scholarly journals Regulation of glycolysis and fatty acid synthesis from glucose in sheep adipose tissue

1982 ◽  
Vol 206 (3) ◽  
pp. 577-586 ◽  
Author(s):  
James P. Robertson ◽  
Anne Faulkner ◽  
Richard G. Vernon

1. The following were measured in adipose-tissue pieces, obtained from 7–9 month-old sheep, before or after the tissue pieces had been maintained in tissue culture for 24 h: the rates of synthesis from glucose of fatty acids, acylglycerol glycerol, pyruvate and lactate; the rate of glucose oxidation to CO2; the rate of glucose oxidation via the pentose phosphate pathway; the activities of hexokinase, glucose 6-phosphate dehydrogenase, phosphofructokinase, pyruvate kinase, pyruvate dehydrogenase and ATP citrate lyase; the intra- and extra-cellular water content; the concentration of various metabolites and ATP, ADP and AMP. 2. The proportion of glucose carbon converted into the various products in sheep adipose tissue differs markedly from that observed in rat adipose tissue. 3. There was a general increase in the rate of glucose utilization by the adipose-tissue pieces after maintenance in tissue culture; largest changes were seen in the rates of glycolysis and fatty acid synthesis from glucose. These increases are paralleled by an increase in pyruvate kinase activity. There was no change in the activities of the other enzymes as measured, although the net flux through all the enzymes increased. 4. Incubation of fresh adipose-tissue pieces for 2–6h led to an increase in the affinity of pyruvate kinase for phosphoenolpyruvate. 5. The rate of pyruvate production by glycolysis was greater than the activity of pyruvate dehydrogenase of the tissue. 6. The results suggest that both pyruvate kinase and pyruvate dehydrogenase have important roles in restricting the utilization of glucose carbon for fatty acid synthesis in sheep adipose tissue.

1980 ◽  
Vol 186 (3) ◽  
pp. 937-944 ◽  
Author(s):  
P A Sinnett-Smith ◽  
R G Vernon ◽  
R J Mayer

1. The specific activities of fatty acid synthetase, acetyl-CoA carboxylase and pyruvate dehydrogenase were measured in rat adipose-tissue extracts in pregnancy and lactation. Fatty acid synthetase specific activity correlates very closely with the rate of fatty acid synthesis, the enzyme specific activity decreasing after mid-pregnancy in a manner very similar to the rate of fatty acid synthesis. Acetyl-CoA carboxylase specific activity also decreases dramatically after mid-pregnancy. Initial pyruvate dehydrogenase specific activity shows a decrease between 2 days pre partum and 2 days post partum, but total enzyme activity shows no significant change in the same period. 2. Immunotitrations of fatty acid synthetase and pyruvate dehydrogenase activities were carried out; the titrations showed that the change in the fatty acid synthetase activity is due to a change in the enzyme amount; the amount of pyruvate dyhydrogenase does not change. Therefore the decrease in fatty acid biosynthesis in subcutaneous and parametrial adipose tissue in late pregnancy and early lactation is associated with a decrease in the amount of at least one of the enzymes involved in fatty acid biosynthesis. The correlation of these events with known hormonal changes is discussed.


1988 ◽  
Vol 256 (3) ◽  
pp. 873-878 ◽  
Author(s):  
R G Vernon ◽  
E Finley

1. Lactation results in a substantial fall in the rate of fatty acid synthesis in sheep adipose tissue. 2. Maintenance of adipose tissue from non-lactating sheep in tissue culture for 24 or 48 h with insulin increased the rate of fatty acid synthesis. Dexamethasone, a glucocorticoid analogue, alone inhibited the rate of fatty acid synthesis, but enhanced the stimulatory effect of insulin. Growth hormone (somatotropin) antagonized the increase in the rate of fatty acid synthesis induced by insulin or insulin plus dexamethasone. 3. Maintenance of adipose tissue from lactating sheep in tissue culture resulted in a small increase in the rate of fatty acid synthesis after 24 h, and then a large increase in rate between 24 and 48 h of culture. The increase during the second 24 h period was dependent on the presence of insulin; this effect was enhanced by dexamethasone and inhibited by growth hormone. 4. The increase in the rate of fatty acid synthesis in tissue from non-lactating sheep and in tissue from lactating sheep during the major increase in rate was prevented by actinomycin D, an inhibitor of transcription. 5. Effects of insulin and growth hormone were observed with physiological concentrations of the hormones. 6. The study suggests that known changes in the serum concentrations of insulin and growth hormone are the primary causes of the changes in fatty acid synthesis in adipose tissue during the lactation cycle in sheep. 7. During lactation, adipose tissue becomes refractory to insulin in sheep; responsiveness is partly restored by tissue culture in the presence of insulin and dexamethasone.


1977 ◽  
Vol 166 (3) ◽  
pp. 627-630 ◽  
Author(s):  
J G McCormack ◽  
R M Denton

Plasma insulin concentrations in cold-adapted rats were altered acutely by administration of glucose or anti-insulin serum. Rates of fatty acid synthesis in interscapular brown adipose tissue were determined from the incorporation of 3H from 3H2O into tissue lipid. Rates of synthesis were greatly elevated after glucose administration and markedly decreased after injection with anti-insulin serum. Parallel changes in the initial activities of both acetyl-CoA carboxylase and pyruvate dehydrogenase were observed under these conditions, but no changes in total activities were evident. The results suggest that this tissue is an important site of fatty acid synthesis in the cold-adapted rat and that this feature of the tissue is sensitive to changes in plasma insulin concentrations.


1976 ◽  
Vol 160 (2) ◽  
pp. 413-416 ◽  
Author(s):  
D Stansbie ◽  
R W Brownsey ◽  
M Crettaz ◽  
R M Denton

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.


1971 ◽  
Vol 49 (6) ◽  
pp. 736-741 ◽  
Author(s):  
M. L. Halperin

Pyruvate incorporation into fatty acids has been studied in epididymal adipose tissue taken from normal and 24-h-fasted rats. This rate was limited by the rate of cytoplasmic NADPH2 generation as suggested by three lines of evidence.(1) D-Glucose-12C increased pyruvate-U-14C incorporation into fatty acids threefold. This augmentation was independent of L-glycerol 3-phosphate concentrations as the level of this metabolite was not increased. Addition of lactate-U-14C to the pyruvate medium increased the tissue L-glycerol 3-phosphate levels but did not increase the rate of fatty acid synthesis.(2) Phenazine methosulfate (2 μM) inhibited pyruvate or pyruvate plus lactate (L/P = 3/1) conversion to fatty acids whilst stimulating fatty acid synthesis from glucose or lactate alone.(3) Norepinephrine stimulated pyruvate but not glucose or glucose plus pyruvate incorporation into fatty acids. This correlated with norepinephrine-induced glycogenosis and NADPH2 production in the pentose phosphate pathway. This was shown by increased 1-14CO2/6-14CO2 production from endogenously labelled glycogen and the absence of this effect in glycogen-depleted adipocytes (24-h-fasted rats).


1975 ◽  
Vol 53 (10) ◽  
pp. 1054-1060 ◽  
Author(s):  
Wayne M. Taylor ◽  
Mitchell L. Halperin

In adipocytes from fed rats, the rate of fatty acid synthesis in the presence of glucose and insulin was inhibited 40% by valine (5 mm). This inhibition was largely abolished by the addition to the incubation medium of the transaminase inhibitor aminooxy acetate, and of pyruvate and agents which raise the intracellular pyruvate levels such as N,N,N1,N1-tetramethyl-p-phenylenediamine.Pyruvate output into the incubation medium from fat pads obtained from fed rats and incubated with glucose and insulin was decreased significantly by the addition of valine. When adipocytes were incubated under similar conditions, the final concentration of pyruvate in the incubation medium was 42 ± 1.6 μM under control conditions and approximately one third of this value in the presence of 2.5 mM valine.Valine had no significant effect on pyruvate dehydrogenase (lipoate) (EC 1.2.4.1) activity when assayed in homogenates prepared from adipose tissue previously incubated for 60 min with the amino acid. Although the ketoacid analogue of valine, α-ketoisovaleric acid, is a competitive inhibitor of pyruvate dehydrogenase (lipoate) (Ki = 1.4 mM), this cannot solely account for the valine-induced reduced rate of lipogenesis. Rather, the mechanism involves a reduction in pyruvate concentration and thereby a diminished flow through pyruvate dehydrogenase (lipoate). Details of the possible mechanism are discussed.


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