scholarly journals Effects of carbohydrate availability on lipogenesis in sheep

1972 ◽  
Vol 126 (1) ◽  
pp. 193-200 ◽  
Author(s):  
F. J. Ballard ◽  
O. H. Filsell ◽  
I. G. Jarrett
Keyword(s):  
Adipose Tissue ◽  
Pyruvate Carboxylase ◽  
Soluble Carbohydrate ◽  
Atp Citrate Lyase ◽  
Carbohydrate Availability ◽  
Triglyceride Fatty Acid ◽  
Citrate Lyase ◽  
Effect Of Glucose ◽  
Glucose Availability

1. Lipogenesis in sheep liver and adipose tissue was investigated by incorporation studies in vitro with radioactive glucose and acetate and by assays of key enzymes. 2. Carbohydrate availability to sheep was increased by feeding on a diet containing 70% soluble carbohydrate, by infusing glucose into the abomasum or by direct intravenous infusion of glucose. 3. Under these conditions lipogenesis from glucose and acetate was increased from very low values in lìver and adipose tissue, especially in those animals where rumen fermentation was by-passed by glucose infusion. 4. Large increases in the activities of ATP citrate lyase (EC 4.1.3.8) and NADP–malate dehydrogenase (EC 1.1.1.40) occurred in both tissues when lipogenesis was increased. 5. No adaptations were found in the activities of pyruvate carboxylase (EC 6.4.1.1) in adipose tissue, glucokinase (EC 2.7.1.2) in liver or 3-hydroxybutyrate dehydrogenase (EC 1.1.1.30) in liver. It is proposed that the absence of these enzymes is not related to glucose availability. 6. The effect of glucose on liver lipogenesis was to increase conversion of acetate into lipid. 7. This effect also occurred in adipose tissue, but in this tissue glucose also became a quantitatively important precursor of triglyceride fatty acid.

scholarly journals Effects of PKB/Akt inhibitors on insulin-stimulated lipogenesis and phosphorylation state of lipogenic enzymes in white adipose tissue

2020 ◽  
Vol 477 (8) ◽  
pp. 1373-1389
Author(s):  
Nusrat Hussain ◽  
Sheng-Ju Chuang ◽  
Manuel Johanns ◽  
Didier Vertommen ◽  
Gregory R. Steinberg ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Acute Effects ◽  
Lipogenic Enzymes ◽  
Atp Citrate Lyase ◽  
Phosphorylation State ◽  
Epididymal Fat ◽  
Citrate Lyase ◽  
Fat Pads

We investigated acute effects of two allosteric protein kinase B (PKB) inhibitors, MK-2206 and Akti-1/2, on insulin-stimulated lipogenesis in rat epididymal adipocytes incubated with fructose as carbohydrate substrate. In parallel, the phosphorylation state of lipogenic enzymes in adipocytes and incubated epididymal fat pads was monitored by immunoblotting. Preincubation of rat epididymal adipocytes with PKB inhibitors dose-dependently inhibited the following: insulin-stimulated lipogenesis, increased PKB Ser473 phosphorylation, increased PKB activity and decreased acetyl-CoA carboxylase (ACC) Ser79 phosphorylation. In contrast, the effect of insulin to decrease the phosphorylation of pyruvate dehydrogenase (PDH) at Ser293 and Ser300 was not abolished by PKB inhibition. Insulin treatment also induced ATP-citrate lyase (ACL) Ser454 phosphorylation, but this effect was less sensitive to PKB inhibitors than ACC dephosphorylation by insulin. In incubated rat epididymal fat pads, Akti-1/2 treatment reversed insulin-induced ACC dephosphorylation, while ACL phosphorylation by insulin was maintained. ACL and ACC purified from white adipose tissue were poor substrates for PKBα in vitro. However, effects of wortmannin and torin, along with Akti-1/2 and MK-2206, on recognized PKB target phosphorylation by insulin were similar to their effects on insulin-induced ACL phosphorylation, suggesting that PKB could be the physiological kinase for ACL phosphorylation by insulin. In incubated epididymal fat pads from wild-type versus ACC1/2 S79A/S212A knockin mice, effects of insulin to increase lipogenesis from radioactive fructose or from radioactive acetate were reduced but not abolished. Together, the results support a key role for PKB in mediating insulin-stimulated lipogenesis by decreasing ACC phosphorylation, but not by decreasing PDH phosphorylation.

scholarly journals Liposome-Mediated Inhibition of Inflammation by Hydroxycitrate

Nanomaterials ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 2080
Author(s):  
Antonio Vassallo ◽  
Valentina Santoro ◽  
Ilaria Pappalardo ◽  
Anna Santarsiero ◽  
Paolo Convertini ◽  
...  
Keyword(s):  
Biological Effect ◽  
Oxygen Species ◽  
Intracellular Accumulation ◽  
Atp Citrate Lyase ◽  
Garcinia Cambogia ◽  
Acid Component ◽  
Citrate Lyase ◽  
Consequent Reduction ◽  
Inflammatory Processes

Hydroxycitrate (HCA), a main organic acid component of the fruit rind of Garcinia cambogia, is a natural citrate analog that can inhibit the ATP citrate lyase (ACLY) enzyme with a consequent reduction of inflammatory mediators (i.e., nitric oxide (NO), reactive oxygen species (ROS), and prostaglandin E2 (PGE2)) levels. Therefore, HCA has been proposed as a novel means to prevent, treat, and ameliorate conditions involving inflammation. However, HCA presents a low membrane permeability, and a large quantity is required to have a biological effect. To overcome this problem, HCA was formulated in liposomes in this work, and the enhancement of HCA cell availability along with the reduction in the amount required to downregulate NO, ROS, and PGE2 in macrophages were assessed. The liposomes were small in size (~60 nm), monodispersed, negatively charged (−50 mV), and stable on storage. The in vitro results showed that the liposomal encapsulation increased by approximately 4 times the intracellular accumulation of HCA in macrophages, and reduced by 10 times the amount of HCA required to abolish LPS-induced NO, ROS, and PGE2 increase. This suggests that liposomal HCA can be exploited to target the citrate pathway involved in inflammatory processes.

Inhibition of lipogenesis by vasopressin and angiotensin II in glycogen-depleted hepatocytes

1983 ◽  
Vol 3 (11) ◽  
pp. 1063-1070 ◽  
Author(s):  
T. Norman Palmer ◽  
Margaret A. Caldecourt ◽  
David I. Watts ◽  
Mary C. Sugden
Keyword(s):  
Fatty Acid ◽  
Angiotensin Ii ◽  
Specific Inhibitor ◽  
Glycolytic Flux ◽  
Glycogen Depletion ◽  
Inhibitory Effects ◽  
Atp Citrate Lyase ◽  
Rate Determining Step ◽  
Citrate Lyase

Vasopressin and angiotensin II inhibited lipogenesis (measured with 3H2O) in hepatocytes from fed rats. Inhibition was also observed with hepatocytes from fed rats which had been depleted of glycogen in vitro and incubated with lactate + pyruvate (5 mM + 0.5 mM) as substrates. The inhibitory actions of the hormones are therefore independent of hormone-mediated changes in glycogenolytic or glycolytic flux from glycogen, and thus the site(s) of hormone action must be subsequent to the formation of lactate. (-)Hydroxycitrate, a specific inhibitor of ATP-citrate lyase, decreased lipogenesis in hepatocytes from fed rats incubated with lactate + pyruvate by approx. 51% but had little effect on lipogenesis in glycogen-depleted hepatocytes similarly incubated. There was parallel inhibition of incorporation of 14C from [U-14C]lactate into fatty acid and lipogenesis as measured with 3H2O in each case. Thus depletion of glycogen, or conceivably the process of glycogen-depletion (incubation with dibutyryl cyclic AMP) causes a change in the rate-determining step(s) for lipogenesis from lactate. Vasopressin and angiotensin II also decreased lipogenesis and incorporation of 14C into fatty acids in glycogen-depleted hepatocytes provided with [U-14C]proline as opposed to [U-14C]-lactate. However, proline-stimulated lipogenesis was inhibited by (-)hydroxycitrate, and proline-stimulated lipogenesis and incorporation of 14C from [U-14C]-proline were not decreased in parallel by this inhibitor (inhibition of 52% and 85% respectively). It is inferred that lactate and proline stimulate lipogenesis by different mechanisms and incorporation of 14C from [U-14C]proline and [U-14C]lactate into fatty acid occurs via different routes. (-)Hydroxycitrate diminished the inhibitory effects of the hormones in the presence of either lactate or proline, suggesting that flux through ATP-citrate lyase is important for the hormone response.

scholarly journals Intracellular localization of enzymes in white-adipose-tissue fat-cells and permeability properties of fat-cell mitochondria. Transfer of acetyl units and reducing power between mitochondria and cytoplasm

1970 ◽  
Vol 117 (5) ◽  
pp. 861-877 ◽  
Author(s):  
B. R. Martin ◽  
R. M. Denton
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Reducing Power ◽  
Acid Synthesis ◽  
Fat Cells ◽  
Carnitine Acetyltransferase ◽  
Fat Cell ◽  
Atp Citrate Lyase ◽  
Aconitate Hydratase ◽  
Citrate Lyase

1. A method is described for extracting separately mitochondrial and extramitochondrial enzymes from fat-cells prepared by collagenase digestion from rat epididymal fat-pads. The following distribution of enzymes has been observed (with the total activities of the enzymes as units/mg of fat-cell DNA at 25°C given in parenthesis). Exclusively mitochondrial enzymes: glutamate dehydrogenase (1.8), NAD–isocitrate dehydrogenase (0.5), citrate synthase (5.2), pyruvate carboxylase (3.0); exclusively extramitochondrial enzymes: glucose 6-phosphate dehydrogenase (5.8), 6-phosphogluconate dehydrogenase (5.2), NADP–malate dehydrogenase (11.0), ATP–citrate lyase (5.1); enzymes present in both mitochondrial and extramitochondrial compartments: NADP–isocitrate dehydrogenase (3.7), NAD–malate dehydrogenase (330), aconitate hydratase (1.1), carnitine acetyltransferase (0.4), acetyl-CoA synthetase (1.0), aspartate aminotransferase (1.7), alanine aminotransferase (6.1). The mean DNA content of eight preparations of fat-cells was 109μg/g dry weight of cells. 2. Mitochondria showing respiratory control ratios of 3–6 with pyruvate, about 3 with succinate and P/O ratios of approaching 3 and 2 respectively have been isolated from fat-cells. From studies of rates of oxygen uptake and of swelling in iso-osmotic solutions of ammonium salts, it is concluded that fat-cell mitochondria are permeable to the monocarboxylic acids, pyruvate and acetate; that in the presence of phosphate they are permeable to malate and succinate and to a lesser extent oxaloacetate but not fumarate; and that in the presence of both malate and phosphate they are permeable to citrate, isocitrate and 2-oxoglutarate. In addition, isolated fat-cell mitochondria have been found to oxidize acetyl l-carnitine and, slowly, l-glycerol 3-phosphate. 3. It is concluded that the major means of transport of acetyl units into the cytoplasm for fatty acid synthesis is as citrate. Extensive transport as glutamate, 2-oxoglutarate and isocitrate, as acetate and as acetyl l-carnitine appears to be ruled out by the low activities of mitochondrial aconitate hydratase, mitochondrial acetyl-CoA hydrolyase and carnitine acetyltransferase respectively. Pathways whereby oxaloacetate generated in the cytoplasm during fatty acid synthesis by ATP–citrate lyase may be returned to mitochondria for further citrate synthesis are discussed. 4. It is also concluded that fat-cells contain pathways that will allow the excess of reducing power formed in the cytoplasm when adipose tissue is incubated in glucose and insulin to be transferred to mitochondria as l-glycerol 3-phosphate or malate. When adipose tissue is incubated in pyruvate alone, reducing power for fatty acid, l-glycerol 3-phosphate and lactate formation may be transferred to the cytoplasm as citrate and malate.

scholarly journals ATP citrate lyase knockdown impacts cancer stem cells in vitro

2013 ◽  
Vol 4 (6) ◽  
pp. e696-e696 ◽  
Author(s):  
J-i Hanai ◽  
N Doro ◽  
P Seth ◽  
V P Sukhatme
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Atp Citrate Lyase ◽  
Citrate Lyase

scholarly journals Impact of a High-fat Diet on Tissue Acyl-CoA and Histone Acetylation Levels

2017 ◽  
Vol 292 (8) ◽  
pp. 3312-3322 ◽  
Author(s):  
Alessandro Carrer ◽  
Joshua L. D. Parris ◽  
Sophie Trefely ◽  
Ryan A. Henry ◽  
David C. Montgomery ◽  
...  
Keyword(s):  
Histone Acetylation ◽  
High Fat Diet ◽  
Cell Types ◽  
High Fat ◽  
Atp Citrate Lyase ◽  
Acetyl Coa ◽  
Citrate Lyase ◽  
Liver And Pancreas ◽  
The Impact

Cellular metabolism dynamically regulates the epigenome via availability of the metabolite substrates of chromatin-modifying enzymes. The impact of diet on the metabolism-epigenome axis is poorly understood but could alter gene expression and influence metabolic health. ATP citrate-lyase produces acetyl-CoA in the nucleus and cytosol and regulates histone acetylation levels in many cell types. Consumption of a high-fat diet (HFD) results in suppression of ATP citrate-lyase levels in tissues such as adipose and liver, but the impact of diet on acetyl-CoA and histone acetylation in these tissues remains unknown. Here we examined the effects of HFD on levels of acyl-CoAs and histone acetylation in mouse white adipose tissue (WAT), liver, and pancreas. We report that mice consuming a HFD have reduced levels of acetyl-CoA and/or acetyl-CoA:CoA ratio in these tissues. In WAT and the pancreas, HFD also impacted the levels of histone acetylation; in particular, histone H3 lysine 23 acetylation was lower in HFD-fed mice. Genetic deletion of Acly in cultured adipocytes also suppressed acetyl-CoA and histone acetylation levels. In the liver, no significant effects on histone acetylation were observed with a HFD despite lower acetyl-CoA levels. Intriguingly, acetylation of several histone lysines correlated with the acetyl-CoA: (iso)butyryl-CoA ratio in liver. Butyryl-CoA and isobutyryl-CoA interacted with the acetyltransferase P300/CBP-associated factor (PCAF) in liver lysates and inhibited its activity in vitro. This study thus provides evidence that diet can impact tissue acyl-CoA and histone acetylation levels and that acetyl-CoA abundance correlates with acetylation of specific histone lysines in WAT but not in the liver.

Regulation of ATP-Citrate Lyase in Rat Adipose Tissue

1986 ◽  
Vol 478 (1 Metabolic Reg) ◽  
pp. 304-306
Author(s):  
SEETHALA RAMAKRISHNA ◽  
WILLIAM B. BENJAMIN
Keyword(s):  
Adipose Tissue ◽  
Atp Citrate Lyase ◽  
Citrate Lyase ◽  
Rat Adipose Tissue

Substrates and inhibitors of ATP: Citrate lyase from adipose tissue

1977 ◽  
Vol 8 (11) ◽  
pp. 773-779
Author(s):  
H.J. Mersmann ◽  
L.J. Brown ◽  
J.M. Houk ◽  
D.R. Rao ◽  
D.G. Steffen
Keyword(s):  
Adipose Tissue ◽  
Atp Citrate Lyase ◽  
Citrate Lyase

scholarly journals Lipid biosynthesis in liver slices of the foetal guinea pig

1976 ◽  
Vol 154 (1) ◽  
pp. 149-158 ◽  
Author(s):  
C T Jones ◽  
I K Ashton
Keyword(s):  
Phosphoenolpyruvate Carboxykinase ◽  
Fatty Acid Synthetase ◽  
Lipid Synthesis ◽  
Short Chain Fatty Acids ◽  
Acetate Incorporation ◽  
Atp Citrate Lyase ◽  
Acetyl Coa ◽  
Citrate Lyase ◽  
Effect Of Glucose

Lipid synthesis as measured by the incorporation of acetate or 3H2O into slices of foetal liver, is much higher than in slices of adult liver and shows a peak at about two-thirds of gestation. At this time the synthesis from glucose was low and reached a peak 10 days later. The changes in the activity of ATP citrate lyase, which mirrored acetate incorporation, and the effect of glucose and pyruvate on acetate corporation into lipid suggests that some of the lipid synthesis occurs via intramitochondrial acetyl-CoA production from acetate. Despite this, lipid synthesis was not inhibited by (-)-hydroxycitrate. The low rate of synthesis from glucose at two-thirds of gestation is ascribed to the low activity of pyruvate carboxylase at this time and a role for a phosphoenolpyruvate carboxykinase in providing oxaloacetate for lipogenesis is proposed. The activity of fatty acid synthetase broadly agreed with the changes in lipid synthesis, whereas the activity of acetyl-CoA carboxylase was barely sufficient to account for the rates of lipid synthesis in vivo. Acetate and short-chain fatty acids are likely to be the major precursors for lipid synthesis in vivo.

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