FATTY ACID SYNTHESIS IN MAMMARY GLAND I. DIRECT INCORPORATION OF “DE NOVO” SYNTHESIZED MEDIUM CHAIN FATTY ACIDS INTO TRIACYLGLYCEROL

1981 ◽  
Vol 9 (2) ◽  
pp. 191P-191P
Author(s):  
Inger Grunnet ◽  
Jens Knudsen
1984 ◽  
Vol 220 (2) ◽  
pp. 513-519 ◽  
Author(s):  
H O Hansen ◽  
I Grunnet ◽  
J Knudsen

Goat mammary-gland microsomal fraction by itself induces synthesis of medium-chain-length fatty acids by goat mammary fatty acid synthetase and incorporates short- and medium-chain fatty acids into triacylglycerol. Addition of ATP in the absence or presence of Mg2+ totally inhibits triacylglycerol synthesis from short- and medium-chain fatty acids, and severely inhibits synthesis de novo of medium-chain fatty acids. The inhibition by ATP of fatty acid synthesis and triacylglycerol synthesis de novo can be relieved by glycerol 3-phosphate. The effect of ATP could not be mimicked by the non-hydrolysable ATP analogue, adenosine 5′-[beta, gamma-methylene]triphosphate and could not be shown to be caused by inhibition of the diacylglycerol acyltransferase by a phosphorylation reaction. Possible explanations for the mechanism of the inhibition by ATP are discussed, and a hypothetical model for its action is outlined.


1982 ◽  
Vol 202 (1) ◽  
pp. 139-143 ◽  
Author(s):  
J Knudsen ◽  
I Grunnet

1. Ruminant mammary-gland fatty acid synthetases can, in contrast with non-ruminant mammary enzymes, synthesize medium-chain fatty acids. 2. Medium-chain fatty acids are only synthesized in the presence of a fatty acid-removing system such as albumin, beta-lactoglobulin or methylated cyclodextrin. 3. The short- and medium-chain fatty acids synthesized were released as acyl-CoA esters from the fatty acid synthetase.


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.


2010 ◽  
Vol 299 (6) ◽  
pp. E918-E927 ◽  
Author(s):  
Michael C. Rudolph ◽  
Jenifer Monks ◽  
Valerie Burns ◽  
Meridee Phistry ◽  
Russell Marians ◽  
...  

The lactating mammary gland synthesizes large amounts of triglyceride from fatty acids derived from the blood and from de novo lipogenesis. The latter is significantly increased at parturition and decreased when additional dietary fatty acids become available. To begin to understand the molecular regulation of de novo lipogenesis, we tested the hypothesis that the transcription factor sterol regulatory element binding factor (SREBF)-1c is a primary regulator of this system. Expression of Srebf1c mRNA and six of its known target genes increased ≥2.5-fold at parturition. However, Srebf1c-null mice showed only minor deficiencies in lipid synthesis during lactation, possibly due to compensation by Srebf1a expression. To abrogate the function of both isoforms of Srebf1, we bred mice to obtain a mammary epithelial cell-specific deletion of SREBF cleavage-activating protein (SCAP), the SREBF escort protein. These dams showed a significant lactation deficiency, and expression of mRNA for fatty acid synthase ( Fasn), insulin-induced gene 1 ( Insig1), mitochondrial citrate transporter ( Slc25a1), and stearoyl-CoA desaturase 2 ( Scd2) was reduced threefold or more; however, the mRNA levels of acetyl-CoA carboxylase-1α ( Acaca) and ATP citrate lyase ( Acly) were unchanged. Furthermore, a 46% fat diet significantly decreased de novo fatty acid synthesis and reduced the protein levels of ACACA, ACLY, and FASN significantly, with no change in their mRNA levels. These data lead us to conclude that two modes of regulation exist to control fatty acid synthesis in the mammary gland of the lactating mouse: the well-known SREBF1 system and a novel mechanism that acts at the posttranscriptional level in the presence of SCAP deletion and high-fat feeding to alter enzyme protein.


1993 ◽  
Vol 48 (7-8) ◽  
pp. 616-622 ◽  
Author(s):  
Jochen Fuhrmann ◽  
Klaus-Peter Heise

Abstract The colorless embryos of Cuphea wrightii A. Gray accumulate capric (about 30%) and lauric acid (about 50%) in their storage lipids. Fractionation studies show that the capacities for the synthesis of these medium-chain fatty acids (MCFA) from [1-14C]acetate were strictly bound to intact plastids. These, in turn, obligately required the addition of ATP. ATP could partially be substituted by ADP. Reduction of the pyridine nucleotide pool, required for opti­mum MCFA formation within the plastids, was driven by glucose 6-phosphate. Under these conditions the plastids were capable of synthesizing MCFA like the intact tissue. The presence of CoA in the incubation medium induced acyl-CoA formation. The observed accumulation of unesterified capric and lauric acid in the absence of CoA suggests that acyl-ACP thioesterase activity is involved in the chain termination. Treatment with cerulenin led to an unexpectedly small reduction of total fatty acid synthesis while the chain elongation of capric acid was clearly inhibited. A similar accumulation of capric acid at the expense of longer chain fatty acids has been observed after replacing ATP by ADP. These findings implicate that even the condensing enzymes are involved in the control of chain ter­mination.


1958 ◽  
Vol 149 (936) ◽  
pp. 414-420

1. Introduction: The role of acetate in fatty-acid synthesis In 1945 Folley and his colleagues (see Foiley 1949, 1952; Malpress 1946) suggested that, in the ruminant, short-chain fatty acids might be synthesized by the lactating mammary gland from acetate. These short-chain fatty acids might then serve as precursors for the synthesis of long-chain acids. Folley & French (1949, 1950) showed that in vitro slices of lactating ruminant mammary gland were able to synthesize fat from acetate, as indicated by a respiratory quotient greater than unity. Non-ruminant lactating mammary tissue was unable to do so, but could utilize glucose for fat synthesis. It was later shown, with the aid of tracers (Balmain, Folley & Glascock 1954) that non-ruminant lactating mammary gland slices could use acetate for the synthesis of fat, provided that glucose was also added. Experiments in vivo laid emphasis upon the synthesis of short-chain fatty acids by the mammary gland. Popják & Beeckmans (1950) showed that injection of [ carboxy - 14 C]acetate into the pregnant rabbit gave rise to a high degree of labelling in the mammary gland fat. Fractionation of these fatty acids (Popják, Folley & French 1950) showed that the label was predominantly concentrated in the short-chain fatty acids, and that this labelling was far higher than that found in the liver fatty acids, indicating synthesis in the gland itself.


1982 ◽  
Vol 94 (2) ◽  
pp. 251-NP ◽  
Author(s):  
Janet M. Nolin ◽  
Betty J. Thompson ◽  
Stuart Smith

Two approaches were used to establish the intercellular distribution of fatty acid synthetase and thioesterase II in the lactating rat mammary gland. Thioesterase II is the chain-length regulatory enzyme in the biosynthesis of the medium-chain fatty acids characteristic of milk fat. Using immunohistochemical techniques, immunoreactive fatty acid synthetase was found in both mammary adipocytes and epithelial cells; in contrast, immunoreactive thioesterase II was confined to the epithelial cells. In metabolic studies, adipocytes and epithelial cells were isolated from lactating rat mammary glands after digestion with collagenase and thermolysin, and their lipogenic activity was studied using isotopically labelled acetate. Consistent with the immunohistochemical data, adipocytes synthesized exclusively long-chain fatty acids whereas epithelial cells synthesized predominantly medium-chain fatty acids. The results indicate that the capacity for synthesis of medium-chain fatty acids is a unique property of the epithelial cell component of the mammary gland.


1974 ◽  
Vol 142 (3) ◽  
pp. 611-618 ◽  
Author(s):  
D. Michael W. Salmon ◽  
Neil L. Bowen ◽  
Douglas A. Hems

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.


2010 ◽  
Vol 39 (10) ◽  
pp. 2297-2303 ◽  
Author(s):  
Daniele Cristina da Silva-Kazama ◽  
Geraldo Tadeu dos Santos ◽  
Paula Toshimi Matumoto Pintro ◽  
Jesuí Vergílio Visentainer ◽  
Ricardo Kazama ◽  
...  

Eight Holstein cows with body weight 570 ± 43 kg and 60 ± 20 lactation days were distributed in a double Latin square design with four 21-day periods to determine the effects of feeding ground or whole flaxseed with or without monensin supplementation (0.02% on a dry matter basis) on fatty acid profile of butter stored for 15 and 45 days. Ground flaxseed supply, in comparison to whole flaxseed, reduced relative percentages of 16:0, cis7-16:1, 17:0, and cis10-17:1 but it increased those of cis9,trans11-18:2, cis3-18:3, and omega 3 fatty acids in butter fat, reducing relative percentage of medium-chain fatty acids and increasing the content of polyunsaturated fatty acids. Supplementation with monensin increased relative percentages of cis9,trans11-18:2 and tended to increase relative percentage of 17:0 and decrease that of saturated fatty acids in butter. Butter from cows fed diet with monensin presented lower relative percentages of cis 6-20:4. Relative percentages of cis 9-16:1, cis10-17:1, 18:0, trans11-18:1, cis9-18:1, cis3-18:3, cis6-20:4 in butter stored for 15 days were higher than those stored for 45 days and the relative percentages of cis3-20:5 tended to decrease with the increase of storage period. As a result, relative percentages of saturated fatty acids and medium-chain fatty acids increased with storage time, while those of monounsaturated and long-chain fatty acids decreased. Butter enriched with polyunsaturated fatty acids may have a shorter shelf life due to the negative effect of storage on fatty acid profile which may cause oxidation and rancidity.


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