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.

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.

Fatty Acid Synthesis from Pyruvate in White Adipose Tissue: the Effect of Norepinephrine

1971 ◽  
Vol 49 (6) ◽  
pp. 736-741 ◽  
Author(s):  
M. L. Halperin
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Acid Synthesis ◽  
Pentose Phosphate ◽  
Epididymal Adipose Tissue ◽  
Phenazine Methosulfate ◽  
Fasted Rats ◽  
Lines Of Evidence

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).

The 1990 Borden Award Lecture Dietary regulation of fatty acid and triglyceride metabolism

1991 ◽  
Vol 69 (11) ◽  
pp. 1637-1647 ◽  
Author(s):  
Gene R. Herzberg
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Lipoprotein Lipase ◽  
Fatty Acid Synthesis ◽  
Dietary Fat ◽  
Acid Synthesis ◽  
Fish Oils ◽  
Dietary Fish

The level of circulating triacylglycerols is determined by the balance between their delivery into the plasma and their removal from it. Plasma triacylglycerols are derived either from dietary fat as chylomicrons or from endogenous hepatic synthesis as very low density lipoproteins. Their removal occurs through the action of lipoprotein lipase after which the fatty acids are either stored in adipose tissue or oxidized, primarily in skeletal muscle and heart. The composition of the diet has been shown to influence many of these processes. Hepatic fatty acid synthesis and triacylglycerol secretion are affected by the quantity and composition of dietary fat, carbohydrate, and protein. Polyunsaturated but not saturated fats reduce hepatic fatty acid synthesis by decreasing the amount of the lipogenic enzymes needed for de novo fatty acid synthesis. Dietary fish oils are particularly effective at reducing both fatty acid synthesis and triacylglycerol secretion and as a result are hypotriacylglycerolemic, particularly in hypertriacylglycerolemic individuals. In addition, dietary fish oils can increase the oxidation of fatty acids and lead to increased activity of lipoprotein lipase in skeletal muscle and heart. It appears that the hypotriacylglycerolemic effect of dietary fish oils is mediated by effects on both synthesis and removal of circulating triacylglycerols.Key words: lipid, fish oil, fructose, liver, adipose tissue, oxidation.

Effects of pregnancy and ovarian steroids on fatty acid synthesis and uptake in Syrian hamsters

1991 ◽  
Vol 260 (1) ◽  
pp. R153-R158 ◽  
Author(s):  
A. J. Bhatia ◽  
G. N. Wade
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
White Adipose Tissue ◽  
Fatty Acid Synthesis ◽  
De Novo ◽  
Acid Synthesis ◽  
De Novo Lipogenesis ◽  
Ovarian Steroids ◽  
Syrian Hamsters

The effects of pregnancy and ovarian steroids on the in vivo distribution of newly synthesized fatty acids (incorporation of tritium from 3H2O into fatty acid) in Syrian hamsters (Mesocricetus auratus) were examined. During late, but not early, gestation hamsters had reduced levels of newly synthesized fatty acids in heart, liver, uterus, and white adipose tissues (parametrial and inguinal fat pads). Treatment of ovariectomized hamsters with estradiol + progesterone significantly decreased fatty acid synthesis-uptake in heart, liver, and inguinal white adipose tissue. Treatment with either estradiol or progesterone alone was without significant effect in any tissue. Pretreatment of hamsters with Triton WR-1339 (tyloxapol), an inhibitor of lipoprotein lipase activity and tissue triglyceride uptake, abolished the effects of estradiol + progesterone in white adipose tissue and heart but not in liver. Thus hamsters lose body fat during pregnancy in part because of decreased de novo lipogenesis. The effect of pregnancy on lipogenesis is mimicked by treatment with estradiol + progesterone but not by either hormone alone. Furthermore, it appears that the liver is the principal site of estradiol + progesterone action on lipogenesis in Syrian hamsters.

scholarly journals Studies on the role of insulin in the regulation of glyceride synthesis in rat epididymal adipose tissue

1975 ◽  
Vol 150 (3) ◽  
pp. 441-451 ◽  
Author(s):  
S R Sooranna ◽  
E D Saggerson
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Acid Synthesis ◽  
Synthesis Process ◽  
Epididymal Adipose Tissue ◽  
Fat Cells ◽  
Fat Cell ◽  
Glyceride Synthesis

1. When rat isolated fat-cells were incubated with fructose and palmitate, insulin significantly stimulated glyceride synthesis as measured by either [14C]fructose incorporation into the glycerol moiety or of [3H]palmitate incorporation into the acyl moiety of tissue glycerides. Under certain conditions the effect of insulin on glyceride synthesis was greater than the effect of insulin on fructose uptake. 2. In the presence of palmitate, insulin slightly stimulated (a) [14C]pyruvate incorporation into glyceride glycerol of fat-cells and (b) 3H2O incorporation into glyceride glycerol of incubated fat-pads. 3. At low extracellular total concentrations of fatty acids (in the presence of albumin), insulin stimulated [14C]fructose, [14C]pyruvate and 3H2O incorporation into fat-cell fatty acids. Increasing the extracellular fatty acid concentration greatly inhibited fatty acid synthesis from these precursors and also greatly decreased the extent of apparent stimulation of fatty acid synthesis by insulin. 4. These results are discussed in relation to the suggestion [A.P. Halestrap & R.M Denton (1974) Biochem. J. 142, 365-377] that the tissue may contain a specific acyl-binding protein which is subject to regulation. It is suggested that an insulin-sensitive enzyme component of the glyceride-synthesis process may play such a role.

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

1978 ◽  
Vol 176 (3) ◽  
pp. 799-804 ◽  
Author(s):  
J R Scaife ◽  
K W J Wahle ◽  
G A Garton
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Complex Mixture ◽  
Acid Synthesis ◽  
Inhibitory Effect ◽  
Chicken Liver ◽  
Malonyl Coa ◽  
Branched Chain

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.

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.

scholarly journals Fatty acid synthesis in liver and adipose tissue of normal and genetically obese (ob/ob) mice during the 24-hour cycle

1975 ◽  
Vol 150 (2) ◽  
pp. 167-173 ◽  
Author(s):  
D A Hems ◽  
E A Rath ◽  
T R Verrinder
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Dark Period ◽  
Acid Synthesis ◽  
Obese Mice ◽  
Total Rate ◽  
Relative Significance ◽  
Adipose Organ

1. The synthesis of long-chain fatty acids de novo was measured in the liver and in regions of adipose tissue in intact normal and genetically obses mice throughout the daily 24h cycle. 2. The total rate of synthesis, as measured by the rate of incorporation of 3H from 3H2O into fatty acid, was highest during the dark period, in liver and adipose tissue of lean or obese mice. 3. The rate of incorporation of 14C from [U-14C]glucose into fatty acid was also followed (in the same mice). The 14C/3H ratios were higher by a factor of 5-20 in parametrial and scapular fat than that in liver. This difference was less marked during the dark period (of maximum fatty acid synthesis). 4. In normal mice, the total rate of fatty acid synthesis in the liver was about twofold greater than that in all adipose tissue regions combined. 5. In obese mice, the rate of fatty acid synthesis was more rapid than in lean mice, in both liver and adipose tissue. Most of the extra lipogenesis occurred in adipose tissue. The extra hepatic fatty acids synthesized in obese mice were located in triglyceride rather than phospholipid. 6. In adipose tissue of normal mice, the rate of fatty acid synthesis was most rapid in the intra-abdominal areas and in brown fat. In obese mice, all regions exhibited rapid rates of fatty acid synthesis. 7. These results shed light on the relative significance of liver and adipose tissue (i.e. the adipose ‘organ’) in fatty acid synthesis in mice, on the mino importance of glucose in hepatic lipogenesis, and on the alterations in the rate of fatty acid synthesis in genetically obese mice.

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