scholarly journals Fatty acid synthase is required for mammary gland development and milk production during lactation

2014 ◽  
Vol 306 (10) ◽  
pp. E1132-E1143 ◽  
Author(s):  
Janel Suburu ◽  
Lihong Shi ◽  
Jiansheng Wu ◽  
Shihua Wang ◽  
Michael Samuel ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Fatty Acid ◽  
Milk Production ◽  
Fatty Acid Synthesis ◽  
Fatty Acid Synthase ◽  
Mammary Gland Development ◽  
De Novo ◽  
Acid Synthesis ◽  
Lactating Mammary Gland ◽  
Gland Development

The mammary gland is one of the few adult tissues that strongly induce de novo fatty acid synthesis upon physiological stimulation, suggesting that fatty acid is important for milk production during lactation. The committed enzyme to perform this function is fatty acid synthase (FASN). To determine whether de novo fatty acid synthesis is obligatory or dietary fat is sufficient for mammary gland development and function during lactation, Fasn was specifically knocked out in mouse mammary epithelial cells. We found that deletion of Fasn hindered the development and induced the premature involution of the lactating mammary gland and significantly decreased medium- and long-chain fatty acids and total fatty acid contents in the milk. Consequently, pups nursing from Fasn knockout mothers experienced growth retardation and preweanling death, which was rescued by cross-fostering pups to a lactating wild-type mother. These results demonstrate that FASN is essential for the development, functional competence, and maintenance of the lactating mammary gland.

scholarly journals An intact SREBP1 pathway is essential for the t ‐10, c ‐12 CLA‐induced inhibition of de novo fatty acid synthesis in the murine lactating mammary gland

2009 ◽  
Vol 23 (S1) ◽  
Author(s):  
Monica R. Foote ◽  
Jenifer Monks ◽  
Kevin J. Harvatine ◽  
Margaret C. Neville ◽  
Yves R. Boisclair ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
De Novo ◽  
Acid Synthesis ◽  
Lactating Mammary Gland

scholarly journals Sterol regulatory element binding protein and dietary lipid regulation of fatty acid synthesis in the mammary epithelium

2010 ◽  
Vol 299 (6) ◽  
pp. E918-E927 ◽  
Author(s):  
Michael C. Rudolph ◽  
Jenifer Monks ◽  
Valerie Burns ◽  
Meridee Phistry ◽  
Russell Marians ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Mammary Gland ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
De Novo ◽  
Regulatory Element ◽  
Acid Synthesis ◽  
De Novo Lipogenesis ◽  
Mrna Levels ◽  
Sterol Regulatory Element

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.

scholarly journals Expression in Escherichia coli, purification and characterization of two mammalian thioesterases involved in fatty acid synthesis

1991 ◽  
Vol 273 (3) ◽  
pp. 787-790 ◽  
Author(s):  
J Naggert ◽  
A Witkowski ◽  
B Wessa ◽  
S Smith
Keyword(s):  
Escherichia Coli ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Fatty Acid Synthase ◽  
De Novo ◽  
Acid Synthesis ◽  
Temperature Sensitive ◽  
Lambda Repressor ◽  
Thioesterase Ii ◽  
Chain Lengths

Thioesterase I, a constituent domain of the multifunctional fatty acid synthase, and thioesterase II, an independent monofunctional protein, catalyse the chain-terminating reaction in fatty acid synthesis de novo at long and medium chain lengths respectively. The enzymes have been cloned and expressed in Escherichia coli under the control of the temperature-sensitive lambda repressor. The recombinant proteins are full-length catalytically competent thioesterases with specificities indistinguishable from those of the natural enzymes.

Mammary gland enzyme systems in the study of fatty-acid synthesis

1958 ◽  
Vol 149 (936) ◽  
pp. 414-420
Keyword(s):  
Fatty Acids ◽  
Mammary Gland ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Short Chain Fatty Acids ◽  
Acid Synthesis ◽  
Short Chain ◽  
Mammary Tissue ◽  
Lactating Mammary Gland ◽  
Chain Fatty Acids

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.

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