Rate Of Lipid Synthesis Research Articles

Regulation of lipid synthesis during early premolt in decapod crustaceans

1. 1. The in vitro incorporation of 1- 14C-sodium acetate into chloroform—methanol extractable lipid of the hepatopancreas was shown to be linear up to 75 min in Pachygrapsus crassipes (intertidal marine crab) and Procambarus astacus (fresh-water crayfish). 2. 2. The turnover rate of hepatopancreatic lipid labeled with 1- 14C-sodium acetate is similar in intermolt animals and those destalked for 48 hr. 3. 3. The turnover rate of hepatopancreatic lipid labeled with 1- 14C-palmitic acid is lower in 48-hr destalked crayfish than in normal intermolt animals. 4. 4. Removal of the Y-organ does not alter the increase in hepatopancreatic lipid synthesis observed in destalked P. crassipes. 5. 5. Injections of ecdysterone into intermolt P. astacus does not result in an increase in the rate of lipid synthesis in the hepatopancreas.

Endocrine Regulation of Lipid Synthesis in Decapod Crustaceans

The legulation of lipid synthesis in the hepatopancreas of the crab Pachygrapsus crassipes and the crayfish Procambarus sp. was investigated. Although deatalking induces an increase in the rate of 14C-1-acetate incorporation into lipid, injections of crustecdysone into intermolt animals fail to elicit a similar response. In addition, the increased rate of lipid synthesis induced by destalking is unaffected by removal of the Y-organ. It would appear then that the increase in lipid synthesis characteristic of early premolt is not controlled by either crustecdysone or the Y-organ. It is suggested that formation of acetyl-CoA by any one of a number of possible mechanisms may bethe manner in which the increase in fatty acid synthesis is effected during premolt.

Inhibition of lipogenesis in rat liver by (−)-hydroxycitrate

The purpose of these investigations was to determine the effect of the stereoisomers of hydroxycitrate on the rate of lipogenesis in rat liver. These observations were made under conditions in which there was an induced rate of lipid synthesis. Only (−)-hydroxycitrate significantly decreased the conversion of [ 14C]citrate into lipid in liver high speed supernatant and the conversion of [ 14C]alanine into lipid in vivo. The in vivo rate of lipogenesis was markedly decreased for 150 min following the administration of (−)-hydroxycitrate either iv (0.017 mmoles/kg) or ip (0.0263 mmoles/kg). Fatty acid and cholesterol synthesis were significantly inhibited by the oral administration of (−)-hydroxycitrate (5.26, 3.95 and 2.63 mmoles/kg) only when the compound was given before the feeding period.

Effect of glycerol deprivation on the phospholipid metabolism of a glycerol auxotroph of Staphylococcus aureus.

A study of the effects of glycerol deprivation on the content and metabolism of the phospholipids of a glycerol auxotroph of Staphylococcus aureus showed that (i) there was an increase in the proportions of lysylphosphatidylglycerol (LPB) and a concomitant decrease in the proportion of phosphatidylglycerol. The total phospholipid content per sample and the proportion of cardiolipin did not change, but the phosphatidic acid increased transiently and then fell to pretreatment levels. (ii) The loss of (32)P from the lipids during the chase in a pulse-chase experiment was essentially the same in phosphatidylglycerol, cardiolipin, and phosphatidic acid during glycerol deprivation or growth in the presence of glycerol. LPG lost half the radioactivity in slightly more than two doubling times when grown with glycerol. In the absence of glycerol, (32)P accumulated in LPG for about 20 min and then stopped, after which time there was no apparent turnover. (iii) During glycerol deprivation, the initial (32)P incorporation decreased sixfold compared to that of the control with glycerol. The initial incorporation into LPG decreased only 2.5-fold, whereas that of PG decreased 45-fold. (iv) During glycerol deprivation, the free fatty acid content increased from 1.2 to 12.5% of the total extractable fatty acids and then slowly decreased. The increase was largely iso- and anti-iso-branched 21-carbon-atom fatty acids. In glycerol-supplemented cultures, the major fatty acids were branched 14- to 18-carbon fatty acids. The decrease in longer chain free fatty acids after 60 min represented their esterification into lipids. (v) During glycerol deprivation ribonucleic acid synthesis and cell growth continued for 40 min and protein synthesis continued for 90 min. Then synthesis and growth stopped. (vi) After the addition of glycerol to glycerol-deprived cells, (32)P and (14)C-glycerol were incorporated into the phospholipids without lag; ribonucleic acid, protein synthesis, and cell growth began after a 5- to 10-min lag at the pretreatment rate. The initial rate of lipid synthesis after the addition of glycerol was three times greater than the growth rate. This rapid rate continued for about 25 min until the lipid content and proportions of LPG and phosphatidylglycerol were restored.

Changes in lipid and protein synthesis during spermatozoan development and thoracic tissue maturation inDrosophila hydei.

The synthesis of protein and lipid was studied in the testis and thoracic tissues ofDrosophila hydei by radioisotope incorporation. The formation and accumulation of late stage gametes in the testes during maturation was accompanied by more than 4-fold increases in both lipid and protein synthesis rates. Though there was an 8-fold increase in the rate of protein synthesis during thoracic tissue maturation, the rate of lipid synthesis little more than doubled. By comparison the rates of protein synthesis were high in mature testis and thoracic tissues, whereas the rate of lipid synthesis was high in the mature testis but low in both immature and mature thoracic tissues.Label incorporation from pyruvate and L-alanine into protein in thoracic tissue appeared to be highly dependent on Krebs cycle activity, whereas pyruvate and L-alanine label incorporation into protein in the testis was primarily from L-alanine and its derivatives. Both pyruvate and L-alanine were decarboxylated prior to label incorporation into lipid in the testis and thoracic tissue.

Sterol and fatty acid synthesis in developing brains of three myelin-deficient mouse mutants

1. 1. The rate of sterol synthesis and the level of hydroxymethylglutaryl-CoA (HMG-CoA) reductase were previously shown to be subnormal in the myelin-deficient brains of jimpy ( jp/Y) mutants. To determine whether these changes were specific for the jimpy mutation, rates of sterol synthesis and other aspects of lipid synthesis in jimpy brains were compared with those in the brains of two other mutants with defective myelination of the central nervous system, quaking ( qk/qk) and myelin synthesis deficiency ( msd/Y). 2. 2. The rate of sterol synthesis from [1- 14C]acetate or from [2- 14C]mevalonic acid and the level of HMG-CoA reductase were depressed in all three mutations at the earliest age at which clinical symptoms of the disorders were apparent. Ratios of cholesterol to desmosterol in developing brains of the three mutations were normal. 3. 3. The heat stability and the K m (HMG-CoA) of brain HMG-CoA reductase were not affected by the three mutations. 4. 4. The rate of fatty acid synthesis from [1- 14C]acetate was depressed in qk/qk brains but not in jp/Y or msd/Y brains. 5. 5. Rates of sterol, fatty acid, and CO 2 production in brain were not reduced in two neuromuscular mutants (reeler ( rl/rl) and oscillator ot/ot) with depressed growth rates but without known myelin deficiencies or in normal immature mice deprived of food, indicating that inadequate nutrition was not a cause for the observed deficiencies in lipid synthesis rates.

Hodgkin's disease terminating in acute lymphosarcoma cell leukemia.A metabolic study

A 40-year-old woman with Hodgkin's disease developed clinical signs of acute leukemia during the fourth year of her illness. She had been treated for Hodgkin's disease with supervoltage radiation therapy and extensive cytotoxic drug therapy. Metabolic studies of her abnormal leukocytes, using 14C-labeled glucose and propionate, confirmed the clinical impression that this was a lymphosarcoma cell leukemia. The development of acute leukemia secondary to radiation and cytotoxic therapy was considered, but the possibility that the lymphosarcoma cell leukemia was a terminal transition of the Hodgkin's disease was also raised. These lymphosarcoma cells also had a more rapid rate of incorporation of thymidine-C3H3 into DNA and a higher rate of lipid synthesis from 14C-labeled acetate than those cells recovered from lymphosarcoma cell leukemias studied previously. Leukocytes from this patient and those from another with acute leukemia may exemplify a characteristic metabolic pattern typical of the acute form of lymphosarcoma cell leukemia.

Effect of cell size on lipid synthesis by human adipose tissue in vitro

When adipose tissue cells were incubated with collagenase for different periods of time, cell populations with different mean cell sizes were obtained from the same tissue sample. Lipid synthesis from glucose was studied as a function of adipose cell size and number. The incubations were performed in Parker medium 199, which is suitable for tissue culture of human adipose tissue. The results show that the larger cells of a specimen have a greater rate of lipid synthesis than the smaller cells of the same specimen. This is mainly due to an increase in the synthesis of glyceride-glycerol. Addition of insulin stimulated lipid synthesis. However, the larger adipose cells were less sensitive to the stimulating effect of insulin than the smaller cells.

Some aspects of lipid and protein metabolism in developing rat optic nerves

(1) Optic nerves from different ages of rats were incubated in a tissue culture medium in vitro containing either a lipid precursor (radioactive acetate) or a labelled amino acid (glycine). The total lipid or protein was extracted separately and the specific activity of the respective fractions was measured. (2) The specific activity of the lipid and protein fractions was significantly higher in the half of the nerve nearest this orbit (the intraorbital end) compared with the intracranial end. (3) At all ages of rats the rate of lipid synthesis in the optic nerve in vitro is directly proportional to the rate of protein synthesis. (4) The logarithm of the specific activity of both the lipid and the protein fractions was inversely proportional to the length of the optic nerve. (5) The specific activity of the lipid and protein fractions of the optic nerve decline during post-natal life. (6) Expressing the specific activity of the lipid fraction in the nerve against the nuclear population (counts/sec/nucleus) gives an index of the rate of myelination. This index remained at a constant level from approximately 20 to 70 days after which time it declined to less than half that in the fully adult animal. .

Lipogenesis in adipose tissue from genetically obese rats

Lipogenesis by adipose tissue and liver from lean, genetic obese and control obese rats was studied in vitro. More palmitate-1- 14C was incorporated into lipid by adipose tissue of genetically obese rats than by control tissues. Glucose enhanced this effect but glycerol did not. Adipose tissue from genetic obese rats incorporated significantly more radioactivity from glycerol- 14C into glycerideglycerol than adipose tissue from hypothalamic-obese rats in the presence of glucose and epinephrine. In homogenates of fat from genetic obese rats the addition of glycerol-3-phosphate stimulated a greater rate of lipid synthesis than in homogenates from lesioned-obese rats.

Fatty acid biosynthesis in the silkmoth, Hyalophora cecropia

Gas chromatographic and mass spectrographic analysis established that the six major fatty acids of Hyalophora cecropia are palmitic, palmitoleic, stearic, oleic, linoleic, and linolenic acids. Radiotracer studies at several developmental stages reveal that H. cecropia can synthesize only straight-chain saturated and mono-unsaturated fatty acids from acetate. This insect does have the capacity to lengthen palmitic acid to stearic acid and can dehydrogenate both to the corresponding monoenes. The data demonstrate that the rates of lipid synthesis from acetate, distribution of label among various fatty acids, chain lengthening, and desaturation are functions of developmental stage. An analysis of our data and that in the literature suggests that no insect has been shown to synthesize polyenoic acids or can synthesize monoenoic acids other than by direct desaturation of existing or newly synthesized saturated fatty acids.

Lipid metabolism in normal and rachitic rat epiphyseal cartilage.

SummaryLipid synthesis in rat epiphyseal cartilage has been studied in relation to normal growth and the production of rickets. Cartilage was incubated in vitro in modified Krebs-Ringer bicarbonate buffer with added I-14C palmitic acid. In normal 28-day-old male weanling rats, the total uptake of 1-14C palmitic acid from the media showed a gradual increase with time. Fractionation of the lipids showed 64.6% of the label in free fatty acids; 19.2% in triglycerides; 12.8% in phospholipids; and 6.2% in cholesterol and cholesterol esters. In rachitic rats of comparable age, the total uptake of 1-14C palmitic acid was increased significantly, indicating an increased rate of lipid synthesis.

Alterations in lipid metabolism associated with premolt activity in a land crab and fresh-water crayfish

1. 1. The initiation of premolt activity results in an increased lipid content in the hepatopancreas of both Orconectes virilis (fresh-water cryafish) and Gecarcinus lateralis (land crab) and an increase in the lipid content of the abdominal muscle of O. virilis. 2. 2. The increased lipid content of the hepatopancreas reflects and increased incorporation of lipid precursors into both the neutral lipid and phospholipid fractions of this tissue during premolt. 3. 3. Although the ratio of neutral lipid to phospholipid changes following the induction of premolt activity, the fatty acid compositions of these two fractions are remarkably similar in intermolt and premolt animals. 4. 4. The increase in the rate of lipid synthesis which results from eyestalk extirpation is partially negated by the administration of a saline eyestalk extract.

Lipid accretion in the perfused rabbit aorta

Summary A technique of in situ perfusion of rabbit abdominal aorta permitted measurement of rates of aortic lipid synthesis in conditions approaching the physiological. Aortic synthesis of fatty acids proceeded by both chain elongation and de novo pathways. Fatty acids synthesised in aorta from glucose were a quantitatively unimportant source of aortic lipid whereas perfusate free fatty acids were rapidly incorporated into aortic ester lipid. Aortic lipid glycerol was synthesised from labelled glucose and more than 96 % of the label in aortic lipid was in non-fatty acid moieties. While tri- and diglycerides were synthesised in aorta from perfusate glucose and free fatty acids, aortic phospholipids were the major ester-product (> 56 %) of these substrates. Phosphatidylcholine was the major phospholipid synthesised and was formed by de novo synthesis although data was also compatible with the presence of a lysophosphatide pathway in intima. Phosphatidylinositol was rapidly synthesised and glucose carbon entered glycerol but not inositol of this lipid. The possibility of contamination of aortic lipid with radioactive lipid from periaortic adipose tissue was emphasised by the demonstration that rates of lipid synthesis from various substrates were 30–400 times greater in periaortic adipose tissue than in aorta.

Influence of Caffeine-containing Beverages on the Growth, Food Utilization and Plasma Lipids of the Rat

It has been suggested that coffee-drinking may be a factor in the causation of cardiovascular disease, and tea drinking a factor in its prevention. In the present study, freeze-dried tea, decaffeinated coffee, coffee and pure caffeine were fed to rats, for 54 days, in a starch-based diet devoid of recognized atherogenic agents. None of the dietary supplements affected growth rate, the efficiency of food conversion or the weights of the organs. Changes produced in the plasma lipid values were proportional to the caffeine content of the diets. With increasing intake of caffeine, plasma cholesterol and phospholipid concentrations rose, while the triglyceride concentration fell. Feeding sucrose affected the plasma lipids in the opposite direction; triglycerides were increased whereas cholesterol and phospholipids were unaltered. This difference in response is attributed to a difference in the rate of lipid synthesis in the liver. The activity of pyruvate kinase, which was used as an index of lipogenesis, was unaffected by coffee, but was doubled by the substitution of sucrose for starch in the diet. Results are discussed briefly in relation to current views on the role of plasma lipids in atherogenesis.

The Effect of Prolonged Incubation on Lipid Synthesis by Rat Adipose Tissue

Abstract Prolonged incubation (6 hours) of adipose tissue from fed and 48-hour-fasted rats resulted in an increased rate of synthesis of fatty acids and glyceride glycerol from glucose uniformly labeled with 14C. However, lipogenesis from acetate-1-14C was increased by prolonged incubation in tissues from fasted animals only. These changes in the rate of lipid synthesis were not attributable to alterations in the content of free fatty acid in the tissue during incubation. The effect of prolonged incubation was demonstrable only in the absence of insulin or when very low concentrations were added. This was masked in the presence of a high concentration of insulin. Prolonged incubation increased the rate of glucose entry, as indicated by the more rapid accumulation of the nonmetabolizable sugar 3-O-methylglucose. It is concluded that the increase in utilization of glucose for lipid synthesis following prolonged incubation can be accounted for by the increased rate of glucose entry into the cells.

Cyclic variation of uterine metabolic activity in the golden hamster.

Changes in uterine metabolism which occur during the normal estrous cycle of the golden hamster have been evaluated. Between days 2 and 4 of the cycle there is an increase in activity of glucose-6-phosphate dehydrogenase, rate of 14CO2 production from labeled glucose, proportion of glucose being metabolized via the hexose monophosphate pathway (C-l/C-6 ratio) and incorporation of 14C from glucose-6-14C into lipid, protein and DNA. Increase in C-l/C-6 ratio is highly correlated with the rate of lipid synthesis. These increases parallel the rising estrogen level occurring at this time and closely resemble those seen in the uterus of the mature ovariectomized rat after administration of 5.0 μg of estradiol-17β. (Endocrinology 80: 714, 1967)

Comparison of serum total lipid during cold exposure in hibernating and non-hibernating mammals.

LIPID metabolism in mammals has been widely investigated with reference to cold acclimation and hibernation. In this laboratory, work on lipid metabolism is hamsters during cold exposure and hibernation has been focused on rates of lipid synthesis or utilization in tissues in vitro. This communication is concerned with measurement of the circulating total lipid in the intact animal. Analyses were performed on blood from, cold-exposed and hibernating golden hamsters (Mesocricetus auratus). A similar series of analyses were performed on white Wistar rats to provide comparison with a non-hibernating mammal. Blood samples were taken from animals kept at room temperature as control, and kept in the cold (5° ± 1° C) for 48 h, 3 weeks or 6–8 weeks. Samples were also taken from hamsters in hibernation, arousing from hibernation (cheek pouch temperature 18°–20° C) and immediately after the animals regained full consciousness and normal temperature. The animals were stunned by a sharp blow on the head, except those in hibernation. Approximately 2 c.c. of blood were withdrawn by cardiac puncture. After removal of the needle the syringe was discharged into a centrifuge tube and the sample allowed to clot. The samples were centrifuged and the serum removed by suction. The serum was then analysed for total lipid by a colorimetric method employing Sudan black B, described by Swahn1. The samples were compared with a standard of corn oil in ethanol. The concentrations were calculated as mg total lipid/100 ml. of serum. The results are shown in Fig. 1.

Utilization of fatty acids by rat liver slices as a function of medium concentration

The rate of incorporation of palmitate-1-C14 into neutral lipids and phospholipids of rat liver slices in vitro and its conversion to C14O2 were shown to increase markedly as the free fatty acid (FFA) concentration of the medium was increased. Incorporation into lipids and conversion to C14O2 proceeded linearly with time over 60 min. The incorporation of glycerol-1,3-C14 into neutral lipids also increased as the FFA concentration of the medium was increased but incorporation into phospholipids was unchanged. It is concluded that high FFA concentrations cause a true increase in rate of neutral lipid synthesis by liver slices. The associated increase in incorporation of labeled palmitate into phospholipids most likely reflects the higher specific radioactivity of the precursor pool of FFA and/or an exchange reaction rather than a true increase in net synthesis. A method for recovering tissue FFA quantitatively is described. Normal liver was found to contain 0.40–0.87 µEq FFA/g wet wt. The composition of this tissue FFA fraction is presented.

Leucocyte lipid metabolism in myeloproliferative states.

SummaryLipid synthesis in human leucocytes was examined in vitro in blood from patients with myeloproliferative states and from normal controls, acetate being used as substrate. The incorporation of acetate‐1‐C14 was measured in total lipids, neutral lipids and phospholipids of the leucocytes and plasma. There was a low rate of total lipid synthesis in polycythæmia vera, but the relative rates of incorporation of radioactivity into lipid fractions were normal. Lipid synthesis in myelosclerosis was similar to that in the controls with the exception of one case, in which a very high rate was observed, and in which incorporation of radioactivity into phospholipids was disproportionately increased. These results are discussed in relation to cell age and to leucocyte lipid synthesis in myeloid leukæmia.