Primary Cultures ◽  
Pentose Phosphate ◽  
Mrna Abundance ◽  
Low Fat Diet ◽  
Low Carbohydrate

Transcription of fatty acid synthase (FAS) and malic enzyme (ME) in avian liver is low during starvation or feeding a low-carbohydrate, high-fat diet and high during feeding a high-carbohydrate, low-fat diet. The role of glucose in the nutritional control of FAS and ME was investigated by determining the effects of this metabolic fuel on expression of FAS and ME in primary cultures of chick embryo hepatocytes. In the presence of triiodothyronine, glucose (25 mM) stimulated an increase in the activity and mRNA abundance of FAS and ME. These effects required the phosphorylation of glucose to glucose 6-phosphate but not further metabolism downstream of the aldolase step of the glycolytic pathway. Xylitol mimicked the effects of glucose on FAS and ME expression, suggesting that an intermediate of the pentose phosphate pathway may be involved in mediating this response. The effects of glucose on the mRNA abundance of FAS and ME were accompanied by similar changes in transcription of FAS and ME. These data support the hypothesis that glucose plays a role in mediating the effects of nutritional manipulation on transcription of FAS and ME in liver.

scholarly journals RNA-seq reveals novel mechanistic targets of withaferin A in prostate cancer cells

2020 ◽  
Vol 41 (6) ◽  
pp. 778-789 ◽  
Author(s):  
Su-Hyeong Kim ◽  
Eun-Ryeong Hahm ◽  
Krishna B Singh ◽  
Sruti Shiva ◽  
Jacob Stewart-Ornstein ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Acid Synthesis ◽  
Acetyl Coa Carboxylase ◽  
Rna Seq ◽  
Atp Citrate Lyase ◽  
Acetyl Coa ◽  
Citrate Lyase

Abstract Withaferin A (WA) is a promising phytochemical exhibiting in vitro and in vivo anticancer activities against prostate and other cancers, but the mechanism of its action is not fully understood. In this study, we performed RNA-seq analysis using 22Rv1 human prostate cancer cell line to identify mechanistic targets of WA. Kyoto Encyclopedia of Genes and Genomes pathway analysis of the differentially expressed genes showed most significant enrichment of genes associated with metabolism. These results were validated using LNCaP and 22Rv1 human prostate cancer cells and Hi-Myc transgenic mice as models. The intracellular levels of acetyl-CoA, total free fatty acids and neutral lipids were decreased significantly following WA treatment in both cells, which was accompanied by downregulation of mRNA (confirmed by quantitative reverse transcription-polymerase chain reaction) and protein levels of key fatty acid synthesis enzymes, including ATP citrate lyase, acetyl-CoA carboxylase 1, fatty acid synthase and carnitine palmitoyltransferase 1A. Ectopic expression of c-Myc, but not constitutively active Akt, conferred a marked protection against WA-mediated suppression of acetyl-CoA carboxylase 1 and fatty acid synthase protein expression, and clonogenic cell survival. WA was a superior inhibitor of cell proliferation and fatty acid synthesis in comparison with known modulators of fatty acid metabolism including cerulenin and etomoxir. Intraperitoneal WA administration to Hi-Myc transgenic mice (0.1 mg/mouse, three times/week for 5 weeks) also resulted in a significant decrease in circulating levels of total free fatty acids and phospholipids, and expression of ATP citrate lyase, acetyl-CoA carboxylase 1, fatty acid synthase and carnitine palmitoyltransferase 1A proteins in the prostate in vivo.

scholarly journals Normal Flux through ATP-Citrate Lyase or Fatty Acid Synthase Is Not Required for Glucose-stimulated Insulin Secretion

2007 ◽  
Vol 282 (43) ◽  
pp. 31592-31600 ◽  
Author(s):  
Jamie W. Joseph ◽  
Matthew L. Odegaard ◽  
Sarah M. Ronnebaum ◽  
Shawn C. Burgess ◽  
Jeffrey Muehlbauer ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Atp Citrate Lyase ◽  
Citrate Lyase ◽  
Glucose Stimulated Insulin Secretion

Glucocorticoid regulation of fatty acid synthase gene expression in fetal rat lung

1993 ◽  
Vol 265 (2) ◽  
pp. L140-L147 ◽  
Author(s):  
Z. X. Xu ◽  
W. Stenzel ◽  
S. M. Sasic ◽  
D. A. Smart ◽  
S. A. Rooney
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Fatty Acid Biosynthesis ◽  
Fetal Lung ◽  
Acetyl Coa Carboxylase ◽  
Rat Lung ◽  
Acid Biosynthesis ◽  
Atp Citrate Lyase ◽  
Acetyl Coa ◽  
Citrate Lyase

There are developmental and glucocorticoid-induced increases in the rate of fatty acid biosynthesis and in the activity of fatty acid synthase in late gestation fetal lung. We have now measured mRNA levels of fatty acid synthase and of two other enzymes of fatty acid biosynthesis, ATP citrate lyase and acetyl-CoA carboxylase, in developing fetal and postnatal rat lung and in fetal lung explants cultured with and without dexamethasone. There was a developmental increase in the mRNA for fatty acid synthase with the maximum level being reached on fetal day 21 (term is fetal day 22). This profile was similar to that reported for de novo fatty acid synthesis and fatty acid synthase activity. There was a similar but less pronounced developmental increase in the mRNA for ATP citrate lyase and a corresponding increase in its activity. There was no developmental change in the mRNA for acetyl-CoA carboxylase. Dexamethasone increased the level of fatty acid synthase mRNA approximately threefold but had no effect on those for ATP citrate lyase and acetyl-CoA carboxylase. The effect of dexamethasone on fatty acid synthase mRNA was rapid, biphasic, and partly inhibited by actinomycin D and cycloheximide. We conclude that glucocorticoids increase expression of the gene for fatty acid synthase in fetal lung. The effect of the hormone appears to be due to increased transcription and post-transcriptional events and is dependent on protein synthesis.

scholarly journals Zonation of hepatic lipogenic enzymes identified by dual-digitonin-pulse perfusion

1989 ◽  
Vol 259 (3) ◽  
pp. 821-829 ◽  
Author(s):  
J L Evans ◽  
B Quistorff ◽  
L A Witters
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Fatty Acid Synthase ◽  
Acid Synthesis ◽  
Male Rats ◽  
Male Rat ◽  
Acetyl Coa Carboxylase ◽  
Atp Citrate Lyase ◽  
Acetyl Coa ◽  
Citrate Lyase

The zonal distribution within rat liver of acetyl-CoA carboxylase, ATP citrate-lyase and fatty acid synthase, the principal enzymes of fatty acid synthesis, was investigated by using dual-digitonin-pulse perfusion. Analysis of enzyme mass by immunoblotting revealed that, in normally feeding male rats, the periportal/perivenous ratio of acetyl-CoA carboxylase mass was 1.9. The periportal/perivenous ratio of ATP citrate-lyase mass was 1.4, and fatty acid synthase exhibited the largest periportal/perivenous mass gradient, having a ratio of 3.1. This pattern of enzyme distribution was observed in male rats only; in females, the periportal/perivenous ratio of enzyme mass was nearly equal. The periportal/perivenous gradients for acetyl-CoA carboxylase, ATP citrate-lyase and fatty acid synthase observed in fed (and fasted) males were abolished when animals were fasted (48 h) and refed (30 h) with a high-carbohydrate/low-fat diet. As determined by enzyme assay of eluates obtained from the livers of normally feeding male rats, there is also periportal zonation of acetyl-CoA carboxylase activity, expressed either as units per mg of eluted protein or units per mg of acetyl-CoA carboxylase protein, suggesting the existence of gradients in both enzyme mass and specific activity. From these results, we conclude that the enzymes of fatty acid synthesis are zonated periportally in the liver of the normally feeding male rat.

scholarly journals Polyunsaturated fatty acid-rich diets: effect on adipose tissue metabolism in rats

2001 ◽  
Vol 86 (3) ◽  
pp. 371-377 ◽  
Author(s):  
M. H. G. Gaíva ◽  
R. C. Couto ◽  
L. M. Oyama ◽  
G. E. C. Couto ◽  
V. L. F. Silveria ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Body Weight ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Malic Enzyme ◽  
Atp Citrate Lyase ◽  
Adipose Tissue Metabolism ◽  
Tissue Metabolism ◽  
Citrate Lyase

The aim of the present study was to evaluate the effect of diets rich in n-6 and n-3 fatty acids on adipose tissue metabolism. Starting at weaning, male Wistar rats were fed ad libitum, for 8 weeks with one of the following diets: C, rat chow; S, rat chow containing 15 % (w/w) soyabean oil; F, rat chow containing 15 % (w/w) fish oil; SF, rat chow containing 15 % (w/w) soyabean and fish oil (5:1, w/w). Casein was added to the fat diets to achieve the same 20 % (w/w) protein content as in the control chow. Food intake and body weight were measured weekly. The rats were killed by decapitation and the retroperitoneal (RET) and epididymal (EPI) white adipose tissues were removed and weighed. Tissue lipid and protein content, in vivo lipogenesis rate, uptake of diet-derived lipids, in vitro lipolytic rate, adipocyte area, lipoprotein lipase, ATP citrate lyase, and malic enzyme activities were evaluated. Carcass lipid and protein contents were also measured. Energy intake was reduced while carcass lipid content was increased in the three fat-fed groups. However, carcass protein and body weight gains were elevated only with diets F and SF. Lipolysis rate was diminished by diets F and SF, while the uptake of diet-derived lipids was elevated by the diet S in both RET and EPI tissues. These metabolic alterations may have contributed to the increase in in vivo lipogenesis rate in the presence of decreased ATP citrate lyase and malic enzyme activities induced by the three lipid diets. These results indicate that enrichment of the diet with polyunsaturated fatty acids causes changes in adipose tissue metabolism that favour fat deposition. Different metabolic pathways were preferentially affected by each type of fatty acid used.

scholarly journals Wnt10b Participates in Regulating Fatty Acid Synthesis in the Muscle of Zebrafish

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1011
Author(s):  
Dongwu Liu ◽  
Qiuxiang Pang ◽  
Qiang Han ◽  
Qilong Shi ◽  
Qin Zhang ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Glycogen Synthase ◽  
Fatty Acid Synthetase ◽  
Acid Synthesis ◽  
Atp Citrate Lyase ◽  
Enhancer Binding Protein ◽  
Citrate Lyase ◽  
Gsk 3Β

There are 19 Wnt genes in mammals that belong to 12 subfamilies. Wnt signaling pathways participate in regulating numerous homeostatic and developmental processes in animals. However, the function of Wnt10b in fatty acid synthesis remains unclear in fish species. In the present study, we uncovered the role of the Wnt10b signaling pathway in the regulation of fatty acid synthesis in the muscle of zebrafish. The gene of Wnt10b was overexpressed in the muscle of zebrafish using pEGFP-N1-Wnt10b vector injection, which significantly decreased the expression of glycogen synthase kinase 3β (GSK-3β), but increased the expression of β-catenin, peroxisome proliferators-activated receptor γ (PPARγ), and CCAAT/enhancer binding protein α (C/EBPα). Moreover, the activity and mRNA expression of key lipogenic enzymes ATP-citrate lyase (ACL), acetyl-CoA carboxylase (ACC) and fatty acid synthetase (FAS), and the content of non-esterified fatty acids (NEFA), total cholesterol (TC), and triglyceride (TG) were also significantly decreased. Furthermore, interference of the Wnt10b gene significantly inhibited the expression of β-catenin, PPARγ, and C/EBPα, but significantly induced the expression of GSK-3β, FAS, ACC, and ACL. The content of NEFA, TC, and TG as well as the activity of FAS, ACC, and ACL significantly increased. Thus, our results showed that Wnt10b participates in regulating fatty acid synthesis via β-catenin, C/EBPα and PPARγ in the muscle of zebrafish.

scholarly journals Sulforaphane downregulated fatty acid synthase and inhibited microtubule-mediated mitophagy leading to apoptosis

2021 ◽  
Vol 12 (10) ◽  
Author(s):  
Yuting Yan ◽  
Yan Zhou ◽  
Juntao Li ◽  
Zhongnan Zheng ◽  
Yabin Hu ◽  
...  
Keyword(s):  
Fatty Acid ◽  
High Performance ◽  
Fatty Acid Synthase ◽  
Atp Citrate Lyase ◽  
Transmission Electron ◽  
Citrate Lyase ◽  
Liquid Chromatography Tandem Mass ◽  
Associated Proteins ◽  
Mitochondrial Abnormality ◽  
Subcellular Level

AbstractWe previously demonstrated that sulforaphane (SFN) inhibited autophagy leading to apoptosis in human non-small cell lung cancer (NSCLC) cells, but the underlying subcellular mechanisms were unknown. Hereby, high-performance liquid chromatography-tandem mass spectrometry uncovered that SFN regulated the production of lipoproteins, and microtubule- and autophagy-associated proteins. Further, highly expressed fatty acid synthase (FASN) contributed to cancer malignancy and poor prognosis. Results showed that SFN depolymerized microtubules, downregulated FASN, and decreased its binding to α-tubulin; SFN downregulated FASN, acetyl CoA carboxylase (ACACA), and ATP citrate lyase (ACLY) via activating proteasomes and downregulating transcriptional factor SREBP1; SFN inhibited the interactions among α-tubulin and FASN, ACACA, and ACLY; SFN decreased the amount of intracellular fatty acid (FA) and mitochondrial phospholipids; and knockdown of FASN decreased mitochondrial membrane potential (ΔΨm) and increased reactive oxygen species, mitochondrial abnormality, and apoptosis. Further, SFN downregulated mitophagy-associated proteins Bnip3 and NIX, and upregulated mitochondrial LC3 II/I. Transmission electron microscopy showed mitochondrial abnormality and accumulation of mitophagosomes in response to SFN. Combined with mitophagy inducer CCCP or autophagosome–lysosome fusion inhibitor Bafilomycin A1, we found that SFN inhibited mitophagosome–lysosome fusion leading to mitophagosome accumulation. SFN reduced the interaction between NIX and LC3 II/I, and reversed CCCP-caused FA increase. Furthermore, knockdown of α-tubulin downregulated NIX and BNIP3 production, and upregulated LC3 II/I. Besides, SFN reduced the interaction and colocalization between α-tubulin and NIX. Thus, SFN might cause apoptosis via inhibiting microtubule-mediated mitophagy. These results might give us a new insight into the mechanisms of SFN-caused apoptosis in the subcellular level.

scholarly journals Changes in the activity of citrate lyase, malic enzyme and acetyl-CoA synthetase in rat liver after short-term and long-term feeding with ethanol

1973 ◽  
Vol 29 (2) ◽  
pp. 307-316 ◽  
Author(s):  
E. Fellenius ◽  
U. Nisbeth ◽  
L. Pilström ◽  
K.-H. Kiessling
Keyword(s):  
Malic Enzyme ◽  
Liquid Diet ◽  
Short Term ◽  
Atp Citrate Lyase ◽  
Acetyl Coa ◽  
Pronounced Increase ◽  
Ethanol Group ◽  
Citrate Lyase

1. The effect of short-term and long-term feeding (0–80 d) with a liquid diet containing ethanol on the activity of rat hepatic enzymes related to lipogenesis has been evaluated. Carbohydrates were isoenergetically substituted for ethanol in the control animals.2. The maximum concentration of triglycerides in the livers was reached after about 30 d, when it was almost three times as high as in the control animals. The activity of malic enzyme (EC 1·1·1·40) and ATP citrate lyase (EC 4·1·3·8) decreased significantly in the ethanol group, compared with the control rats, within 10 d and remained low during the rest of the experiment (80 d). After 20 d, the acetyl-CoA synthetase (EC 6·2·1·1) activity increased significantly in the livers of the ethanol-fed rats but fell subsequently to values similar to those in the livers of the control rats. Thus, despite a pronounced increase in the amount of triglyceride in the livers of rats on a liquid diet containing ethanol, there was a dramatic decrease in the activity of the enzymes (malic enzyme and citrate lyase) involved in lipogenesis.3. The almost unchanged activity of acetyl-CoA synthetase shows that the utilization of acetate, produced when ethanol is oxidized, is not stimulated by long-term feeding with ethanol. The involvement of citrate lyase in various postulated shuttles for the transport of reducing equivalents across the mitochondrial membrane and the role of malic enzyme in the microsomal ethanol-oxidizing system are discussed.

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