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

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.

1967 ◽  
Vol 45 (2) ◽  
pp. 201-214 ◽  
Author(s):  
Gilbert A. Leveille

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.


1985 ◽  
Vol 40 (11-12) ◽  
pp. 917-918 ◽  
Author(s):  
Uwe Homeyer ◽  
D. Schulze-Siebert ◽  
G. Schultz

Abstract In vitro incubation of intact spinach chloroplasts with 1 mᴍ Pyruvate was used to study the specificity of action of the herbicide Chlorsulfuron on the synthesis of valine, alanine and fatty acids. As a result, increasing concentrations of the herbicide strongly inhibited valine synthesis while fatty acid synthesis via pyruvate dehydrogenase complex (PDC) and alanine formation by transamination reaction was promoted.


2013 ◽  
Vol 57 (11) ◽  
pp. 5729-5732 ◽  
Author(s):  
Joshua B. Parsons ◽  
Matthew W. Frank ◽  
Jason W. Rosch ◽  
Charles O. Rock

ABSTRACTInactivation of acetyl-coenzyme A (acetyl-CoA) carboxylase confers resistance to fatty acid synthesis inhibitors inStaphylococcus aureuson media supplemented with fatty acids. The addition ofanteiso-fatty acids (1 mM) plus lipoic acid supports normal growth of ΔaccDstrains, but supplementation with mammalian fatty acids was less efficient. Mice infected with strain RN6930 developed bacteremia, but bacteria were not detected in mice infected with its ΔaccDderivative.S. aureusbacteria lacking acetyl-CoA carboxylase can be propagatedin vitrobut were unable to proliferate in mice, suggesting that the acquisition of inactivating mutations in this enzyme is not a mechanism for the evasion of fatty acid synthesis inhibitors.


1975 ◽  
Vol 150 (3) ◽  
pp. 441-451 ◽  
Author(s):  
S R Sooranna ◽  
E D Saggerson

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.


1970 ◽  
Vol 118 (2) ◽  
pp. 259-263 ◽  
Author(s):  
Alan G. Goodridge

1. A single glucose meal stimulated the incorporation of acetate into fatty acids in liver slices. If the glucose was added in vitro, it had no effect. Fructose and glycerol in vitro markedly stimulated fatty acid synthesis from acetate. Fructose and glycerol probably by-passed a rate-controlling reaction between glucose and triose phosphate. This reaction may have been stimulated by glucose administered in vivo. 2. The stimulation of fatty acid synthesis caused by fructose did not require the synthesis of enzyme, thus indicating that fatty acid-synthesizing enzymes were present in a latent form in the livers from unfed chicks.


1986 ◽  
Vol 41 (1-2) ◽  
pp. 169-171 ◽  
Author(s):  
Hans Kleinig ◽  
Peter Beyer ◽  
Carmen Schubert ◽  
Bodo Liedvogel ◽  
Friedhelm Lütke-Brinkhaus

Abstract The fatty acid pattern of Cyanophora paradoxa membrane lipids is highly unusual with 16:0, 20:3 and 20:4 as the main acids. The 20:4 acid is preferentially distributed among the cyanelle lipids. In isolated cyanelles a relatively low in vitro synthesis of only saturated and monounsatu­rated fatty acids from [l-14C]acetate was observed which corresponds to the relatively low photo­synthetic oxygen evolution.


1977 ◽  
Vol 232 (4) ◽  
pp. E358
Author(s):  
R M Evans ◽  
R W Scholz

Incorporation of tritiated water into fatty acids by rat adipose tissue and lung tissue slices incubated with 5 mM glucose indicated a level of fatty acid synthesis in rat lung approximately 15% that observed in adipose tissue in vitro. (-)-Hydroxycitrate, and inhibitor of ATP citrate lyase, markedly reduced tritiated water incorporation into fatty acids by lung tissue slices. The effects of (-)-hydroxycitrate and n-butymalonate on the incorporation of 14C-labeled glucose, pyruvate, acetate, and citrate suggested that citrate is a major acetyl carrier for de novo fatty acid synthesis in lung tissue. Alternative mechanisms to citrate as an acetyl carrier were also considered. Lung mitochondrial preparations formed significant levels of acetylcarnitine in the presence of pyruvate and carnitine. However, the effect of carnitine on the incorporation of 14C-labeled glucose, pyruvate, acetate, and citrate into fatty acids by lung tissue slices indicated that acetylcarnitine may not be a significant acetyl carrier for fatty acid synthesis but may serve as an acetyl "buffer" in the control of mitochondrial acetyl-CoA levels. Additionally, it appears unlikely that either acetylaspartate or acetoacetate are of major importance in acetyl transfer in lung tissue.


1972 ◽  
Vol 129 (4) ◽  
pp. 929-935 ◽  
Author(s):  
Isabel A. Forsyth ◽  
Christopher R. Strong ◽  
Raymond Dils

1. The rate of fatty acid synthesis by mammary explants from rabbits pregnant for 16 days or from rabbits pseudopregnant for 11 days was stimulated up to 15-fold by culturing for 2–4 days with prolactin. This treatment initiated the predominant synthesis of C8:0 and C10:0 fatty acids, which are characteristic of rabbit milk. 2. Inclusion of insulin in the culture medium increased the rate of synthesis of these medium-chain fatty acids. By contrast the inclusion of corticosterone led to the predominant synthesis of long-chain fatty acids. When explants were cultured for 2–4 days with insulin, corticosterone and prolactin, the rate of fatty acid synthesis increased up to 42-fold, but both medium- and long-chain fatty acids were synthesized. 3. These results show that the stimulus to mammary-gland lipogenesis and the initiation of synthesis of medium-chain fatty acids observed between days 16 and 23 of pregnancy in the rabbit can be simulated in vitro by prolactin alone. 4. When mammary explants from rabbits pregnant for 23 days were cultured for 2 days with insulin, corticosterone and prolactin, the rate of fatty acid synthesis increased fivefold, but there was a preferential synthesis of long-chain fatty acids. Culture with prolactin alone had little effect on the rate or pattern of fatty acids synthesized. 5. The results are compared with findings in vivo on the control of lipogenesis in the rabbit mammary gland, and are contrasted with the known effects of hormones in vitro on the mammary gland of the mid-pregnant mouse.


1971 ◽  
Vol 49 (6) ◽  
pp. 736-741 ◽  
Author(s):  
M. L. Halperin

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).


1968 ◽  
Vol 108 (1) ◽  
pp. 147-152 ◽  
Author(s):  
Ajit Goswami ◽  
James K. Skipper ◽  
William L. Williams

RNA from testes of hypophysectomized rats treated with follicle-stimulating hormone and luteinizing hormone markedly stimulates in vitro the incorporation of acetate and malonate (as CoA derivatives) into polyunsaturated fatty acids. The system in vitro contains the components necessary for both protein and fatty acid synthesis. That the RNA is a hormone-induced messenger type that causes enzyme synthesis that then causes fatty acid synthesis is supported by the following observations: (1) the stimulation of RNA synthesis by follicle-stimulating hormone and luteinizing hormone is decreased by injection of the animals with actinomycin D; (2) puromycin in the system in vitro decreases the synthesis of polyunsaturated fatty acids; (3) the activity of the RNA preparation is destroyed by digestion with ribonuclease; in fact, the digest is inhibitory, which is a characteristic of messenger-RNA-mediated protein synthesis; (4) protein that might be denatured enzyme is virtually absent from the effective RNA preparations.


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