Fatty acid synthesis from amino acids in sheep adipose tissue

The rates of incorporation of 14C from 14C labelled acetate, glucose, alanine, leucine, isoleucine and valine into fatty acids has been measured in perirenal adipose tissue from foetal lambs and 8-month-old sheep, and into both fatty acids and acylglycerol glycerol in adipose tissue from 3-year-old sheep and 220-240 g female rats. Rates of incorporation of 14C from amino acids into fatty acids were much lower in adipose tissue from sheep (at all three ages) than from rats, whereas rates of incorporation of 14C into acylglycerol glycerol were either greater in sheep adipose tissue or the same as in rat adipose tissue. The rate of incorporation of 14C from amino acids into fatty acids decreased in the order leucine greater than alanine greater than isoleucine greater than valine in adipose tissue from rats and foetal lambs, and in the order leucine greater than alanine = isoleucine greater than valine in adipose tissue from 8-month- and 3-year-old sheep. Amino acids make a very small contribution to fatty acid synthesis in adipose tissue from sheep at all stages of development examined while fatty acids are a minor product of amino acid metabolism in sheep adipose tissue. The study provides further evidence for an important role for ATP-citrate lyase in restricting the utilization of acetyl-CoA generated in the mitochondria for fatty acid synthesis.     

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.     

Adipose tissue metabolism in sheep: response to season and its modulation by reproductive state

Seasonal changes in subcutaneous adipose tissue metabolism and serum metabolite and hormone concentrations are described in virgin ewes fed a fixed amount of a cereal mixture plus hay ad libitum. Body weight, adipocyte mean cell volume, the rates of fatty acid and acylglycerol glycerol synthesis, and lipoprotein lipase activity increased from October to May and then decreased over the following five months. These changes are probably due to an increase in voluntary food intake leading to increased availability of acetate for fatty acid synthesis and also a probable rise in serum insulin concentration. Seasonal changes in adipose tissue metabolism in sheep are modulated by pregnancy and lactation, possibly mediated in part by changes in the serum insulin: growth hormone ratio. Although seasonal changes in adipose tissue metabolism are paralleled by changes in serum prolactin concentration, prolactin probably does not have a direct effect on adipose tissue metabolism.     

Regeneration of renal proximal tubules after mercuric chloride injury is accompanied by increased binding of aminoacyl-transfer ribonucleic acid.

The liver of the foetal guinea pig accumulates a large quantity of triacyglycerol late in gestation at the same time that adipose-tissue mass grows at its maximum rate and foetal adipose-tissue lipoprotein lipase activity and sensitivity to lipolytic hormones has substantially declined. The fatty acid for triacyglycerol synthesis is not synthesized in the foetal liver and it is unlikely that it originates from any of the foetal tissues. Before the accumulation of hepatic triacyglycerol the concentration of free fatty acids increases in both the umbilical vein and the maternal inferior vena cava. This occurs at a time when the triacyglycerol lipase activity in maternal adipose tissue is elevated and the rate of lipolysis, but not of fatty acid esterification, is higher than earlier in gestation or than in the non-pregnant state. It is proposed that the increase in lipolysis in maternal adipose tissue, brought about by an increase in circulating lipolytic hormones, mobilizes fatty acid, which passes to the foetus and is partly stored as hepatic triacylglycerol. The foetal liver effectively removes both long-and short-chain fatty acids from umbilical-vein blood. The rate of placental fatty acid transfer is more than adequate to account for the triacylglycerol accumulation.     

Effect of rearing method on the storage of fats by adipose tissue in sheep

Adipocyte synthesis de novo and lipoprotein lipase activity have been used simultaneously to measure the lipogenic activity of adipose tissue in sheep. Acetate and glucose were used as precursors of fatty acid synthesis. The sheep were raised either outdoors or in a sheepfold. They were slaughtered by lots at mean weights of 24 and 32.5 kg. Compared to lipoprotein lipase activity, de novo synthesis of fatty acids was the main way of constituting lipid depositions. Raising the sheep outdoors favored the use of glucose as precursor of lipid synthesis at the first slaughter stage at 24 kg. Later at 32.5 kg, glucose utilization was practically zero compared to acetate, whatever the mode of rearing. The NADPH production needed for fatty acid synthesis was almost entirely due to NADP isocitrate dehydrogenase activity. Variations in both de novo synthesis and in lipoprotein lipase activity in relation with rearing method and slaughter weight were especially evident in the group raised outdoors.     

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

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 CO(2) 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 [(14)C]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.     

Utilization of methylmalonate for the synthesis of branched-chain fatty acids by preparations of chicken liver and sheep adipose tissue.

1. The utilization of methyl[2-14C]malonyl-CoA for fatty acid synthesis was investigated using synthetase preparations from chicken liver and sheep adipose tissue. 2. The rate of fatty acid synthesis from acetyl-CoA and malonyl-CoA was greatly diminished in the presence of methylmalonyl-CoA. 3. In the absence of malonyl-CoA, methylmalonyl-CoA was utilized for fatty acid synthesis only very slowly by the synthetase from sheep adipose tissue and not at all by that from chicken liver. 4. Despite the inhibitory effect of methylmalonyl-CoA on fatty acid synthesis from malonyl-CoA, it was utilized by the synthetase preparations from both species to produce a complex mixture of methyl-branched fatty acids.     

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 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.     

Influence of age and exercise training on lipid metabolism in Fischer-344 rats

The influence of training on fatty acid and glyceride synthesis by liver and adipose tissue homogenates of young and old Fischer-344 rats was examined. Four groups of rats (10 animals/group) were studied: young untrained, young trained, old untrained, and old trained. Training of each group was for 10 wk at 75% maximal O2 uptake. Young rats were killed at 6 mo of age and old rats were killed at 27 mo of age. Fatty acid synthesis was assessed by measuring the activities of acetyl-CoA carboxylase, fatty acid synthase, ATP citrate-lyase, "malic" enzyme, and glucose-6-phosphate dehydrogenase. Glyceride synthesis was evaluated by determining the rate of incorporation of [14C]glycerol 3-phosphate into lipids. In addition, lipoprotein lipase activity was measured in acetone-ether powders of adipose tissue from the four groups of rats. In liver, training had no effect on fatty acid or glyceride synthesis in either group. However, aging caused a significant decrease in the activities of four of the lipogenic enzymes but had no effect on glyceride synthesis. Training caused an increase in fatty acid synthase and glyceride synthesis in adipose tissue, and aging decreased lipoprotein lipase activity. It was concluded that training enhances the synthetic capacity of lipids by adipose tissue but that aging had a more profound effect in that the activities of the enzymes involved in these processes were lower in the old rats. Furthermore, the decreased activity of lipoprotein lipase in the older rats may explain the higher plasma triglyceride levels that were observed in these animals.     

Lipid biosynthesis in liver slices of the foetal guinea pig.

Lipid synthesis as measured by the incorporation of acetate or 3H2O into slices of foetal liver, is much higher than in slices of adult liver and shows a peak at about two-thirds of gestation. At this time the synthesis from glucose was low and reached a peak 10 days later. The changes in the activity of ATP citrate lyase, which mirrored acetate incorporation, and the effect of glucose and pyruvate on acetate corporation into lipid suggests that some of the lipid synthesis occurs via intramitochondrial acetyl-CoA production from acetate. Despite this, lipid synthesis was not inhibited by (-)-hydroxycitrate. The low rate of synthesis from glucose at two-thirds of gestation is ascribed to the low activity of pyruvate carboxylase at this time and a role for a phosphoenolpyruvate carboxykinase in providing oxaloacetate for lipogenesis is proposed. The activity of fatty acid synthetase broadly agreed with the changes in lipid synthesis, whereas the activity of acetyl-CoA carboxylase was barely sufficient to account for the rates of lipid synthesis in vivo. Acetate and short-chain fatty acids are likely to be the major precursors for lipid synthesis in vivo.     

Prenatal developmental changes in glucose transporters, intermediary metabolism and hormonal receptors related to the IGF/insulin-glucose axis in the heart and adipose tissue of bovines

Glucose transporter ontogenesis is likely to play a key role in glucose uptake by foetal tissues in order to satisfy their energy requirements. We thus investigated developmental changes in the bovine heart and perirenal adipose tissue in two glucose transporter isoforms, namely GLUT1 and GLUT4, the latter being responsible for the regulation of glucose uptake by insulin. Other key players of the glucose/insulin axis were also assessed. Plasma glucose concentration in the foetus was lower at 8 and 8.5 months of age than previously. In the heart, GLUT1 protein level markedly decreased between 3 and 4 months of age, whereas the number of insulin and IGF-I binding sites continually decreased, especially between 7 and 8 or 8.5 months of age. On the contrary, the GLUT4 level increased until 8 months of age and remained high until 2 weeks after birth. The activities of enzymes of glucose metabolism (namely phosphofructokinase [PFK] and lactate dehydrogenase [LDH]) increased throughout gestation and reached a plateau at 6 and 8.5 months of age for PFK and LDH, respectively. The activities of enzymes involved in fatty acid metabolism increased especially at birth. In perirenal adipose tissue, high mitochondrial activity was detected before birth which is a characteristic of brown adipose tissue. Furthermore, lipoprotein lipase activity and GLUT4 protein level markedly increased to reach a maximum at 6-7 and 8 months of age, and sharply decreased thereafter, whereas GLUT1 protein level increased between 6 and 7 months of age. In conclusion, considerable changes in the regulation of the insulin/glucose axis were observed from 6 months onwards of foetal development in both the heart and adipose tissue of cattle, which probably alters the potential of these tissues to use glucose or fat as energy sources.     

Adipose tissue metabolism during early pregnancy in the rat: temporal relationships of changes in the metabolic activity, number of insulin receptors, and serum hormone concentrations

The temporal relationships between changes in rates of fatty acid and acylglycerol glycerol synthesis; the activity of lipoprotein lipase of parametrial adipocytes and their capacity to bind insulin; and the serum concentrations of insulin, progesterone, prolactin, and total lactogenic activity have been examined in rats during the first 15 days of pregnancy. The rate of fatty acid and acylglycerol synthesis showed a transient increase at Days 9 and 12 of pregnancy, whereas there was no change in the activity of lipoprotein lipase activity except for a fall between Days 12 and 15 of pregnancy. The capacity of adipocytes to bind insulin was increased by Day 6 of pregnancy and remained elevated until at least Day 15; no changes in the affinity for insulin were observed. Serum progesterone, insulin, and total lactogenic activity were elevated by Days 3, 9, and 12 of pregnancy, respectively. The results show that progesterone but not placental lactogen could be responsible for the rise in the insulin-binding capacity of rat adipocytes during pregnancy, whereas the fall in lipogenic capacity at about Day 12 of pregnancy coincides with the rise in serum placental lactogen.     

Antilipogenic but not lipolytic effects of recombinant DNA-derived bovine somatotropin treatment on ovine adipose tissue; variation with genetic type

1. Lambs from three breeds (East Friesland, Oxford and Texel) were treated with recombinant DNA-derived bovine somatotropin (BST) at 0.05, 0.10, 0.20 mg/kg per day and fat metabolism assessed in subcutaneous adipose tissue biopsy samples. 2. BST treatment decreased adipose cell volume, fatty acid synthesis and acylglycerol glycerol synthesis but did not alter lipolytic rates (basal or noradrenaline-stimulated). 3. Genetic type influenced metabolism in a number of ways, most notably East Friesland lambs had lower fatty acid esterification rates and responded poorly to BST in terms of reduced lipogenesis as compared to the Oxford and Texel lambs. 4. Blood urea concentration was decreased by BST treatment suggesting increased nitrogen retention. 5. These results emphasise the role of somatotropin as an inhibitor of adipose tissue lipogenesis but cast further doubt on a physiological role in regulating lipolysis.     

In vitro lipid metabolism in the rat pancreas. I. Basal lipid metabolism.

1. The in vitro basal lipid metabolism of rat pancreatic fragments was compared with that in adipose tissue fragments and liver slices. 2. [1-14C]Acetate added to the media was mostly incorporated into palmitic acid and to a lesser extent into oleic acid. In addition, pancreatic tissue exhibited a marked capacity for elongation of polyunsaturated fatty acids by [1-14C]acetate and resulting desaturation when compared to adipose tissue and liver. 3. Data obtained in the presence of [U-14C]glucose, [1-14C]palmitate and 3H20 indicate that acetyl-CoA derived from glucose and from beta-oxidation of fatty acids contributed to de novo lipogenesis. 4. Oxidation of [1-14C]palmitic acid was 9-13 times higher in the pancreas than in adipose tissue or liver when expressed on a wet weight basis. 5. The fatty acid moiety of pancreatic glycerolipids could be derived from de novo synthesis, fatty acids added to the medium, or from fatty acids formed from the hydrolysis of endogenous lipids. The glycerol moiety could be derived either from glucose, or directly from glycerol through participation of glycerol kinase.     

The relative significance of acetate and glucose as precursors for lipid synthesis in liver and adipose tissue from ruminants

1. The incorporation of labelled glucose into lipid by liver slices from sheep and cows is considerably less than that by liver slices from the rat, although oxidation to carbon dioxide occurs to a similar extent. ATP citrate lyase and NADP malate dehydrogenase are inactive in both sheep and cow liver but active in rat liver. The absence of the citrate-cleavage pathway of lipogenesis in ruminant liver has been confirmed by the negligible amounts of C-3 of aspartate incorporated into fatty acids. 2. Considerable amounts of [(14)C]acetate are incorporated into fatty acids and non-saponifiable lipid in rat and ruminant liver. Acetyl-CoA synthetase, the initial enzyme in the metabolism of acetate, has a high activity in liver from rat and ruminants. 3. In adipose tissue from ruminants more acetate than glucose is converted into lipids, whereas the converse is true in rat adipose tissue. The greater incorporation of [(14)C]acetate into fatty acids in adipose tissue from the ruminant as compared with the non-ruminant may be caused, in part, by the higher activity of acetyl-CoA synthetase activity in the ruminant. 4. The results suggest that, in both liver and adipose tissue from ruminants, acetate is a more important source of lipid than glucose. 5. Two enzymes of the hexose monophosphate shunt, glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase, are active in both tissues and from the three species.     

Fatty acid biosynthesis in liver and adipose tissue from dogs

Production of CO2, fatty acids and glycerol from glucose and acetate was measured in slices of liver and adipose tissue taken from mature dogs. Acetate was the predominant carbon source for de novo fatty acid synthesis in both tissues. Fatty acid synthesis occurred at greater rates in adipose tissue than in liver. Glucose provided carbon for glycerol synthesis production in adipose tissue. Results support the concept that adipose tissue, and not liver, is the principal anatomical site for fatty acid synthesis in dogs.     

Metabolic adaptations during lactogenesis. Fatty acid synthesis in rabbit mammary tissue during pregnancy and lactation

1. Mammary tissue was obtained from rabbits at various stages of pregnancy and lactation and used for tissue-slice incubations (to measure the rate of fatty acid synthesis and CO(2) production) and to determine relevant enzymic activities. A biphasic adaptation in fatty acid synthetic capacity during lactogenesis was noted. 2. The first lactogenic response occurred between day 15 and 24 of pregnancy. Over this period fatty acid synthesis (from acetate) increased 14-fold and the proportions of fatty acids synthesized changed to those characteristic of milk fat (77-86% as C(8:0)+C(10:0) acids). 3. The second lactogenic response occurred post partum as indicated by increased rates of fatty acid synthesis and CO(2) production (from acetate and glucose) and increased enzymic activities. 4. Major increases in enzymic activities between mid-pregnancy and lactation were noted for ATP citrate lyase (EC 4.1.3.8), acetyl-CoA synthetase (EC 6.2.1.1), acetyl-CoA carboxylase (EC 6.4.1.2), fatty acid synthetase, glucose 6-phosphate dehydrogenase (EC 1.1.1.49), and 6-phosphogluconate dehydrogenase (EC 1.1.1.44). Smaller increases in activity occurred with glycerol 3-phosphate dehydrogenase (EC 1.1.1.8) and NADP(+)-isocitrate dehydrogenase (EC 1.1.1.42) and the activity of NADP(+)-malate dehydrogenase (EC 1.1.1.40) was negligible at all periods tested. 5. During pregnancy and lactation there was a close temporal relationship between fatty acid synthetic capacity and the activities of ATP citrate lyase (r=0.94) and acetyl-CoA carboxylase (r=0.90).     

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

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-(14)C]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.     

Lipogenesis in liver and adipose tissue of the domestic cat (Felis domestica)

1. Production of fatty acids, CO2 and glycerol from glucose and acetate was determined in slices of liver and adipose tissue taken from mature cats. 2. Acetate was the predominant carbon source for de novo fatty acid synthesis in both liver and adipose tissue. 3. Fatty acid synthesis occurred at much greater rates in adipose tissue than in liver. 4. Relative lipogenic capacity (ratio of production of long-chain fatty acids and glycerol to oxidation of substrates) was 20 times greater in adipose tissue than in liver with both substrates.     

Caloric restriction leads to regional specialisation of adipocyte function in the rat

The study analysed the responses of three metabolic parameters in five distinct adipose tissue depots to caloric restriction (4 weeks) in the rat. The aims were to evaluate whether specific adipose tissue depots were recruited for triacylglycerol (TAG) storage and/or mobilisation, and to determine to what extent specific adipose tissue depots exhibited preferences for the source of fatty acid (FA) for TAG storage. Caloric restriction led to a general enhancement of the response of lipoprotein lipase (LPL), FA synthesis and glucose utilisation to a meal. Effects were particularly marked in the parametrial, perirenal and interscapular depots compared with mesenteric and subcutaneous depots. There was no evidence that individual depots selectively expressed a preference for the pathways concerned with the generation of FA for storage (the exogenous (LPL) and the endogenous (synthesis) pathway). However, the temporal sequence of activation of these pathways differed in a manner consistent with a switch from preponderant use of FA produced via de novo synthesis during the very early phase of feeding towards later use of FA derived from circulating TAG. The overall excursions in insulin levels observed in the calorie-restricted rats were comparable to those found in free-feeding rats, but the magnitude and the rapidity of the individual metabolic responses of the adipocyte were augmented. The data are consistent with a general enhancement of insulin sensitivity and responsiveness in adipose tissue of calorie-restricted rats, together with adaptive regional specialisation of adipocyte function. These adaptations would be predicted to facilitate the immediate conservation of dietary nutrients by promoting their storage as the FA or glycerol moieties of adipose tissue TAG and thereby to ensure the regulated release of FA and glycerol from adipose tissue in accordance with the requirement for glucose conservation and/or production.