Metabolic regulation in the lactating mammary gland: a lipid synthesizing machine

2007 ◽  
Vol 28 (3) ◽  
pp. 323-336 ◽  
Author(s):  
Michael C. Rudolph ◽  
James L. McManaman ◽  
TzuLip Phang ◽  
Tanya Russell ◽  
Douglas J. Kominsky ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Microarray Analysis ◽  
Metabolic Regulation ◽  
Lipid Synthesis ◽  
Mammary Glands ◽  
Resonance Spectroscopy ◽  
Entire Body ◽  
Milk Lipid ◽  
Moderate Increase ◽  
Multiple Control

The mammary gland of the lactating mouse synthesizes and secretes milk lipid equivalent to its entire body weight in a single 20-day lactation cycle, making it one of the most active lipid synthetic organs known. We test the hypothesis that multiple control points and potential regulatory mechanisms regulate milk lipid synthesis at the level of gene expression. The mammary transcriptome of 130 genes involved in glucose metabolism was examined at late pregnancy and early lactation, utilizing data obtained from microarray analysis of mammary glands from quadruplicate FVB mice at pregnancy day 17 and lactation day 2. To correlate changes with physiological parameters, the metabolome obtained from magnetic resonance spectroscopy of flash-frozen glands at day 17 of pregnancy was compared with that at day 2 of lactation. A significant increase in carbohydrates (glucose, lactose, sialic acid) and amino acids (alanine, aspartate, arginine, glutamate) with a moderate increase in important osmolytes ( myo-inositol, betaine, choline derivatives) were observed in the lactating gland. In addition, diets containing 8% or 40% lipid were fed from lactation days 5–10 and mammary glands and livers of triplicate FVB mice prepared for microarray analysis. The results show that substantial regulation of lipid synthesis occurs at the level of mRNA expression and that some of the regulation points differ substantially from the liver. They also implicate the transcription factor SREBP-1c in regulation of part of the pathway.

scholarly journals Chain-length dependency of interactions of medium-chain fatty acids with glucose metabolism in acini isolated from lactating rat mammary glands. A putative feed-back to control milk lipid synthesis from glucose

1992 ◽  
Vol 281 (1) ◽  
pp. 273-278 ◽  
Author(s):  
K J Heesom ◽  
P F A Souza ◽  
V Ilic ◽  
D H Williamson
Keyword(s):  
Fatty Acids ◽  
Glucose Metabolism ◽  
Glucose Utilization ◽  
Lipid Synthesis ◽  
Mammary Glands ◽  
Milk Lipid ◽  
Medium Chain ◽  
Medium Chain Fatty Acids ◽  
Control Milk ◽  
Chain Fatty Acids

The effects of a series of medium-chain fatty acids (C6-C12) on glucose metabolism in isolated acini from lactating rat mammary glands have been studied. Hexanoate (C6) octanoate (C8) and decanoate (C10), but not laurate (C12), decreased [1-14C]glucose conversion into [14C]lipid and the production of 14CO2 (an index of the pentose phosphate pathway). With hexanoate and octanoate, glucose utilization was decreased, whereas decanoate had a slight stimulatory effect on glucose utilization, but there was a large accumulation of lactate. Addition of dichloroacetate (an inhibitor of pyruvate dehydrogenase kinase) decreased this accumulation of lactate and stimulated the conversion of [1-14C]glucose into [14C]lipid and 14CO2. Insulin had no effect on the rate of glucose utilization in the presence of hexanoate. It stimulated the rate in the presence of octanoate and laurate and increased the conversion of [1-14C]glucose into [14C]lipid in the presence of octanoate, decanoate or laurate. The major fate of 1-14C-labelled medium-chain fatty acids (C6, C8 and C12) was conversion into [14C]lipid. The proportion converted into 14CO2 decreased with increasing chain length, whereas the rate of [14C]lipid formation increased. It is concluded that the interactions between medium-chain fatty acids and glucose metabolism represent a feed-back mechanism to control milk lipid synthesis, and this may be important when milk accumulates in the gland.

Metabolism of leucine by the isolated perfused goat udder

1983 ◽  
Vol 50 (4) ◽  
pp. 413-424 ◽  
Author(s):  
Eddy Roets ◽  
Anne-Marie Massart-Leën ◽  
Georges Peeters ◽  
Roger Verbeke
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Mammary Gland ◽  
Milk Protein ◽  
Lipid Synthesis ◽  
Mammary Glands ◽  
Plasma Leucine ◽  
Free Plasma ◽  
Casein Synthesis

SUMMARYSeven lactating goat mammary glands from 6 goats were perfused for several hours in the presence of [U-14C]L-leucine (4 experiments) or [2-3H; l-14C]DL-leucine (3 experiments) and received adequate quantities of glucose, acetate and amino acids. Radioactivity in casein was mainly recovered in leucine and 90% of casein leucine was derived from free plasma leucine. About 64% of the leucine molecules were used for casein synthesis. Up to 12% of the molecules were channelled into lipid synthesis, while the remaining (up to 24%) were metabolized to CO2. From the 3H/14C ratio of casein and casein leucine, it was calculated that 70–80% of the leucine molecules were reversibly transaminated before their incorporation into milk protein. However, only 4–8% of the plasma leucine molecules were transaminated during passage through the udder. Different pools for oxidation and for protein synthesis may be present in the goat mammary gland.

scholarly journals The effects of cell death-inducing DNA fragmentation factor-α-like effector C (CIDEC) on milk lipid synthesis in mammary glands of dairy cows

2017 ◽  
Vol 100 (5) ◽  
pp. 4014-4024 ◽  
Author(s):  
Yang Yang ◽  
Ye Lin ◽  
Xiaoyu Duan ◽  
He Lv ◽  
Weinan Xing ◽  
...  
Keyword(s):  
Cell Death ◽  
Dairy Cows ◽  
Dna Fragmentation ◽  
Lipid Synthesis ◽  
Mammary Glands ◽  
Milk Lipid ◽  
Factor Α

scholarly journals Taurine reprograms mammary-gland metabolism and alleviates inflammation induced by Streptococcus uberis

2021 ◽  
Author(s):  
Riguo Lan ◽  
Zhixin Wan ◽  
Yuanyuan Xu ◽  
Zhenglei Wang ◽  
Shaodong Fu ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Metabolic Regulation ◽  
Inflammatory Responses ◽  
Mammary Epithelial Cells ◽  
Mammary Glands ◽  
Mammary Epithelial ◽  
Economic Losses ◽  
Intracellular Bacteria ◽  
Metabolic Dysfunction ◽  
Streptococcus Uberis

Abstract Streptococcus uberis (S. uberis) is an important pathogen causing mastitis,which causes continuous inflammation and dysfunction of mammary glands and leads to enormous economic losses. Most research on infection continues to be microbial metabolism-centric, and many overlook the fact that pathogens require energy from host. In this perspective, we uncover metabolic reprogramming during host immune responses is associated with infection-driven inflammation, particularly when caused by intracellular bacteria. Taurine, a metabolic regulator, has been shown to effectively ameliorate metabolic diseases. We evaluated the role of taurine in the metabolic regulation of S. uberis-induced mastitis. Metabolic profiling indicates that S. uberis exposure triggers inflammation and metabolic dysfunction of msmmary glands and mammary epithelial cells (MECs, the main functional cells in mammary glands). Challenge with S. uberis upregulates glycolysis and oxidative phosphorylation in MECs. Pretreatment with taurine restores metabolic homeostasis, reverses metabolic dysfunction by decrease of lipid, amino acid and especially energy disturbance in the infectious context, and alleviates excessive inflammatory responses. These outcomes depend on taurine-mediated activation of the AMPK–mTOR pathway, which inhibits the over activation of inflammatory responses and alleviates cellular damage. Thus, metabolic homeostasis is essential for reducing inflammation. Metabolic modulation can be used as a prophylactic strategy against mastitis. IMPORTANCE: Mastitis, especially caused by Streptococcus uberis, induces continuous inflammation and dysfunction of mammary glands, leading to enormous economic losses in dairy industry. Mammary epithelial cells (MECs) are mammary gland-resident major functional cells which occupy a significant role in maintaining homeostasis in mammary glands. MECs can adopt an inflammatory trending in response to S. uberis infection and try to clear these intracellular bacteria. Researchers at Nanjing Agricultural University in China found that S. uberis induces MECs acute inflammation caused by metabolic dysregulation, that is, increased oxidative phosphorylation (OXPHOS) and glycolysis. However, taurine pretreatment can enhance metabolic fitness and anti-inflammatory activity. As a potential therapy, metabolic regulation with taurine restored MECs homeostasis and reduced excessive inflammation. The findings suggest that modulating MECS metabolism might be a new therapeutic strategy for mastitis as well as other bacterial infections.

The effect of bromocriptine on mammary-gland ultrastructure of hyperprolactinemic rats

1984 ◽  
Vol 42 ◽  
pp. 204-205
Author(s):  
I.C. Murray
Keyword(s):  
Mammary Gland ◽  
Dopamine Agonist ◽  
Alveolar Epithelium ◽  
Mammary Glands ◽  
Female Rats ◽  
Control Group ◽  
Cell Hyperplasia ◽  
Once Daily ◽  
Long Evans

In women, hyperprolactinemia is often due to a prolactin (PRL)-secreting adenoma or PRL cell hyperplasia. RRL excess stimulates the mammary glands and causes proliferation of the alveolar epithelium. Bromocriptine, a dopamine agonist, inhibits PRL secretion and is given to women to treat nonpuerperal galactorrhea. Old female rats have been reported to have PRL cell hyperplasia or adenoma leading to PRL hypersecretion and breast stimulation. Herein, we describe the effect of bromocriptine and consequently the reduction in serum PRL levels on the ultrastructure of rat mammary glands.Female Long-Evans rats, 23 months of age, were divided into control and bromocriptine-treated groups. The control animals were injected subcutaneously once daily with a 10% ethanol vehicle and were later divided into a normoprolactinemic control group with serum PRL levels under 30 ng/ml and a hyperprolactinemic control group with serum PRL levels above 30 ng/ml.

INTERACTIONS OF OESTRONE AND TESTOSTERONE ON MAMMARY GLANDS OF MALE RABBITS

1961 ◽  
Vol 36 (1) ◽  
pp. 141-156 ◽  
Author(s):  
B. Bengtsson ◽  
A. Norgren
Keyword(s):  
Mammary Gland ◽  
Testosterone Propionate ◽  
Mammary Glands ◽  
List Type ◽  
Stunted Growth ◽  
Abnormal Growth ◽  
Growth Reaction ◽  
Extensive Growth ◽  
Higher Doses

ABSTRACT The effect of testosterone and oestrone on the mammary glands of castrated male rabbits was studied. Testosterone propionate was used in daily doses from 0.5 to 80 mg. The doses of oestrone ranged from 0.05 to 25 μg per day. Mammary glands were examined after 14, 28 or 56 days of injections. 1) Testosterone in doses below 20 mg failed to affect the mammary glands. With 40 or 80 mg a distinct, though abnormal growth reaction was consistently obtained. 2) Oestrone in doses lower than 0.5 μg did not stimulate mammary growth. With 0.5 μg and higher doses extensive growth of the mammary glands occurred. Stunted growth and secretion were found in the mammary glands of rabbits injected with 12.5 or 25 μg oestrone. 3) Testosterone in doses of 1 or 5 to 10 mg depressed or abolished the response of the mammary glands to 0.5 μg oestrone. When testosterone, in doses ineffective when given alone, was added to at least 3.125 μg oestrone, the mammary glands developed alveoli. The abnormalities produced by the highest doses of oestrone studied were exaggerated by the addition of testosterone. 4) The observations indicate a complicated interplay between the actions of testosterone and oestrone on the mammary gland of the rabbit. The interactions between testosterone and oestrone are presumably different from those observed between progesterone and oestrone.

EFFECT OF LOCALLY IMPLANTED OESTROGEN ON THE RESPONSE OF THE RAT'S LACTATING MAMMARY GLAND TO OXYTOCIN

1973 ◽  
Vol 73 (4) ◽  
pp. 700-712 ◽  
Author(s):  
J. D. Bruce ◽  
X. Cofre ◽  
V. D. Ramirez
Keyword(s):  
Mammary Gland ◽  
Mammary Glands ◽  
Myoepithelial Cells ◽  
Recording System ◽  
Saline Infusion ◽  
High Dose ◽  
Low Doses ◽  
Milk Ejection ◽  
Lactating Mammary Gland ◽  
Small Rise

ABSTRACT On the day following delivery (day 1 of lactation) one abdominal mammary gland was implanted with oestrogen and the contralateral gland received an empty needle. At 2, 5 or 10 days of lactation the rats were anaesthetized with pentobarbital and the nipples of both abdominal glands were cannulated and their pressures recorded by means of transducers coupled to an amplifier and recording system. The normal mammary glands of 5-day lactating rats responded to very low doses of oxytocin (Syntocinon®, Sandoz) (5× 10−8 mU) with a rhythmic elevation in pressure. However, saline infusion also evoked a small rise in intra-mammary pressure. Earlier (2 days) and later (10 days) in lactation the responses were smaller. Oestrogen decreases significantly the milk ejection response to oxytocin, and the effect was maximal at day 10 of lactation. Histological observations confirmed the diminished reaction of the gland to oxytocin, since the milk was retained in the alveoli of rats bearing a mammary-oestrogen implant. A paradoxical rise in pressure was detected in normal as well as in oestrogen-implanted glands when the lowest dose of oxytocin was injected in lactating rats which had previously received a high dose of oxytocin (50 mU or 500 mU). These results reinforce the hypothesis that oestrogen alters the milk ejection response to oxytocin and that the mechanism is probably related to changes in the contractility of the myoepithelial cells.

scholarly journals Regulation of lipogenic capacity in lactating rats

1982 ◽  
Vol 208 (3) ◽  
pp. 611-618 ◽  
Author(s):  
M R Grigor ◽  
A Geursen ◽  
M J Sneyd ◽  
S M Warren
Keyword(s):  
Mammary Gland ◽  
Fatty Acid ◽  
Malic Enzyme ◽  
Fatty Acid Synthase ◽  
Specific Activity ◽  
Mammary Glands ◽  
Lipogenic Enzymes ◽  
Pregnancy And Lactation ◽  
Specific Activities

1. The rate of mammary-gland lipogenesis measured in vivo from 3H2O was suppressed after decreasing the milk demand by decreasing the number of pups from ten to two or three, as well as by giving diets containing lipid [Grigor & Warren (1980) Biochem. J. 188, 61-65]. 2. The specific activities of the lipogenic enzymes fatty acid synthase, glucose 6-phosphate dehydrogenase and ‘malic’ enzyme increased between 6- and 10-fold in the mammary gland and between 2- and 3-fold in the livers during the first 10 days of lactation. The increases in specific activity coupled with the doubling of liver mass which occurred during pregnancy and lactation resulted in considerable differences in total liver activities when compared with virgin animals. 3. Although consumption of a diet containing 20% peanut oil suppressed the activities of the three lipogenic enzymes in the livers, only the ‘malic’ enzyme was affected in the mammary glands. 4. In contrast, decreased milk demand did not affect the specific activities of any of the liver enzymes, whereas it resulted in suppression of all three lipogenic enzymes of the mammary glands. There was no effect on either the cytoplasmic malate dehydrogenase or the lactate dehydrogenase of the mammary gland. 5. In all the experiments performed, the activity of the fatty acid synthase correlated with the amount of material precipitated by the rabbit antibody raised against rat fatty acid synthase.

Oxygen concentration in milk of healthy and mastitic cows and implications of low oxygen tension for the killing ofStaphylococcus aureusby bovine neutrophils

1988 ◽  
Vol 55 (4) ◽  
pp. 513-519 ◽  
Author(s):  
Susan J. Mayer ◽  
Avril E. Waterman ◽  
Peter M. Keen ◽  
Neil Craven ◽  
F. John Bourne
Keyword(s):  
Staphylococcus Aureus ◽  
Mammary Gland ◽  
Partial Pressure ◽  
Oxygen Concentration ◽  
Bactericidal Activity ◽  
Mammary Glands ◽  
Low Oxygen ◽  
Low Oxygen Tension ◽  
Bovine Neutrophils ◽  
Venous Plasma

SummaryThe partial pressure of O2in milk from normal cows and from cows with mastitis was measured and the concentrations of O2calculated. Oxygen levels of milk from normal cows were similar to those in venous plasma, but inflammation of the mammary gland led to a dramatic drop in O2concentration to < 10% of control values. Intracellular survival ofStaphylococcus aureusstrain M60 in bovine neutrophils was greater under anaerobic than aerobic conditions. The implications of low O2concentrations in milk from infected mammary glands for the bactericidal activity of bovine neutrophils is discussed.

The life and work of Dermot Hedley (‘Derek’) Williamson (1929–1998)

2001 ◽  
Vol 29 (2) ◽  
pp. 237-240
Author(s):  
R. D. Evans ◽  
M. Stubbs ◽  
G. F. Gibbons ◽  
E. A. Newsholme
Keyword(s):  
Metabolic Pathways ◽  
Metabolic Regulation ◽  
Ketone Body ◽  
Scientific Discovery ◽  
Lipid Synthesis ◽  
Acid Oxidation ◽  
Citation Classic ◽  
Integrated Regulation ◽  
Ketone Body Metabolism

Derek Williamson's scientific career spanned the ‘Golden Age’ of research into metabolic regulation, to which he made an important and sustained contribution. Derek joined Hans Krebs' laboratory at Sheffield University in 1946 and moved to Krebs' MRC Unit in Oxford in 1960. He elaborated an enzymic method for the determination of acetoacetate and 3-hydroxybutyrate [Williamson, Mellanby and Krebs, Biochem. J. (1962) 82, 90–96], which opened up the field of ketone body metabolism and its regulation and became a Citation Classic. Another Citation Classic followed [Williamson, Lund and Krebs, Biochem. J. (1967) 103, 514–527]. He moved with Krebs to the Metabolic Research Laboratory at the Radcliffe Infirmary in 1967, where he blossomed, formulating his ideas about the integrated regulation of metabolic pathways, particularly with regard to fatty acid oxidation, lipid synthesis and ketone body metabolism. His success was illustrated by more than 200 publications. Derek implanted and nurtured a sense of the excitement of scientific discovery in his colleagues and students, and he worked hard to provide a friendly, supportive and encouraging environment. Many lives have been enriched by the privilege of working with him.

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