Depressed lipogenesis induced by cold stress

1960 ◽  
Vol 199 (3) ◽  
pp. 449-452 ◽  
Author(s):  
E. J. Masoro
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Cold Stress ◽  
Carbohydrate Metabolism ◽  
Liver Cells ◽  
Hexose Monophosphate ◽  
Hexose Monophosphate Pathway ◽  
Liver Homogenates ◽  
Fasted Rats ◽  
Low Rate

Liver homogenates were prepared from control, cold-fed and cold-fasted rats. Homogenates from control and cold-fed rats synthesized fatty acids to about the same extent. However, homogenates from cold-fasted rats converted far less acetate-1-C14 to fatty acids than homogenates from control and cold-fed rats. Previous studies showed that lipogenesis is depressed in liver slices from both cold-fed and cold-fasted rats. Probably the fact that lipogenesis is inhibited in the intact liver cells of cold-fed rats is not the result of reduced levels of fatty acid-synthesizing enzymes but is the result of an unfavorable cofactor environment; the evidence indicates that a low rate of TPNH generation via the hexose monophosphate pathway of carbohydrate metabolism causes the reduction in lipogenic activity. The failure in lipogenesis in the liver cells of the cold-fasted rat appears to result from quite a different cause than that of the cold-fed rat. The most likely reason for the low rate of lipogenesis in the liver of cold-fasted rats appears to be the loss of the fatty acid-synthesizing enzymes; however, the possibility that this lipogenic defect is related to the lack of a cofactor—as yet undiscovered— cannot be discounted.

EFFECT OF ALLOXAN, INSULIN, AND THYROXINE ON CHOLESTEROL AND FATTY ACID SYNTHESIS BY RAT LIVER HOMOGENATES

1957 ◽  
Vol 35 (1) ◽  
pp. 15-23 ◽  
Author(s):  
J. F. Scaife ◽  
B. B. Migicovsky
Keyword(s):  
Carbon Dioxide ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Rat Liver ◽  
Fatty Acid Synthesis ◽  
Sodium Acetate ◽  
Cholesterol Synthesis ◽  
Acid Synthesis ◽  
Liver Homogenates ◽  
Vitro Effect

The in vitro effect of alloxan and insulin on the synthesis of cholesterol and fatty acids from 1-C14-sodium acetate by rat liver homogenates has been examined. Alloxan caused a reduction in the incorporation of acetate into cholesterol, fatty acids, and C14O2, but an increase in the oxygen consumption and carbon dioxide production. The addition of insulin to homogenates caused a reduction in cholesterol synthesis but an increase in fatty acid synthesis both for normal and diabetic animals. Homogenates from thyrotoxic rats exhibited a marked reduction in cholesterol synthesis when compared with normal animals. C14O2 production by homogenates from starved rats was appreciably lower than for those from normal animals. With this exception no appreciable difference was found in the oxygen uptake, carbon dioxide, or C14O2 production in homogenates from normal, starved, thyroxine-treated, or diabetic animals. Synthesized cholesterol was found to be located principally in the particulate matter of the homogenates after they had been incubated with 1-C14-sodium acetate. Homogenates from starved rats showed no greater tendency to degrade preformed cholesterol during incubation than did those from normal rats.

scholarly journals The regulation of triglyceride synthesis and fatty acid synthesis in rat epididymal adipose tissue. Effects of insulin, adrenaline and some metabolites in vitro

1970 ◽  
Vol 119 (2) ◽  
pp. 193-219 ◽  
Author(s):  
E. D. Saggerson ◽  
A. L. Greenbaum
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Acid Synthesis ◽  
Fatty Acyl ◽  
Mass Action ◽  
Hexose Monophosphate ◽  
Tissue Concentrations ◽  
Hexose Monophosphate Pathway ◽  
Long Chain

1. Adipose tissues from rats fed a balanced diet were incubated in the presence of glucose (20mm) with the following additions: insulin, anti-insulin serum, insulin+acetate, insulin+pyruvate, insulin+lactate, insulin+phenazine methosulphate, insulin+oleate+albumin, insulin+adrenaline+albumin, insulin+6-N-2′-O-dibutyryl 3′:5′-cyclic AMP+albumin. 2. Measurements were made of the whole tissue concentrations of adenine nucleotides, hexose phosphates, triose phosphates, glycerol 1-phosphate, 3 phosphoglycerate, 6-phosphogluconate, long-chain fatty acyl-CoA, acid-soluble CoA, citrate, isocitrate, malate and 2-oxoglutarate, and of the release into the incubation medium of lactate, pyruvate and glycerol after 1h of incubation. 3. Fluxes of [14C]glucose carbon through the major pathways of glucose metabolism were calculated from the yields of 14C in various products after 2h of incubation. Fluxes of [14C]acetate, [14C]pyruvate or [14C]lactate carbon in the presence of glucose were also determined. 4. Measurements were also made of the whole-tissue concentrations of metabolites in tissues taken directly from Nembutal-anaesthetized rats. 5. Whole tissue mass-action ratios for phosphofructokinase, phosphoglucose isomerase and the combined (aldolase×triose phosphate isomerase) reaction were similar in vivo and in vitro. The reactants of phosphofructokinase appeared to be far from mass-action equilibrium. In vitro, the reactants of hexokinase also appeared to be far from mass-action equilibrium. 6. Correlation of observed changes in glycolytic flux with changes in fructose 6-phosphate concentration suggested that phosphofructokinase may show regulatory behaviour. The enzyme appeared to be activated in the presence of oleate or adrenaline and to be inhibited in the presence of lactate or pyruvate. 7. Evidence is presented that the reactants of lactate dehydrogenase and glycerol 1-phosphate dehydrogenase may be near to mass-action equilibrium in the cytoplasm. 8. No satisfactory correlations could be drawn between the whole-tissue concentrations of long-chain fatty acyl-CoA, citrate and glycerol 1-phosphate and the observed rates of triglyceride and fatty acid synthesis. Under the conditions employed, the concentration of glycerol 1-phosphate appeared to depend mainly on the cytoplasmic [NAD+]/[NADH] ratios. 9. Calculated hexose monophosphate pathway flux rates roughly correlated with fatty acid synthesis rates and with whole tissue [6-phosphogluconate]/[glucose 6-phosphate] ratios. The relative rates of production of NADPH for fatty acid synthesis by the hexose monophosphate pathway and by the `malic enzyme' are discussed. It is suggested that all NADH produced in the cytoplasm may be used in that compartment for reductive synthesis of fatty acids, lactate or glycerol 1-phosphate.

scholarly journals Peroxisome-proliferator-activated receptor-α (PPARα) deficiency leads to dysregulation of hepatic lipid and carbohydrate metabolism by fatty acids and insulin

2002 ◽  
Vol 364 (2) ◽  
pp. 361-368 ◽  
Author(s):  
Mary C. SUGDEN ◽  
Karen BULMER ◽  
Geoffrey F. GIBBONS ◽  
Brian L. KNIGHT ◽  
Mark J. HOLNESS
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Carbohydrate Metabolism ◽  
Plasma Insulin ◽  
Hepatic Glycogen ◽  
Peroxisome Proliferator ◽  
Hepatic Lipogenesis ◽  
Wild Type ◽  
Peroxisome Proliferator Activated Receptor ◽  
Hepatic Lipid

The aim of the present study was to determine whether peroxisome-proliferator-activated receptor-α (PPARα) deficiency disrupts the normal regulation of triacylglycerol (TAG) accumulation, hepatic lipogenesis and glycogenesis by fatty acids and insulin using PPARα-null mice. In wild-type mice, hepatic TAG concentrations increased (P<0.01) with fasting (24h), with substantial reversal after refeeding (6h). Hepatic TAG levels in fed PPARα-null mice were 2.4-fold higher than in the wild-type (P<0.05), increased with fasting, but remained elevated after refeeding. PPARα deficiency also impaired hepatic glycogen repletion (P<0.001), despite normal insulin and glucose levels after refeeding. Higher levels of plasma insulin were required to support similar levels of hepatic lipogenesis de novo (3H2O incorporation) in the PPARα-null mice compared with the wild-type. This difference was reflected by corresponding changes in the relationship between plasma insulin and the mRNA expression of the lipogenic transcription factor sterol-regulatory-element-binding protein-1c, and that of one of its known targets, fatty acid synthase. In wild-type mice, hepatic pyruvate dehydrogenase kinase (PDK) 4 protein expression (a downstream marker of altered fatty acid catabolism) increased (P<0.01) in response to fasting, with suppression (P<0.001) by refeeding. Although PDK4 up-regulation after fasting was halved by PPARα deficiency, PDK4 suppression after refeeding was attenuated. In summary, PPARα deficiency leads to accumulation of hepatic TAG and elicits dysregulation of hepatic lipid and carbohydrate metabolism, emphasizing the importance of precise control of lipid oxidation for hepatic fuel homoeostasis.

EFFECT OF ALLOXAN, INSULIN, AND THYROXINE ON CHOLESTEROL AND FATTY ACID SYNTHESIS BY RAT LIVER HOMOGENATES

1957 ◽  
Vol 35 (1) ◽  
pp. 15-23 ◽  
Author(s):  
J. F. Scaife ◽  
B. B. Migicovsky
Keyword(s):  
Carbon Dioxide ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Rat Liver ◽  
Fatty Acid Synthesis ◽  
Sodium Acetate ◽  
Cholesterol Synthesis ◽  
Acid Synthesis ◽  
Liver Homogenates ◽  
Vitro Effect

The in vitro effect of alloxan and insulin on the synthesis of cholesterol and fatty acids from 1-C14-sodium acetate by rat liver homogenates has been examined. Alloxan caused a reduction in the incorporation of acetate into cholesterol, fatty acids, and C14O2, but an increase in the oxygen consumption and carbon dioxide production. The addition of insulin to homogenates caused a reduction in cholesterol synthesis but an increase in fatty acid synthesis both for normal and diabetic animals. Homogenates from thyrotoxic rats exhibited a marked reduction in cholesterol synthesis when compared with normal animals. C14O2 production by homogenates from starved rats was appreciably lower than for those from normal animals. With this exception no appreciable difference was found in the oxygen uptake, carbon dioxide, or C14O2 production in homogenates from normal, starved, thyroxine-treated, or diabetic animals. Synthesized cholesterol was found to be located principally in the particulate matter of the homogenates after they had been incubated with 1-C14-sodium acetate. Homogenates from starved rats showed no greater tendency to degrade preformed cholesterol during incubation than did those from normal rats.

FATTY ACID, CHOLESTEROL, AND ACETOACETATE BIOSYNTHESIS IN LIVER HOMOGENATES FROM NORMAL AND STARVED GUINEA PIGS

1960 ◽  
Vol 38 (1) ◽  
pp. 635-641
Author(s):  
Frank Sauer
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Guinea Pigs ◽  
Liver Homogenates ◽  
In Vitro Biosynthesis

Fatty acid, cholesterol, and acetoacetate biosynthesis was studied with liver homogenates from normal and starved guinea pigs. Starvation suppressed the incorporation of acetate into fatty acids and cholesterol but not into acetoacetate. The in vitro biosynthesis of cholesterol and fatty acids was not restored by the addition of either G-6-P or isocitrate in combination with TPN, nor was it restored by orally dosing the starved animals with dextrose. The addition of isocitrate to normal homogenates depressed cholesterogenesis and stimulated lipogenesis.

FATTY ACID, CHOLESTEROL, AND ACETOACETATE BIOSYNTHESIS IN LIVER HOMOGENATES FROM NORMAL AND STARVED GUINEA PIGS

1960 ◽  
Vol 38 (7) ◽  
pp. 635-641 ◽  
Author(s):  
Frank Sauer
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Guinea Pigs ◽  
Liver Homogenates ◽  
In Vitro Biosynthesis

Fatty acid, cholesterol, and acetoacetate biosynthesis was studied with liver homogenates from normal and starved guinea pigs. Starvation suppressed the incorporation of acetate into fatty acids and cholesterol but not into acetoacetate. The in vitro biosynthesis of cholesterol and fatty acids was not restored by the addition of either G-6-P or isocitrate in combination with TPN, nor was it restored by orally dosing the starved animals with dextrose. The addition of isocitrate to normal homogenates depressed cholesterogenesis and stimulated lipogenesis.

Synthesis of Unsaturated Fatty Acids in Chick Embryo Liver

1971 ◽  
Vol 49 (5) ◽  
pp. 563-567 ◽  
Author(s):  
W. E. Donaldson ◽  
Nancy S. Mueller
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Unsaturated Fatty Acids ◽  
De Novo ◽  
Saturated Fatty Acids ◽  
Acid Synthesis ◽  
Chick Embryos ◽  
Embryo Liver ◽  
Liver Homogenates ◽  
Cyclopropene Fatty Acids

Oxidation, synthesis, and desaturation of fatty acids were assessed in chick embryos and embryonic liver. No differences in the oxidation of palmitate-1-14C and oleate-1-14C by intact embryos and embryo-liver homogenates were found. De novo fatty acid synthesis and microsomal elongation of fatty acids were detected in embryo-liver homogenates, but the activities were low as compared with chick liver. The specific activities of the mitochondrial system of fatty acid elongation were similar in embryo and chick liver. Stimulation of the desaturation of stearic acid was achieved by the substitution of glucose for fatty acids in the culture medium and abolished by the addition of cyclopropene fatty acids to the medium. The hypothesis is advanced that in chick embryos, the rate of desaturation of fatty acids synthesized de novo is less than that of postembryonic liver, and that as a consequence, the liver of embryos cannot maintain the proportion of unsaturated to saturated fatty acids found in yolk.

Probing metabolic memory in the hepatic response to fasting

2020 ◽  
Vol 52 (12) ◽  
pp. 602-617
Author(s):  
Merel Defour ◽  
Guido J. E. J. Hooiveld ◽  
Michel van Weeghel ◽  
Sander Kersten
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Human Liver ◽  
Tca Cycle ◽  
Liver Glycogen ◽  
Acid Synthesis ◽  
Liver Cells ◽  
Metabolic Memory ◽  
Human Liver Cells ◽  
Glucose Plasma

Tissues may respond differently to a particular stimulus if they have been previously exposed to that same stimulus. Here, we tested the hypothesis that a strong metabolic stimulus such as fasting may influence the hepatic response to a subsequent fast and thus elicit a memory effect. Overnight fasting in mice significantly increased plasma free fatty acids, glycerol, β-hydroxybutyrate, and liver triglycerides, and decreased plasma glucose, plasma triglycerides, and liver glycogen levels. In addition, fasting dramatically changed the liver transcriptome, upregulating genes involved in gluconeogenesis and in uptake, oxidation, storage, and mobilization of fatty acids, and downregulating genes involved in fatty acid synthesis, fatty acid elongation/desaturation, and cholesterol synthesis. Fasting also markedly impacted the liver metabolome, causing a decrease in the levels of numerous amino acids, glycolytic-intermediates, TCA cycle intermediates, and nucleotides. However, these fasting-induced changes were unaffected by two previous overnight fasts. Also, no significant effect was observed of prior fasting on glucose tolerance. Finally, analysis of the effect of fasting on the transcriptome in hepatocyte humanized mouse livers indicated modest similarity in gene regulation in mouse and human liver cells. In general, genes involved in metabolic pathways were upregulated or downregulated to a lesser extent in human liver cells than in mouse liver cells. In conclusion, we found that previous exposure to fasting in mice did not influence the hepatic response to a subsequent fast, arguing against the concept of metabolic memory in the liver. Our data provide a useful resource for the study of liver metabolism during fasting.

FATTY ACID INHIBITION OF CHOLESTEROL SYNTHESIS

1956 ◽  
Vol 34 (1) ◽  
pp. 861-868 ◽  
Author(s):  
J. D. Wood ◽  
B. B. Migicovsky
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Chain Length ◽  
Rat Liver ◽  
Cholesterol Synthesis ◽  
Rapid Decrease ◽  
Acid Inhibition ◽  
Degree Of Unsaturation ◽  
Liver Homogenates ◽  
Fatty Acid Inhibition

Fatty acids inhibit cholesterol synthesis by rat liver homogenates. Inhibition occurs with acids containing either an even or an odd number of carbon atoms in the chain, and with saturated and unsaturated acids, the inhibition increasing with the degree of unsaturation of the acid. In the case of acids with an even number of carbon atoms the inhibition increases with chain length to a maximum at 12 carbons after which a rapid decrease occurs. The presence of fatty acid during cholesterol synthesis increases the acetate incorporated into fatty acids to a slight extent. This increase is small compared with the decrease in the amount incorporated into cholesterol. A possible mechanism for the inhibition is discussed.

scholarly journals The effect of starvation and starvation followed by feeding on enzyme activity and the metabolism of [U−14C]glucose in liver from growing chicks

1968 ◽  
Vol 108 (4) ◽  
pp. 667-673 ◽  
Author(s):  
Alan G. Goodridge
Keyword(s):  
Fatty Acids ◽  
Enzyme Activity ◽  
Fatty Acid ◽  
Isocitrate Dehydrogenase ◽  
Malic Enzyme ◽  
Acid Synthesis ◽  
Minor Role ◽  
Hexose Monophosphate ◽  
Hexose Monophosphate Shunt ◽  
Cleavage Enzyme

1. The conversion of [U−14C]glucose into carbon dioxide, cholesterol and fatty acids in liver slices and the activities of ‘malic’ enzyme, citrate-cleavage enzyme, NADP-linked isocitrate dehydrogenase and hexose monophosphate-shunt dehydrogenases in the soluble fraction of homogenates of liver were measured in chicks that were starved or starved then fed. 2. In newly hatched chicks the incorporation of [U−14C]glucose and the activity of ‘malic’ enzyme did not increase unless the birds were fed. The response to feeding of [U−14C]glucose incorporation into fatty acids increased as the starved chicks grew older. 3. Citrate-cleavage enzyme activity increased slowly even when the newly hatched chicks were unfed. On feeding, citrate-cleavage enzyme activity increased at a much faster rate. 4. In normally fed 20-day-old chicks starvation decreased the incorporation of [U−14C]glucose into all three end products and depressed the activities of ‘malic’ enzyme and citrate-cleavage enzyme. Re-feeding increased all of these processes to normal or higher-than-normal levels. 5. In both newly hatched and 20-day-old chicks starvation increased the activity of isocitrate dehydrogenase and feeding or re-feeding decreased it. 6. Very little change in hexose monophosphate-shunt dehydrogenase activity was observed during the dietary manipulations. 7. The results indicate that increased substrate delivery to the liver is the principal stimulus to the increased rate of glucose metabolism observed in newly hatched chicks. The results also suggest that changes in the activities of ‘malic’ enzyme and citrate-cleavage enzyme are secondary to an increased flow of metabolites through the glucose-to-fatty acid pathway and that the dehydrogenases of the hexose monophosphate shunt play a minor role in NADPH production for fatty acid synthesis.

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