scholarly journals The control of fatty acid and triglyceride synthesis in rat epididymal adipose tissue. Roles of coenzyme A derivatives, citrate and l-glycerol 3-phosphate

1968 ◽  
Vol 110 (1) ◽  
pp. 27-38 ◽  
Author(s):  
R M Denton ◽  
M L Halperin
Keyword(s):  
Fatty Acid ◽  
Acid Synthesis ◽  
Fatty Acyl ◽  
Epididymal Adipose Tissue ◽  
Total Acid ◽  
Tissue Concentrations ◽  
Acetyl Coa ◽  
Triglyceride Synthesis ◽  
Fat Pads

1. Methods are described for the extraction and assay of acetyl-CoA and of total acid-soluble and total acid-insoluble CoA derivatives in rat epididymal adipose tissue. 2. The concentration ranges of the CoA derivatives in fat pads incubated in vitro under various conditions were: total acid-soluble CoA, 0·20–0·59mm; total acid-insoluble CoA, 0·08–0·23mm; acetyl-CoA, 0·03–0·14mm. 3. An investigation was made of some postulated mechanisms of control of fatty acid and triglyceride synthesis in rat epididymal fat pads incubated in vitro. The concentrations of intermediates of possible regulatory significance were measured at various rates of fatty acid and triglyceride synthesis produced by the addition to the incubation medium (Krebs bicarbonate buffer containing glucose) of insulin, adrenaline, albumin, palmitate or acetate. 4. The whole-tissue concentrations of glucose 6-phosphate, l-glycerol 3-phosphate, citrate, acetyl-CoA, total acid-soluble CoA and total acid-insoluble CoA were assayed after 30 or 60min. incubation. The rates of fatty acid and triglyceride synthesis, calculated from the incorporation of [U−14C]glucose into fatty acids and glyceride glycerol respectively, and the rates of glucose uptake, lactate plus pyruvate output and glycerol output were measured over a 60min. incubation. 5. The rate of triglyceride synthesis could not be correlated with the concentrations of either l-glycerol 3-phosphate or long-chain fatty acyl-CoA (measured as total acid-insoluble CoA). Factor(s) other than the whole-tissue concentrations of these recognized precursors appear to be involved in the determination of the rate of triglyceride synthesis. 6. No relationship was found between the rate of fatty acid synthesis and the whole-tissue concentrations of the intermediates, citrate or acetyl-CoA, or with the two proposed effectors of acetyl-CoA carboxylase, citrate (as activator) or long-chain fatty acyl-CoA (as inhibitor). The control of fatty acid synthesis appears to reside in additional or alternative factors.

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.

LIPOGENESIS IN ADIPOSE TISSUE OF MEAL-FED RATS: A POSSIBLE REGULATORY ROLE OF α-GLYCEROPHOSPHATE FORMATION

1967 ◽  
Vol 45 (2) ◽  
pp. 201-214 ◽  
Author(s):  
Gilbert A. Leveille
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Incubation Medium ◽  
Control Mechanism ◽  
Acid Synthesis ◽  
Fatty Acyl ◽  
Epididymal Adipose Tissue ◽  
Malic Dehydrogenase

The incorporation of acetate-1-14C into fatty acids by isolated epididymal adipose tissue of fed and fasted rats adapted to a single daily 2-hour meal (meal eaters) or fed ad libitum (nibblers) was investigated. Fasting (22 hours) markedly depressed lipogenesis whereas fatty acid synthesis increased linearly with time of refeeding in meal-fed but not in nibbling rats. The activities of glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and NADP-malic dehydrogenase in adipose tissue of meal-fed or nibbling rats were not altered as a consequence of a 22-hour fast or of subsequent feeding for 2 hours. The incorporation of acetate-1-l4C into fatty acids by adipose tissue of fasted meal-eating or nibbling animals was markedly enhanced by the addition of unlabeled pyruvate or oxaloacetate to the incubation medium. This stimulatory effect was not observed with adipose tissue front fed meal-eating rats. The addition of unlabeled glucose and insulin to the incubation medium markedly enhanced acetate-1-14C incorporation into fatty acids by isolated adipose tissue and completely overcame any effect of fasting. Adipose tissue converted pyruvate-1-14C, -2-14C, or -3-14C to fatty acids and glyceride-glycerol. The results obtained are consistent with the functioning of a pathway in adipose tissue involving mitochondrial carboxylation of pyruvate to oxaloacetate, and equilibration of the newly formed oxaloacetate with malate and fumarate, followed by cytoplasmic conversion of oxaloacetate to phosphoenol pyruvate. The data are interpreted to support a control mechanism in which fatty acid synthesis is inhibited by tissue fatty acids and fatty acyl-CoA derivatives. The inhibition could in turn be reduced by the availability of α-glycerophosphate, for the esterification of fatty acids. This control mechanism is proposed as the explanation for the refeeding response observed in adipose tissue of meal-fed rats.

scholarly journals Staphylococcus aureus Fatty Acid Auxotrophs Do Not Proliferate in Mice

2013 ◽  
Vol 57 (11) ◽  
pp. 5729-5732 ◽  
Author(s):  
Joshua B. Parsons ◽  
Matthew W. Frank ◽  
Jason W. Rosch ◽  
Charles O. Rock
Keyword(s):  
Fatty Acids ◽  
Staphylococcus Aureus ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Normal Growth ◽  
Acid Synthesis ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa ◽  
Content Type

ABSTRACTInactivation of acetyl-coenzyme A (acetyl-CoA) carboxylase confers resistance to fatty acid synthesis inhibitors inStaphylococcus aureuson media supplemented with fatty acids. The addition ofanteiso-fatty acids (1 mM) plus lipoic acid supports normal growth of ΔaccDstrains, but supplementation with mammalian fatty acids was less efficient. Mice infected with strain RN6930 developed bacteremia, but bacteria were not detected in mice infected with its ΔaccDderivative.S. aureusbacteria lacking acetyl-CoA carboxylase can be propagatedin vitrobut were unable to proliferate in mice, suggesting that the acquisition of inactivating mutations in this enzyme is not a mechanism for the evasion of fatty acid synthesis inhibitors.

scholarly journals The regulation of triglyceride synthesis and fatty acid synthesis in rat epididymal adipose tissue. Effects of altered dietary and hormonal conditions

1970 ◽  
Vol 119 (2) ◽  
pp. 221-242 ◽  
Author(s):  
E. D. Saggerson ◽  
A. L. Greenbaum
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Fatty Acid Synthetase ◽  
Acid Synthesis ◽  
Fatty Acyl ◽  
Acetyl Coa Carboxylase ◽  
Tissue Concentrations ◽  
Adipose Tissues ◽  
Long Chain

1. Epididymal adipose tissues obtained from rats that had been previously starved, starved and refed a high fat diet for 72h, starved and refed bread for 144h or fed a normal diet were incubated in the presence of insulin+glucose or insulin+glucose+acetate. 2. Measurements were made of the whole-tissue concentrations of hexose phosphates, triose phosphates, glycerol 1-phosphate, 3-phosphoglycerate, 6-phosphogluconate, adenine nucleotides, acid-soluble CoA, long-chain fatty acyl-CoA, malate and citrate after 1h of incubation. The release of lactate, pyruvate and glycerol into the incubation medium during this period was also determined. 3. The rates of metabolism of glucose in the hexose monophosphate pathway, the glycolytic pathway, the citric acid cycle and into glyceride glycerol, fatty acids and lactate+pyruvate were also determined over a 2h period in similarly treated tissues. The metabolism of acetate to CO2 and fatty acids in the presence of glucose was also measured. 4. The activities of acetyl-CoA carboxylase, fatty acid synthetase and isocitrate dehydrogenase were determined in adipose tissues from starved, starved and fat-refed, and alloxan-diabetic animals and also in tissues from animals that had been starved and refed bread for up to 96h. Changes in these activities were compared with the ability of similar tissues to incorporate [14C]glucose into fatty acids in vitro. 5. The activities of acetyl-CoA carboxylase and fatty acid synthetase roughly paralleled the ability of tissues to incorporate glucose into fatty acids. 6. Rates of triglyceride synthesis and fatty acid synthesis could not be correlated with tissue concentrations of long-chain fatty acyl-CoA, citrate or glycerol 1-phosphate. In some cases changes in phosphofructokinase flux rates could be correlated with changes in citrate concentration. 7. The main lesion in fatty acid synthesis in tissues from starved, starved and fat-refed, and alloxan-diabetic rats appeared to reside at the level of pyruvate utilization and to be related to the rate of endogenous lipolysis. 8. It is suggested that pyruvate utilization by the tissue may be regulated by the metabolism of fatty acids within the tissue. The significance of this in directing glucose utilization away from fatty acid synthesis and into glyceride-glycerol synthesis is discussed.

Mammalian fatty acid synthetase. III. Characterization of human liver synthetase products and kinetics of methylmalonyl-CoA inhibition

1976 ◽  
Vol 54 (11) ◽  
pp. 923-926 ◽  
Author(s):  
Daniel A. K. Roncari ◽  
Esther Y. W. Mack
Keyword(s):  
Fatty Acid ◽  
Human Liver ◽  
Fatty Acid Synthetase ◽  
Acid Synthesis ◽  
Acetyl Coa ◽  
Malonyl Coa ◽  
Direct Explanation ◽  
Vitro Model

When propionyl-CoA was substituted for either acetyl-CoA or butyryl-CoA in the presence of [14C]malonyl-CoA and NADPH, the pure human liver fatty acid synthetase complex synthesized only straight-chain, saturated, 15- and 17-carbon radioactive fatty acids. At optimal concentrations, propionyl-CoA was a better primer of fatty acid synthesis than acetyl-CoA. Methylmalonyl-CoA inhibited the synthetase competitively with respect to malonyl-CoA. The Ki was calculated to be 8.4 μM. These findings provide an in vitro model and offer a direct explanation at the molecular level for some of the abnormal manifestations observed in diseases characterized by increased cellular concentrations of propionyl-CoA and methylmalonyl-CoA.

An additional role for insulin in the control of fatty acid synthesis independent of glucose transport

1970 ◽  
Vol 48 (11) ◽  
pp. 1228-1233 ◽  
Author(s):  
M. L. Halperin
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Glucose Transport ◽  
Fatty Acid Synthesis ◽  
Incubation Medium ◽  
Fold Increase ◽  
Acid Synthesis ◽  
Epididymal Adipose Tissue ◽  
Exogenous Substrate

Glucose conversion into pyruvate and fatty acids was studied in epididymal adipose tissue incubated in vitro from normal, 36-h-fasted and fasted–refed rats.Insulin at optimal concentrations caused a 30-fold increase in the rate of glucose incorporation into fatty acids and an increased lactate/pyruvate output rate. Pyruvate, lactate, and N,N,N′,N′,-tetramethyl-p-phenylenediamine (TMPD) addition to this incubation medium resulted in a further 20–75% increase in the rate of fatty acid synthesis as well as a further increase in the pyruvate concentration of the incubation medium. These results suggested that it was the decreased pyruvate concentration secondary to the elevated NADH/NAD+ of the cytoplasm which limited further glucose conversion to fatty acid.With glucose as substrate, TMPD caused the medium pyruvate concentration to be at least as high or higher than that seen with insulin in both nutritional states. However, fatty acid synthesis rates were eightfold greater with insulin. Insulin in the absence of glucose caused a twofold increase in the fatty acid synthesis from pyruvate at a medium concentration of 250 μM in normal and 25 mM in the 36-h-fasted rat. Therefore, insulin augments the rate of fatty acid synthesis both by increasing the supply of substrate (pyruvate) and also by directly increasing pyruvate incorporation into fatty acid by a mechanism distinct from the known stimulation of glucose transport.In fat pads from fasted–refed rats incubated in the absence of exogenous substrate, the rate of fatty acid synthesis was doubled by insulin. This occurred when the rate of pyruvate output was half that in the control condition. This also suggests that insulin stimulated pyruvate conversion to fatty acid in the absence of the known augmentation of glucose transport by insulin.

scholarly journals Aspects of adipose-tissue metabolism in foetal lambs

1981 ◽  
Vol 196 (3) ◽  
pp. 819-824 ◽  
Author(s):  
R G Vernon ◽  
J P Robertson ◽  
R A Clegg ◽  
D J Flint
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Lipoprotein Lipase ◽  
Fatty Acid Synthesis ◽  
Fatty Acid Synthetase ◽  
Acid Synthesis ◽  
Acetyl Coa ◽  
Perirenal Adipose Tissue ◽  
Glycerol Synthesis

1. The mean volume of adipocytes, the rates of fatty acid and acylglycerol glycerol synthesis from various precursors (in vitro), the rates of oxidation of acetate and glucose (in vitro) and the activities of lipoprotein lipase and various lipogenic enzymes were determined for perirenal adipose tissue from foetal lambs during the last month of gestation. 2. The fall in the rate of growth of perirenal adipose tissue during the last month of gestation is associated with a diminished capacity for fatty acid synthesis and lipoprotein lipase activity, but no change in the rate of acylglycerol glycerol synthesis was observed. There was no fall in the activities of cytosolic acetyl-CoA synthetase or the NADP-linked dehydrogenases, suggesting that the decrease in the rate of fatty acid synthesis was due to an impairment at the level of acetyl-CoA carboxylase or fatty acid synthetase. 3. The rate of fatty acid synthesis from acetate was greater than that from glucose. The rate of fatty acid synthesis from glucose per adipocyte of foetal lambs was similar to that of young sheep. The characteristic metabolism of adipose tissue of the adult sheep is thus present in the foetus, despite the relatively large amounts of glucose in the foetal ‘diet’.

scholarly journals Acute effects in vivo of anti-insulin serum on rates of fatty acid synthesis and activities of acetyl-coenzyme A carboxylase and pyruvate dehydrogenase in liver and epididymal adipose tissue of fed rats

1976 ◽  
Vol 160 (2) ◽  
pp. 413-416 ◽  
Author(s):  
D Stansbie ◽  
R W Brownsey ◽  
M Crettaz ◽  
R M Denton
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Pyruvate Dehydrogenase ◽  
Acid Synthesis ◽  
Epididymal Adipose Tissue ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa ◽  
Carboxylase Activity

Plasma insulin concentrations in fed rats were altered acutely by administration of glucose or anti-insulin serum. Rates of fatty acid synthesis in adipose tissue and liver were estimated from the incorporation of 3H from 3H2O. In the adipose tissue dehydrogenase and acetyl-CoA carboxylase were evident. In liver, although changes in rates of fatty acid synthesis were found, the initial activity of pyruvate dehydrogenase did not alter, but small parallel changes in acetyl-CoA carboxylase activity were observed.

Apoprotein C effect on triglyceride transport in tandem-perfused rat hind end and liver

1984 ◽  
Vol 247 (3) ◽  
pp. G305-G310
Author(s):  
W. J. Kortz ◽  
J. R. Nashold ◽  
M. R. Greenfield ◽  
H. Hilderman ◽  
S. H. Quarfordt
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Fatty Acyl ◽  
Liver Fat ◽  
Molar Ratio ◽  
Perfusion System ◽  
In Vitro Perfusion ◽  
Arterial Inflow ◽  
High Concentrations

The metabolism of double-labeled triglyceride in a synthetic emulsion was defined in an in vitro perfusion system of rat hind end and liver described previously [Am. J. Physiol. 245 (Gastrointest. Liver Physiol. 8): G106-G112, 1983]. The metabolism of [3H]glycerol-[14C]triolein was defined in the absence of added apoproteins and with additions of human CII and both CII and CIII. Without apoprotein, a pronounced lipolysis of the triglyceride was recognized by high concentrations of radiolabeled glycerol and free fatty acid in the perfusate. The removal of an aliquot of hind-end venous effluent 5 min after adding the labeled triglyceride emulsion to the arterial inflow demonstrated a brisk lipolysis of the substrate when incubated outside the perfusion system. The addition of CII protein to the emulsion before its introduction into the tandem system eliminated perfusate lipolysis, both within the perfusion system and in incubations of aliquots withdrawn from the system. Intravascular lipolysis was not seen with triglyceride emulsions containing both CII and CIH or when an aliquot of hind-end venous effluent was incubated with triglycerides that had not been exposed to the perfusion system. The intravascular lipolysis observed for the [14C]triglyceride added to the tandem system without apoproteins was associated with relatively greater recoveries of 14C-fatty acyl in liver, fat, and muscle and relatively greater recoveries of 14CO2 than when CII alone or both CII and CIII were added with the triglyceride. The addition of CIII to CII in a 1:1 molar ratio increased the recovery of 14C-fatty acyl in muscle and the recovery as 14CO2.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals NUTRITIONAL FACTORS IN FATTY ACID SYNTHESIS BY TISSUE SLICES IN VITRO

1952 ◽  
Vol 197 (1) ◽  
pp. 181-191 ◽  
Author(s):  
Grace. Medes ◽  
Alice. Thomas ◽  
Sidney. Weinhouse
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Acid Synthesis ◽  
Tissue Slices ◽  
Nutritional Factors
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