Coordinate regulation of the biosynthesis of ATP-citrate lyase and malic enzyme during adipocyte differentiation. Studies on 3T3-L1 cells.

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.

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

British Journal Of Nutrition ◽

10.1079/bjn2001392 ◽

2001 ◽

Vol 86 (3) ◽

pp. 371-377 ◽

Cited By ~ 52

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.

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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

British Journal Of Nutrition ◽

10.1079/bjn19730105 ◽

1973 ◽

Vol 29 (2) ◽

pp. 307-316 ◽

Cited By ~ 8

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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Factors involved in changes in hepatic lipogenesis during development of the rat

Biochemical Journal ◽

10.1042/bj1180155 ◽

1970 ◽

Vol 118 (1) ◽

pp. 155-162 ◽

Cited By ~ 49

Author(s):

Elizabeth A. Lockwood ◽

E. Bailey ◽

C. B. Taylor

Keyword(s):

Enzyme Activities ◽

Malic Enzyme ◽

Hormonal Control ◽

Male Rats ◽

Acetyl Coa Carboxylase ◽

Hepatic Enzymes ◽

Atp Citrate Lyase ◽

Acetyl Coa ◽

Citrate Lyase ◽

Glucose 6 Phosphate Dehydrogenase

1. Changes in the activities of acetyl-CoA carboxylase (EC 6.4.1.2), phosphofructokinase (EC 2.7.1.11), aldolase (EC 4.1.2.13), extramitochondrial aconitate hydratase (EC 4.2.1.3) and NADP-dependent isocitrate dehydrogenase (EC 1.1.1.42) have been measured in the livers of developing rats from late foetal life to maturity. 2. The effect of altering the weaning time on some enzymes associated with lipogenesis has been studied. Weaning rats at 15 days of age instead of 21 days results in an immediate increase in the activity of `malic' enzyme (EC 1.1.1.40) whereas the activities of glucose 6-phosphate dehydrogenase (EC 1.1.1.49) and ATP citrate lyase (EC 4.1.3.8) did not increase until 4–5 days and acetyl-CoA carboxylase 2–3 days after early weaning. Weaning rats on to an artificial-milk diet led to complete repression of the rise in activity of hepatic enzymes associated with lipogenesis normally found on weaning, except for `malic' enzyme, which increased in activity after 20 days of age. 3. The effect of intraperitoneal injections of glucagon, cortisol, growth hormone and thyroxine on the same hepatic enzymes has been investigated. Only thyroxine had any effect on enzyme activities and caused a 20-fold increase in `malic' enzyme activity and a twofold increase in ATP citrate lyase activity. 4. The activities of hepatic glucose 6-phosphate dehydrogenase and `malic' enzyme are higher in adult female than in adult male rats and it has been shown that this sex difference in enzyme activities is due to both male and female sex hormones. 5. Hepatic malate, citrate, pyruvate, glucose 6-phosphate and phosphoenolpyruvate concentrations have been measured throughout development. 6. The results are discussed in relation to the dietary and hormonal control of hepatic enzyme activities during development.

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Changes in hepatic lipogenesis during development of the rat

Biochemical Journal ◽

10.1042/bj1050717 ◽

1967 ◽

Vol 105 (2) ◽

pp. 717-722 ◽

Cited By ~ 88

Author(s):

C B Taylor ◽

E. Bailey ◽

W Bartley

Keyword(s):

Enzyme Activity ◽

Pyruvate Kinase ◽

Malic Enzyme ◽

Female Rats ◽

Male Rats ◽

Acetate Incorporation ◽

Atp Citrate Lyase ◽

Citrate Lyase ◽

Malic Enzyme Activity ◽

Glucose 6 Phosphate Dehydrogenase

1. Changes in the activities of ATP citrate lyase, ‘malic’ enzyme, glucose 6-phosphate dehydrogenase, pyruvate kinase and fructose 1,6-diphosphatase, and in the ability to incorporate [1−14C]acetate into lipid have been measured in the livers of developing rats between late foetal life and maturity. 2. In male rats the activities of those systems directly or indirectly concerned in lipogenesis (acetate incorporation into lipid, ATP citrate lyase and glucose 6-phosphate dehydrogenase) fall after birth and are maintained at a low value until weaning. After weaning these activities rise to a maximum between 30 and 40 days and then decline, reaching adult values at about 60 days. ‘Malic’ enzyme activity follows a similar course, except that none could be detected in the foetal liver. Pyruvate kinase activity is lower in foetal than in adult livers and rises to slightly higher than the adult value in the post-weaning period. Fructose 1,6-diphosphatase activity rises from a very low foetal value to reach a maximum at about 10 days but falls rapidly after weaning to reach adult values at about 30 days. 3. Weaning rats on to a high-fat diet caused the low activities of acetate incorporation, ATP citrate lyase, glucose 6-phosphate dehydrogenase and pyruvate kinase, characteristic of the suckling period, to persist. ‘Malic’ enzyme and fructose 1,6-diphosphatase activities were not altered appreciably. 4. No differences could be detected in hepatic enzyme activities between males and females up to 35 days, but after this time female rats gave higher values for acetate incorporation, glucose 6-phosphate dehydrogenase activity and ‘malic’ enzyme activity. 5. The results are discussed in relation to changes in alimentation and hormonal influences.

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

Annals of Microbiology ◽

10.1007/s13213-010-0159-4 ◽

2010 ◽

Vol 61 (3) ◽

pp. 463-468 ◽

Cited By ~ 18

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

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A Role for ATP-Citrate Lyase, Malic Enzyme, and Pyruvate/Citrate Cycling in Glucose-induced Insulin Secretion

Journal of Biological Chemistry ◽

10.1074/jbc.m707294200 ◽

2007 ◽

Vol 282 (49) ◽

pp. 35657-35665 ◽

Cited By ~ 107

Author(s):

Claudiane Guay ◽

S. R. Murthy Madiraju ◽

Alexandre Aumais ◽

Érik Joly ◽

Marc Prentki

Keyword(s):

Insulin Secretion ◽

Malic Enzyme ◽

Acid Oxidation ◽

Atp Citrate Lyase ◽

Protein Levels ◽

Metabolic Coupling ◽

Rnai Technology ◽

Citrate Lyase ◽

Malonyl Coa ◽

Coupling Factors

In pancreatic β-cells, metabolic coupling factors generated during glucose metabolism and pyruvate cycling through anaplerosis/cataplerosis processes contribute to the regulation of insulin secretion. Pyruvate/citrate cycling across the mitochondrial membrane leads to the production of malonyl-CoA and NADPH, two candidate coupling factors. To examine the implication of pyruvate/citrate cycling in glucose-induced insulin secretion (GIIS), different steps of the cycle were inhibited in INS 832/13 cells by pharmacological inhibitors and/or RNA interference (RNAi) technology: mitochondrial citrate export, ATP-citrate lyase (ACL), and cytosolic malic enzyme (ME1). The inhibitors of the di- and tri-carboxylate carriers, n-butylmalonate and 1,2,3-benzenetricarboxylate, respectively, reduced GIIS, indicating the importance of transmitochondrial transport of tri- and dicarboxylates in the action of glucose. To directly test the role of ACL and ME1 in GIIS, small hairpin RNA (shRNA) were used to selectively decrease ACL or ME1 expression in transfected INS 832/13 cells. shRNA-ACL reduced ACL protein levels by 67%, and this was accompanied by a reduction in GIIS. The amplification/KATP-independent pathway of GIIS was affected by RNAi knockdown of ACL. The ACL inhibitor radicicol also curtailed GIIS. shRNA-ME1 reduced ME1 activity by 62% and decreased GIIS. RNAi suppression of either ACL or ME1 did not affect glucose oxidation. However, because ACL is required for malonyl-CoA formation, inhibition of ACL expression by shRNA-ACL decreased glucose incorporation into palmitate and increased fatty acid oxidation in INS 832/13 cells. Taken together, the results underscore the importance of pyruvate/citrate cycling in pancreatic β-cell metabolic signaling and the regulation of GIIS.

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