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Biomedical subjects

R G Vernon

Publications and source records attributed to R G Vernon.

At least 127 records · Page 7Linked to original sources

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

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 CO(2); 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.

Adenine Nucleotides↗

Lipolysis in rat adipocytes during pregnancy and lactation. The response to noradrenaline.

1. Lipolysis has been measured in parametrial adipocytes from virgin, pregnant and lactating rats. 2. The basal rate and the maximal rate of lipolysis, the latter measured in the presence of noradrenaline and theophylline, remained constant between the three experimental categories, with the exception of a significant transient increase in the basal rate at parturition. 3. The noradrenaline-stimulated lipolysis rate rose above the virgin rate during pregnancy and fell below it during lactation; inclusion of adenosine deaminase in incubations abolished these differences in response to noradrenaline. 4. Cyclic AMP phosphodiesterase activity was lower in adipocytes during pregnancy and lactation than in virgin animals.

3',5'-Cyclic-AMP Phosphodiesterases↗

Enzyme and protein turnover in adipose tissue in pregnancy and lactation.

1. The relative rates of synthesis of fatty acid synthetase and the pyruvate dehydrogenase complex were measured in adipose tissue in virgin, late pregnant and early lactating rats after injection of L-[2,3-3H]alanine. The relative rate of synthesis of fatty acid synthetase decreased approximately 4-fold between 2 days prepartum and 2 days postpartum. The relative rate of synthesis of the pyruvate dehydrogenase complex did not change. 2. The fractional rate of total adipose tissue protein synthesis was measured by constant infusion with L-[U-14C]tyrosine. Total protein synthesis did not differ in virgin and 2-day lactating rats. The half-life of adipose tissue protein in virgin rats determined by decay of 14C label from protein after injection of NaH14CO3 was 86.9 +/- 6.7 h. This is in close agreement with the half-life (82.5 +/- 20 h) calculated from the fractional rate of protein synthesis determined by the constant infusion method.

Adipose Tissue↗

Fatty acid and acylglycerol glycerol synthesis in isolated liver cells from foetal lambs.

1. The rates of fatty acid and acylglycerol glycerol synthesis from acetate, glucose and L-lactate in isolated liver cells from foetal lambs at about 30 and 3 days before birth are reported. The total rates of fatty acid synthesis from endogenous precursors and added substrates, measured using 3H2O, are also reported for these liver cells. 2. The total rate of fatty acid synthesis did not differ at the two ages. Of the added substrates, acetate and L-lactate were better precursors for fatty acid synthesis than glucose under the conditions used. Endogenous precursors, probably glycogen glucose, made a substantial contribution to fatty acid synthesis. 3. Results are compared with previous studies of fatty acid synthesis in adipose tissue from foetal lambs.

Acetates↗

Plasma unesterified fatty acid and triacylglycerol concentration of the goat (Capra hircus) during pregnancy and lactation.

1. The concentrations of unesterified fatty acids and triacylglycerol were measured in plasma obtained from goats at various stages of pregnancy and lactation. 2. The plasma unesterified fatty acid concentration increased during the last third of pregnancy: highest concentrations were found at parturition and during early lactation. 3. The plasma triacylglycerol concentration showed a transient increase during mid-pregnancy: the concentration fell around parturition and no evidence for hypertriglyceridemia was found during late-pregnancy. 4. Results are compared with those of other studies of ruminant and non-ruminant species.

Animals↗

Development in vitro of fatty acid synthesis in perirenal adipose tissue from new-born lambs.

Pieces of perirenal adipose tissue from new-born lambs were maintained in tissue culture for 5 days in the presence of insulin. During this period there was a 7-fold increase in the rate of fatty acid synthesis. Both omission of insulin from the culture medium and addition of ovine growth hormone to the culture medium resulted in a significantly lower rate of fatty acid synthesis. The results are compared with changes in the rate of fatty acid synthesis in vivo in neonatal lambs and the probable roles of insulin and growth hormone in the regulation of fatty acid synthesis in neonatal lambs are discussed.

Adipose Tissue↗

Metabolism of sheep adipose tissue during pregnancy and lactation. Adaptation and regulation.

1. Changes in the mean volume, the rate of fatty acid and acylglycerol glycerol synthesis, the activity of lipoprotein lipase and the numbers and affinities of insulin receptors of subcutaneous adipocytes are reported for sheep at different stages of pregnancy and lactation. In addition, the serum concentrations of insulin, progesterone, prolactin, choriomammotropin, somatotropin, glucose, acetate, L-lactate, glycerol and unesterified fatty acids are reported for these sheep. 2. A switch from lipid accumulation to net lipid mobilization accompanied by a decline in the capacity for lipid synthesis, occurred at the onset of the last third of pregnancy. Net lipid mobilization continued during lactation. 3. The changes that occurred in the serum concentrations of the various hormones listed above are discussed in relation to their possible roles in the modulation of adipose tissue metabolism in sheep during pregnancy and lactation. The observations are compared with those from previous studies on the hormonal control of adipose tissue metabolism in the rat during pregnancy and lactation.

Adaptation, Physiological↗

L-Lactate as a source of carbon for fatty acid synthesis in adult and foetal sheep.

The contribution of carbon from acetate, glucose and L-lactate to fatty acid synthesis has been compared in adipose tissue from adult and foetal sheep. Adipose tissue slices were incubated with mixtures of acetate, glucose and L-lactate at concentrations found in sheep blood. Under these conditions acetate, glucose and L-lactate contributed 95, 2 and 3%, respectively, of the C2 units used for fatty acid synthesis in adipose tissue slices from adult sheep. In contrast, acetate, glucose and L-acetate provided 50, 17 and 33%, respectively, of the C2 units for fatty acid synthesis in adipose tissue slices from foetal lambs (about 30 days prior to birth). The contribution of acetate and L-lactate carbon to fatty acid synthesis varied with their concentrations over the normal physiological range at both ages. We conclude that L-lactate is normally a minor source of carbon for fatty acid synthesis in the adult sheep but is an important source in foetal lambs.

Acetates↗

Aspects of adipose-tissue metabolism in foetal lambs.

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'.

Adipose Tissue↗

Prolactin and the regulation of adipose-tissue metabolism during lactation in rats.

Removal of litters from young lactating rats for 24 or 48 h or treatment of lactating rats with bromocriptine increased the rate of fatty acid synthesis and the activities of lipoprotein lipase and fatty acid synthetase in adipose tissue, decreased the lipoprotein lipase and fatty acid synthetase activities of mammary gland and lowered the serum-prolactin concentration. Concurrent injections of prolactin prevented the effects of bromocriptine and 24 h of litter removal on most of these changes in adipose tissue, but did not prevent the effects of 48 h of litter removal. The results suggest that effects of prolactin on adipose-tissue metabolism are dependent on a functional mammary gland. Most of the responses of adipose tissue to litter removal were reduced in older rats.

Adipose Tissue↗

Lipogenic enzymes in rat maternal adipose tissue in the perinatal period.

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.

Acetyl-CoA Carboxylase↗

Regulation of adipocyte insulin receptor number and metabolism during late-pregnancy.

The regulation of the rate of fatty acid synthesis of rat adipose tissue during late-pregnancy has been investigated. Rats at day 18 of pregnancy were injected over a 2-day period with either prostaglandin F2 alpha (PGF2 alpha), PGF2 alpha plus progesterone, PGF2 alpha plus bromocriptine or carrier solutions, and were then killed on day 20 of pregnancy. Injections of PGF2 alpha resulted in a decreased rate of fatty acid synthesis, a lower serum-insulin concentration, and a reduced number of insulin receptors of adipocytes. Concurrent injections of progesterone, but not of bromocriptine, along with the PGF2 alpha prevented these effects of the latter. The results are consistent with our previous suggestion that the fall in serum progesterone concentration prior to parturition results in a reduction in the number of insulin receptors of adipocytes, which, along with a fall in the serum-insulin concentration, leads to a decrease in the anabolic activity of the tissue.

Adipose Tissue↗