FATTY ACID AND GLYCERIDE GLYCEROL SYNTHESIS FROM GLUCOSE DURING HIGH RATES OF GLUCOSE UPTAKE IN THE INTACT RAT

1965 ◽  
Vol 43 (4) ◽  
pp. 437-450 ◽  
Author(s):  
A. S. W. de Freitas ◽  
Florent Depocas
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Glucose Uptake ◽  
Fatty Acid Synthesis ◽  
Acid Synthesis ◽  
Component Fatty Acid ◽  
Rat Tissues ◽  
Total Lipids ◽  
Glucose Carbon ◽  
Total Glucose

The extent of incorporation of glucose carbon into total lipids and component fatty acid, neutral glyceride glycerol, and phosphoglyceride glycerol moieties of carcass, liver, and epididymal tissue has been measured in 20 rats under conditions of constant plasma glucose concentration and specific activity. Rates of fatty acid synthesis from glucose and absolute rates of synthesis have also been estimated. Each rat received 750 mg glucose per hour by continuous infusion. The incorporation of glucose carbon into carcass, liver, and epididymal fat was, respectively, 6.2, 0.75, and 0.06% of the total glucose carbon taken up by the rat tissues. Fifty percent of the C14 found in total lipids of carcass and liver was in the fatty acid fraction. Corresponding glyceride glycerol moieties contained approximately 40% of the total activity. The low level of incorporation of glucose carbon into fatty acids and glyceride glycerol indicates that lipogenesis from glucose can only account for a small proportion of the total glucose taken up by the tissues, even at high rates of glucose uptake. Rates of synthesis from glucose of carcass and liver fatty acids were estimated as 1.5 and 0.11 mmoles fatty acid per tissue per day respectively, with corresponding half-lives of 57 and 7.6 days. Absolute rates of fatty acid synthesis were estimated as 2.6 and 0.55 mmoles fatty acid per day for carcass and liver tissue respectively, with corresponding half-lives of 34 and 4.6 days.

scholarly journals Synthesis of fatty acids in the perfused mouse liver

1974 ◽  
Vol 142 (3) ◽  
pp. 611-618 ◽  
Author(s):  
D. Michael W. Salmon ◽  
Neil L. Bowen ◽  
Douglas A. Hems
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
De Novo ◽  
Saturated Fatty Acids ◽  
Carbon Sources ◽  
Acid Synthesis ◽  
Hepatic Glycogen ◽  
Total Rate ◽  
Glucose Carbon

1. Fatty acid synthesis de novo was measured in the perfused liver of fed mice. 2. The total rate, measured by the incorporation into fatty acid of3H from3H2O (1–7μmol of fatty acid/h per g of fresh liver), resembled the rate found in the liver of intact mice. 3. Perfusions with l-[U-14C]lactic acid and [U-14C]glucose showed that circulating glucose at concentrations less than about 17mm was not a major carbon source for newly synthesized fatty acid, whereas lactate (10mm) markedly stimulated fatty acid synthesis, and contributed extensive carbon to lipogenesis. 4. The identification of 50% of the carbon converted into newly synthesized fatty acid lends further credibility to the use of3H2O to measure hepatic fatty acid synthesis. 5. The total rate of fatty acid synthesis, and the contribution of glucose carbon to lipogenesis, were directly proportional to the initial hepatic glycogen concentration. 6. The proportion of total newly synthesized lipid that was released into the perfusion medium was 12–16%. 7. The major products of lipogenesis were saturated fatty acids in triglyceride and phospholipid. 8. The rate of cholesterol synthesis, also measured with3H2O, expressed as acetyl residues consumed, was about one-fourth of the basal rate of fatty acid synthesis. 9. These results are discussed in terms of the carbon sources of hepatic newly synthesized fatty acids, and the effect of glucose, glycogen and lactate in stimulating lipogenesis, independently of their role as precursors.

scholarly journals Interrelationship and control of glucose metabolism and lipogenesis in isolated fat-cells. Effect of the amount of glucose uptake on the rates of the pentose phosphate cycle and of fatty acid synthesis

1972 ◽  
Vol 128 (5) ◽  
pp. 1089-1096 ◽  
Author(s):  
H. Kather ◽  
M. Rivera ◽  
K. Brand
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Fatty Acid Synthesis ◽  
Acid Synthesis ◽  
Pentose Phosphate ◽  
Fat Cells ◽  
Pentose Phosphate Cycle ◽  
Wide Range

In order to study the quantitative relationship between fatty acid synthesis and pentose phosphate-cycle activity under different hormonal and dietary conditions affecting the extent of glucose uptake, cells isolated from rat epididymal adipose tissue were incubated in bicarbonate buffer containing [U-14C]-, [1-14C]- or [6-14C]-glucose. From the amount of glucose taken up, the production of lactate and pyruvate, and the incorporation of 14C from differently labelled [14C]glucose into CO2, fatty acids and glyceride glycerol, the rates of glucose metabolism via different pathways and the extent of lipogenesis under various experimental conditions were determined. The contribution of the pentose phosphate-cycle to glucose metabolism under normal conditions was calculated to be 8%. Starvation and re-feeding, and the presence of insulin, caused an enhancement of glucose uptake, pentose phosphate-cycle activity and fatty acid synthesis. Plots of both pentose phosphate-cycle activity and fatty acid synthesis versus glucose uptake revealed that the extent of glucose uptake, over a wide range, determines the rates of fatty acid synthesis and glucose metabolism via the pentose phosphate cycle. A balance of formation and production of nicotinamide nucleotides in the cytoplasm was established. The total amount of cytoplasmic NADH and NADPH formed was only in slight excess over the hydrogen equivalents required for the synthesis of fatty acids, glyceride glycerol and lactate. Except in cells from starved animals, the pentose phosphate cycle was found to provide only about 60% of the NADPH required for fatty acid synthesis. The results are discussed with respect to an overall control of the different metabolic and biosynthetic reactions in the fat-cells by the amount of glucose transported into the cell.

scholarly journals The regulation of glyceride synthesis in isolated white-fat cells. The effects of palmitate and lipolytic agents

1972 ◽  
Vol 128 (5) ◽  
pp. 1057-1067 ◽  
Author(s):  
E. D Saggerson
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Free Fatty Acids ◽  
Fatty Acid Synthesis ◽  
Acid Synthesis ◽  
Fat Cells ◽  
Glyceride Synthesis ◽  
Glucose Incorporation ◽  
High Concentrations ◽  
Stimulation Of

1. 0.5mm-Palmitate stimulated incorporation of [U-14C]glucose into glyceride glycerol and fatty acids in normal fat cells in a manner dependent upon the glucose concentration. 2. In the presence of insulin the incorporation of 5mm-glucose into glyceride fatty acids was increased by concentrations of palmitate, adrenaline and 6-N-2′-O-dibutyryladenosine 3′:5′-cyclic monophosphate up to 0.5mm, 0.5μm and 0.5mm respectively. Higher concentrations of these agents produced progressive decreases in the rate of glucose incorporation into fatty acids. 3. The effects of palmitate and lipolytic agents upon the measured parameters of glucose utilization were similar, suggesting that the effects of lipolytic agents are mediated through increased concentrations of free fatty acids. 4. In fat cells from 24h-starved rats, maximal stimulation of glucose incorporation into fatty acids was achieved with 0.25mm-palmitate. Higher concentrations of palmitate were inhibitory. In fat cells from 72h-starved rats, palmitate only stimulated glucose incorporation into fatty acids at high concentrations of palmitate (1mm and above). 5. The ability of fat cells to incorporate glucose into glyceride glycerol in the presence of palmitate decreased with increasing periods of starvation. 6. It is suggested that low concentrations of free fatty acids stimulate fatty acid synthesis from glucose by increasing the utilization of ATP and cytoplasmic NADH for esterification of these free fatty acids. When esterification of free fatty acids does not keep pace with their provision, inhibition of fatty acid synthesis occurs. Provision of free fatty acids far in excess of the esterification capacity of the cells leads to uncoupling of oxidative phosphorylation and a secondary stimulation of fatty acid synthesis from glucose.

EFFECT OF ALLOXAN, INSULIN, AND THYROXINE ON CHOLESTEROL AND FATTY ACID SYNTHESIS BY RAT LIVER HOMOGENATES

1957 ◽  
Vol 35 (1) ◽  
pp. 15-23 ◽  
Author(s):  
J. F. Scaife ◽  
B. B. Migicovsky
Keyword(s):  
Carbon Dioxide ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Rat Liver ◽  
Fatty Acid Synthesis ◽  
Sodium Acetate ◽  
Cholesterol Synthesis ◽  
Acid Synthesis ◽  
Liver Homogenates ◽  
Vitro Effect

The in vitro effect of alloxan and insulin on the synthesis of cholesterol and fatty acids from 1-C14-sodium acetate by rat liver homogenates has been examined. Alloxan caused a reduction in the incorporation of acetate into cholesterol, fatty acids, and C14O2, but an increase in the oxygen consumption and carbon dioxide production. The addition of insulin to homogenates caused a reduction in cholesterol synthesis but an increase in fatty acid synthesis both for normal and diabetic animals. Homogenates from thyrotoxic rats exhibited a marked reduction in cholesterol synthesis when compared with normal animals. C14O2 production by homogenates from starved rats was appreciably lower than for those from normal animals. With this exception no appreciable difference was found in the oxygen uptake, carbon dioxide, or C14O2 production in homogenates from normal, starved, thyroxine-treated, or diabetic animals. Synthesized cholesterol was found to be located principally in the particulate matter of the homogenates after they had been incubated with 1-C14-sodium acetate. Homogenates from starved rats showed no greater tendency to degrade preformed cholesterol during incubation than did those from normal rats.

Effect of glucose concentration in the growth medium on the synthesis of fatty acids by the yeast Candida bogoriensis

1982 ◽  
Vol 28 (2) ◽  
pp. 223-230 ◽  
Author(s):  
Adrian J. Cutler ◽  
Robley J. Light
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Yeast Extract ◽  
Fatty Acid Synthesis ◽  
Acid Synthesis ◽  
Glucose Medium ◽  
Triglyceride Fraction ◽  
Low Glucose ◽  
Stimulation Of

The yeast Candida bogoriensis produced large quantities of an extracellular glycolipid, the diacetyl sophoroside of 13-hydroxydocosanoic acid, when grown on a standard glucose rich medium (3% glucose, 0.15% yeast extract), but not when grown on a low glucose medium (0.5% glucose, 0.4% yeast extract) (A. J. Cutler and R. J. Light. 1979. J. Biol. Chem. 254: 1944–1950). Glucose levels also affected the quantity and distribution of the free fatty acid and triglyceride fractions synthesized by this organism. Cells grown on the low glucose medium contained palmitate and stearate as the major fatty acids in these two fractions, and a 3-h incubation with [1-14C]acetate led primarily to the labeling of these two acids. Cells grown on the standard enriched glucose medium contained relatively less stearate and more behenate than the low glucose grown cells, and the incorporation of [1-14C]acetate into stearate was decreased, while that into behenate was increased.Supplementation of low glucose grown cells with glucose led to a rapid stimulation of fatty acid synthesis, primarily palmitate and stearate in the free fatty acid fraction and stearate in the triglyceride fraction. Total triglyceride began to increase a few hours after supplementation, but synthesis of the extracellular glycolipid, and hence 13-hydroxydocosanoic acid, did not occur until 12–24 h after supplementation. The stimulation by glucose of long chain fatty acid synthesis in C. bogoriensis was therefore a process distinct from the glucose stimulation of palmitate and stearate synthesis, though the two events may be causally related.

scholarly journals Role of peroxisome proliferator-activated receptor-α on the synthesis of monounsaturated fatty acids in goat mammary epithelial cells

2020 ◽  
Vol 98 (3) ◽  
Author(s):  
Huibin Tian ◽  
Jun Luo ◽  
Hengbo Shi ◽  
Xiaoying Chen ◽  
Jiao Wu ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Mammary Epithelial Cells ◽  
Acid Synthesis ◽  
Mammary Epithelial ◽  
Mrna Abundance ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Goat Mammary Epithelial Cells

Abstract A key member of the nuclear receptor superfamily is the peroxisome proliferator-activated receptor alpha (PPARA) isoform, which in nonruminants is closely associated with fatty acid oxidation. Whether PPARA plays a role in milk fatty acid synthesis in ruminants is unknown. The main objective of the present study was to use primary goat mammary epithelial cells (GMEC) to activate PPARA via the agonist WY-14643 (WY) or to silence it via transfection of small-interfering RNA (siRNA). Three copies of the peroxisome proliferator-activated receptor response element (PPRE) contained in a luciferase reporter vector were transfected into GMEC followed by incubation with WY at 0, 10, 20, 30, 50, or 100 µM. A dose of 50 µM WY was most effective at activating PPRE without influencing PPARA mRNA abundance. Transfecting siRNA targeting PPARA decreased its mRNA abundance to 20% and protein level to 50% of basal levels. Use of WY upregulated FASN, SCD1, ACSL1, DGAT1, FABP4, and CD36 (1.1-, 1.5-, 2-, 1.4-, 1.5-, and 5-fold, respectively), but downregulated DGAT2 and PGC1A (−20% and −40%, respectively) abundance. In contrast, triacylglycerol concentration decreased and the content and desaturation index of C16:1 and C18:1 increased. Thus, activation of PPARA via WY appeared to channel fatty acids away from esterification. Knockdown of PPARA via siRNA downregulated ACACA, SCD1, AGPAT6, CD36, HSL, and SREBF1 (−43%, −67%, −16%, −56%, −26%, and −29%, respectively), but upregulated ACSL1, DGAT2, FABP3, and PGC1A (2-, 1.4-, 1.3-, and 2.5-fold, respectively) mRNA abundance. A decrease in the content and desaturation index of C16:1 and C18:1 coupled with an increase in triacylglycerol content accompanied those effects at the mRNA level. Overall, data suggest that PPARA could promote the synthesis of MUFA in GMEC through its effects on mRNA abundance of genes related to fatty acid synthesis, oxidation, transport, and triacylglycerol synthesis.

scholarly journals Fatty acid synthesis is a target for antibacterial activity of unsaturated fatty acids

FEBS Letters ◽  
2005 ◽  
Vol 579 (23) ◽  
pp. 5157-5162 ◽  
Author(s):  
Chang Ji Zheng ◽  
Jung-Sung Yoo ◽  
Tae-Gyu Lee ◽  
Hee-Young Cho ◽  
Young-Ho Kim ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Antibacterial Activity ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Unsaturated Fatty Acids ◽  
Acid Synthesis

Fatty acid synthesis: from CO2 to functional genomics

2000 ◽  
Vol 28 (6) ◽  
pp. 567-574 ◽  
Author(s):  
J. Ohlrogge ◽  
M. Pollard ◽  
X. Bao ◽  
M. Focke ◽  
T. Girke ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Regulatory Networks ◽  
Fatty Acid Synthase ◽  
Expression Patterns ◽  
Acid Synthesis ◽  
Acetyl Coa ◽  
Specific Expression ◽  
Direct Production

For over 25 years there has been uncertainty over the pathway from CO2, to acetyl-CoA in chloroplasts. On the one hand, free acetate is the most effective substrate for fatty acid synthesis by isolated chloroplasts, and free acetate concentrations reported in leaf tissue (0.1–1 mM) appear adequate to saturate fatty acid synthase. On the other hand, a clear mechanism to generate sufficient free acetate for fatty acid synthesis is not established and direct production of acetyl-CoA from pyruvate by a plastid pyruvate dehydrogenase seems a more simple and direct path. We have re-examined this question and attempted to distinguish between the alternatives. The kinetics of 13CO2 and 14CO2 movement into fatty acids and the absolute rate of fatty acid synthesis in leaves was determined in light and dark. Because administered 14C appears in fatty acids within < 2–3 min our results are inconsistent with a large pool of free acetate as an intermediate in leaf fatty acid synthesis. In addition, these studies provide an estimate of the turnover rate of fatty acid in leaves. Studies similar to the above are more complex in seeds, and some questions about the regulation of plant lipid metabolism seem difficult to solve using conventional biochemical or molecular approaches. For example, we have little understanding of why or how some seeds produce >50%, oil whereas other seeds store largely carbohydrate or protein. Major control over complex plant biochemical pathways may only become possible by understanding regulatory networks which provide ‘global’ control over these pathways. To begin to discover such networks and provide a broad analysis of gene expression in developing oilseeds, we have produced micro-arrays that display approx. 5000 seed-expressed Arabidopsis genes. Sensitivity of the arrays was 1–2 copies of mRNA/cell. The arrays have been hybridized with probes derived from seeds, leaves and roots, and analysis of expression ratios between the different tissues has allowed the tissue-specific expression patterns of many hundreds of genes to be described for the first time. Approx. 10% of the genes were expressed at ratios ≥ 10-fold higher in seeds than in leaves or roots. Included in this list are a large number of proteins of unknown function, and potential regulatory factors such as protein kinases, phosphatases and transcription factors. The arrays were also found to be useful for analysis of Brassica seeds.

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