scholarly journals Ethanol administration and the relationship of malonyl-coenzyme A concentrations to the rate of fatty acid synthesis in rat liver

1973 ◽  
Vol 136 (3) ◽  
pp. 639-647 ◽  
Author(s):  
Robert W. Guynn ◽  
Dulce Veloso ◽  
Raymond L. Harris ◽  
J. W. Randolph Lawson ◽  
Richard L. Veech
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
De Novo ◽  
Fatty Acid Synthetase ◽  
Acid Synthesis ◽  
Ethanol Administration ◽  
Liver Fatty Acid ◽  
Malonyl Coa ◽  
Significant Difference

1. The effect of ethanol on liver fatty acid synthesis was studied in vivo in 24h-starved and ‘meal-fed’ rats (i.e. fed for 3h per day and not ad libitum). 2. In the fed animal3H2O was incorporated into fat at a rate of 0.46μmol of C2 units/min per g wet wt. of liver. Administration of either ethanol (3.2g/kg) or equicaloric amounts of glucose had no effect on the rate of3H2O incorporation into lipid. 3. In the 24h-starved animal, administration of the same dose of ethanol produced an increase in the rate of3H2O incorporation from 0.06 to 0.12μmol of C2 units/min per g fresh wt. after 3h whereas [malonyl-CoA] increased from 0.006 to 0.009μmol/g. Glucose given in amounts equicaloric to ethanol was significantly more lipogenic, increasing both the3H2O incorporation from 0.06 to 0.20μmol of C2 units/min per g and the malonyl-CoA content from 0.006 to 0.013 μmol/g wet wt. at 3h. 4. The decrease in the redox state of free cytoplasm NAD or NADP couples or the changes in content of citrate, glucose 6-phosphate and pyruvate of liver after ethanol administration had no measurable effect on the rate of fatty acid synthesis in vivo. 5. Under the conditions of the experiments there was no significant difference, among any of the groups, in the activity of liver fatty acid synthetase measured in vitro. A double-reciprocal plot of the rate of3H2O incorporation and the total tissue malonyl-CoA concentrations showed a striking relationship. It has been concluded that the rate of fatty acid synthesis in vivo is determined principally by the Vmax. of fatty acid synthetase and the concentration of free malonyl-CoA. 6. It has also been concluded that under the conditions of the present study, the synthesis of fatty acids de novo is unlikely to be an important factor in the increased liver lipid content associated with ethanol administration.

scholarly journals Hepatic lipogenesis in young rats given proteins of different quality

1984 ◽  
Vol 52 (1) ◽  
pp. 131-137 ◽  
Author(s):  
G. R. Herzberg ◽  
Minda Rogerson
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Protein Quality ◽  
Fatty Acid Synthetase ◽  
Acid Synthesis ◽  
Hepatic Lipogenesis ◽  
Atp Citrate Lyase ◽  
Specific Activities ◽  
Glucose 6 Phosphate Dehydrogenase

1. The effect of feeding casein, lactalbumin, soya-bean protein, gluten or gelatin on hepatic lipogenesis and the levels of hepatic fatty acid synthetase (FAS), glucose-6-phosphate dehydrogenase (EC 1. 1. 1.49; G6PD), malic enzyme (EC 1. 1. 1.40; ME) ATP-citrate lyase (EC 4. 1. 3. 8; CL), acetyl CoA carboxylase (EC 6.4.1.2; ACCx) and glucokinase (EC 2. 7. 1. 2; GK) was examined in young growing rats.2. The total activities of ACCx, FAS, CL, GK, G6PD, GK, ME and fatty acid synthesis in vivo were positively correlated with protein quality.3. The specific activities of ACCx, FAS, CL, G6PD and fatty acid synthesis in vivo were positively correlated with protein quality.4. The specific activities of GK and ME were unrelated to protein quality.5. The results demonstrate a dissociation between ME and hepatic lipogenesis and suggest a role for the NADPH generated by ME which is not related to the needs of fatty acid synthesis.

scholarly journals The role of dietary protein in hepatic lipogenesis in the young rat

1981 ◽  
Vol 45 (3) ◽  
pp. 529-538 ◽  
Author(s):  
G. R. Herzberg ◽  
Minda Rogerson
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Dietary Protein ◽  
Fatty Acid Synthetase ◽  
Acid Synthesis ◽  
Hepatic Lipogenesis ◽  
Hepatic Fatty Acid ◽  
Cleavage Enzyme ◽  
Glucose 6 Phosphate Dehydrogenase

1. The effect of varying dietary levels of casein (40–140 g/kg) on hepatic lipogenesis and the levels of hepatic fatty acid synthetase (FAS), glucose-6-phosphate dehydrogenase (EC 1.1.1.49; G6PD), malic enzyme (EC 1.1.1.40; ME), citrate cleavage enzyme (EC 4.1.3.8;CCE), acetyl CoA carboxylase (EC 6.4.1.2; AcCx), glucokinase (EC 2.7.1.2; GK), and pyruvate dehydrogenase (PDH) was examined in young, growing rats.2. The activities of AcCx, FAS, G6PD and in vivo fatty acid synthesis were generally found to increase with increased dietary protein.3. The levels of GK and PDH were not related to dietary protein.4. ME decreased with increasing dietary protein.5. The results demonstrate a dissociation between hepatic fatty acid synthesis and ME and suggest that when rats consume low-protein diets the NADPH needed for fatty acid synthesis is generated primarily by ME but that as the level of dietary protein is increased the contribution of ME is reduced while that of the phosphogluconate pathway becomes more important.

scholarly journals Chronic ethanol administration depresses fatty acid synthesis in rat adipose tissue

1988 ◽  
Vol 251 (2) ◽  
pp. 547-551 ◽  
Author(s):  
J S Wilson ◽  
M A Korsten ◽  
L P Donnelly ◽  
P W Colley ◽  
J B Somer ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Fatty Acid Synthetase ◽  
Acid Synthesis ◽  
Chronic Ethanol ◽  
Ethanol Administration ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa ◽  
Chronic Ethanol Administration

Administration of ethanol as part of a nutritionally adequate liquid diet to female Wistar rats was found to depress markedly incorporation of labelled glucose into adipose-tissue acylglycerol fatty acids. Similar results with labelled pyruvate and acetate suggested inhibition of the fatty-acid-synthesis pathway at, or distal to, the acetyl-CoA carboxylase step. Activities of acetyl-CoA carboxylase and fatty acid synthetase were markedly lower in ethanol-fed animals. The activity of another lipogenic enzyme, phosphatidate phosphohydrolase, was not affected by chronic ethanol feeding. These findings suggest that chronic ethanol administration has marked effects on adipose-tissue lipogenesis.

scholarly journals Regulation of hepatic lipogenesis by dietary maize oil or tripalmitin in the meal-fed mouse

1980 ◽  
Vol 43 (3) ◽  
pp. 571-579 ◽  
Author(s):  
G. R. Herzberg ◽  
N. Janmohamed
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Malic Enzyme ◽  
Fatty Acid Synthetase ◽  
Acid Synthesis ◽  
Hepatic Lipogenesis ◽  
Meal Feeding ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Maize Oil

The effect of varying dietary levels of maize oil and tripalmitin (0–250 g fat/kg) on hepatic lipogenesis and the levels of hepatic fatty acid synthetase (FAS), glucose-6-phosphate dehydrogenase (EC 1.1.1.49; G6PD), malic enzyme (EC 1.1.1.38, 1.1.1.39, 1.1.1.40; ME) and glucokinase (EC 2.7.1.2; GK) was examined in meal-fed mice.2. Meal-fed mice compared to mice fed ad lib. show enhanced hepatic lipogenesis as demonstrated by an increased rate of in vivo fatty acid synthesis and increased levels of FAS, ME and G6PD. The level of GK in meal-fed mice was unchanged by meal feeding.3. Maize oil more effectively reduced in vivo hepatic lipogenesis than tripalmitin in meal-fed mice.4. Maize oil more effectively reduced the hepatic levels of FAS, G6PD, ME and GK than tripalmitin in meal-fed mice.5. The increased inhibition by maize oil is observed at all levels of fat in the diet investigated and has been shown not to be due to decreased carbohydrate intake nor to differences between the absorption of maize oil and tripalmitin.

scholarly journals USP22-dependent accumulation of lipidomes drives hepatocellular carcinoma progression by stabilizing PPARγ

2020 ◽  
Author(s):  
Zhen Ning ◽  
Xin Guo ◽  
Xiaolong Liu ◽  
Chang Lu ◽  
Aman Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Fatty Acid ◽  
Molecular Mechanism ◽  
Fatty Acid Synthesis ◽  
De Novo ◽  
Acid Synthesis ◽  
Specific Protease ◽  
Pparγ Expression

Abstract Elevated de novo lipogenesis (DNL) is considered to be a crucial factor in hepatocellular carcinoma (HCC) development. However, the molecular mechanism for its occurrence in HCC is still unclear. Herein, we identified ubiquitin-specific protease 22 (USP22) as a key regulator for de novo fatty acid synthesis, which directly interacts with, deubiquitinates and stabilizes PPARγ through K48-linked deubiquitination, and in turn, this stabilization increases ACC and ACLY transcription. In addition, we found that USP22 promoted the de novo synthesis of fatty acid labeling from glucose tracers. USP22-dysregulated de novo fatty acid synthesis contributes to HCC progression, but USP22 was functionality suppressed by inhibiting the expression of PPARγ, ACLY, or ACC in in vitro cell proliferation and in vivo tumorigenesis experiments. In HCC, USP22 expression positively correlates with PPARγ expression, and simultaneously, high expression of USP22 and PPARγ or USP22, ACC and ACLY is associated with a poor prognosis. Taken together, we identified a previously undescribed USP22-regulated lipogenesis molecular mechanism that involves the PPARγ-ACLY/ACC axis in HCC tumorigenesis and provide a rationale for therapeutic targeting of lipogenesis via USP22 inhibition.

scholarly journals Localization of chloroplastic fatty acid synthesis de novo in the stroma

1985 ◽  
Vol 226 (2) ◽  
pp. 551-556 ◽  
Author(s):  
K A Walker ◽  
J L Harwood
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
High Speed ◽  
De Novo ◽  
Fatty Acid Synthetase ◽  
Acid Synthesis ◽  
Synthetic Activity ◽  
Bisphosphate Carboxylase ◽  
Osmotic Lysis ◽  
Almost All

The synthesis of fatty acids de novo from [2-14C]malonyl-CoA was studied in fractions from lettuce (Lactuca sativa) and pea (Pisum sativum) chloroplasts. When lettuce chloroplasts were subjected to osmotic lysis, disintegration through a Yeda press and high-speed centrifugation, essentially all of the fatty-acid-synthetic activity was found to be soluble. The distribution of the activity in various chloroplast fractions was similar to that of soluble marker enzymes such as ribulose-1,5-bisphosphate carboxylase and NADP+-linked glyceraldehyde-3-phosphate dehydrogenase. Marked differences were apparent in the quality of products from fatty acid synthesis de novo in the various fractions of chloroplasts. Thus soluble fractions produced predominantly stearate, whereas those containing membranes produced a greater proportion of palmitate. In pea chloroplasts, osmotic lysis released almost all of the fatty acid synthetase into the stromal fraction. In this instance, no major alterations in the products of fatty acid synthesis were observed. The fatty-acid-synthetic activity of the stromal fraction was still soluble after prolonged ultracentrifugation. The results show clearly the soluble nature of fatty acid synthesis de novo in lettuce and pea chloroplasts. Thus fatty acid synthesis measured in microsomal fractions from such plant tissues is not due to the presence of chloroplastic membranes.

scholarly journals Fatty acid synthesis in the perfused liver of adrenalectomized rats

1976 ◽  
Vol 156 (3) ◽  
pp. 593-602 ◽  
Author(s):  
C J Kirk ◽  
T R Verrinder ◽  
D A Hems
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
De Novo ◽  
Direct Action ◽  
Acid Synthesis ◽  
Diabetic Rats ◽  
Perfused Liver ◽  
Control Sham ◽  
Adrenalectomized Rats

1. Fatty acid synthesis, measured in the perfused liver of fed adrenalectomized rats with 3H2O and 14C-labelled precursors, was less than in control sham-operated rats. 2. This defect was more extensive for synthesis of fatty acids incorporated into triacylglycerols than into phospholipids. 3. There was impairment in desaturation and export of newly synthesized fatty acid. 4. Fatty acid synthesis and desaturation were restored to normal rates 5h after treatment with cortisol in vivo. 5. Fatty acid synthesis was seasonally variable, being highest in the winter; the impairment after adrenalectomy was observed in all seasons. 6. In perfusions with oleate (0.7 mM), no further impairment in fatty acid synthesis was discerned in livers from adrenalectomized rats, in which the rate resembled that in control livers. 7. No defect in the incorporation of oleate into glycerides was discerned in livers from adrenalectomized rats. 8. Cortisol exerted no stimulatory effect on fatty acid synthesis when added to perfusion media. 9. The impairment in hepatic lipogenesis, demonstrable after adrenalectomy, shows that adrenal glucocorticoids promote hepatic capacity for fatty acid synthesis de novo, at least in intact non-diabetic rats. It is suggested that this effect is mediated by insulin, perhaps through direct action on the liver.

scholarly journals Fatty acid elongation by a particulate fraction from germinating pea

1980 ◽  
Vol 191 (3) ◽  
pp. 791-797 ◽  
Author(s):  
B R Jordan ◽  
J L Harwood
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
High Speed ◽  
Saturated Fatty Acids ◽  
Acyl Chain ◽  
Fatty Acid Synthetase ◽  
Acid Synthesis ◽  
Particulate Fraction

The synthesis of fatty acids from [14C]malonyl-CoA was studied with a high-speed particulate fraction from germinating pea (Pisum sativum). The variety used (Feltham First) produced mainly saturated fatty acids with palmitate (30–40%) and stearate (40–60%) predominating. Several palmitate-containing lipids stimulated overall synthesis and, in addition, increased the percentage of label in stearate. The production of stearate was severely inhibited by preincubation of the microsomal fraction with snake venom phospholipase A2 or by incubation with Rhizopus arrhizus lipase. Addition of a series of di-saturated phosphatidylcholines, with different acyl constituents, resulted in stimulation of overall fatty acid synthesis as well as an increase in the radiolabelling of the fatty acid two carbon atoms longer than the acyl chain added. This chain lengthening of fatty acids donated from phosphatidylcholine was due to the action of both fatty acid synthetase and palmitate elongase. The latter would utilize dipalmitoyl phosphatidylcholine and was sensitive to arsenite whereas fatty acid synthetase would use dilauroyl phosphatidylcholine and was sensitive to cerulenin. The results are discussed in relation to previous data obtained in vivo on plant fatty acid synthesis and current suggestions for the role of phosphatidylcholine in this process.

scholarly journals The effect of chronic ethanol administration on lipogenesis in liver and adipose tissue in the rat

1983 ◽  
Vol 50 (3) ◽  
pp. 549-553 ◽  
Author(s):  
Carmen Cascales ◽  
Manuel Benito ◽  
María Cascales ◽  
Trinidad Caldés ◽  
Angel Santos-Ruiz
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
De Novo ◽  
Tritiated Water ◽  
Acid Synthesis ◽  
Male Rats ◽  
Ethanol Administration ◽  
Chronic Ethanol Administration ◽  
Food And Drink

1. Rates of lipogenesis de novo have been studied in liver and epididymal fat pads of male rats chronically treated with ethanol. A solution of ethanol (150 ml/l) was administered as the only drinking fluid for 3 months with a standard solid diet; both food and drink were available ad lib.2. Lipogenesis in vivo was measured by the incorporation of tritiated water into lipid fractions: non-saponifiable lipid and fatty acids. Non-saponifiable lipid, both in liver and in adipose tissue, was unaffected by ethanol treatment. However, fatty acid synthesis de novo was significantly enhanced in both liver and adipose tissue, by 150 and 300% respectively.3. Plasma triacylglycerol and non-esterified fatty acid levels were unchanged and plasma glucose concentration slightly increased by ethanol administration.4. The rate of lipogenesis increased when insulin: glucagon increased twofold due to the effect of ethanol.

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