Mammary gland utilization of amino acids and energy metabolites differs when dairy cow rations are isoenergetically supplemented with protein and fat

The transition period of the dairy cow involves the end of pregnancy, parturition, and the onset of lactation. Multifaceted and rapid changes occur during this time, and in particular, the increase of milk secretion requires the large-scale reorientation of metabolism. The underlying mechanisms of this metabolic regulation are collectively named homeorhesis, a process that governs milk production during this phase and that exhibits (A) a chronic nature, (B) the simultaneous inclusion of multiple tissues, and (C) altered responses to homeostatic signals, but (D) no direct feedback mechanisms for possible control or limitation. Priority of milk production is one important consequence of this homeorhetic regulation with possible constraints on other physiological functions. These general properties of the homeorhetic regulation of milk secretion are specifically characterized by a) milk production according milking (suckling) frequency, b) a natural but inadequate dry matter intake, c) the mobilization of fat acids + glycerol from adipose tissue and of amino acids from protein, d) the partitioning of metabolites, IgG, and dietary nutrients to the mammary gland, e) the stimulation of milk production by high protein intake, and f) a negligible negative energy balance (NEB) at low milk production. Such a combination assures the optimal milk yield for the nutrition of the calf and for its successful survival but without a metabolic challenge or health risk for the cow. However, selection for higher milk production (uncoupled from calf nutrition) and management have changed the above-listed properties, and the regulation of homeorhetic milk production of the modern high-producing dairy cow is nowadays mostly characterized by a) increasing and maximal milk production at increased milking frequency and, under certain circumstances, the uncoupling of the GH-IGF-1 axis, b) enduring insufficient dry matter intake in relation to requirement, c) the mobilization of energy (lipolysis) and release of non-esterified fatty acids (NEFA) above the acute requirement, d) the mobilization of amino acids, e) the partitioning of metabolites, IgG, and dietary nutrient to the mammary gland, f) the potential enhanced partitioning of energy to the mammary gland at high CP intake, g) a sudden and long-lasting NEB, and h) possibly lower weight gain or even net loss of energy during the entire lactation period. These altered and often unfavorable characteristics of high milk production are, furthermore, still regulated by homeorhesis and are thus also given top priority, lack feedback control, and possibly ensue at the expense of other functions without regard for health risks. Hence, the promotion of milk yield by breeding or management might cause metabolic overload, imbalances, or even antagonisms and makes possible health hazards evident. The high incidence of various diseases, the untimely culling rates, and the increasing number of dead cows during early lactation support the assumption of general health threats at high milk production. For this reason, more attention should be paid to the physiological mechanisms of homeorhetic-regulated milk production, its indisputable alterations by breeding and management, and the resulting health risks.

Download Full-text

Gamma-Glutamyl-Amino Acids as Signals for the Hormonal Regulation of Amino Acid Uptake by the Mammary Gland of the Lactating Rat

Neonatology ◽

10.1159/000242178 ◽

1985 ◽

Vol 48 (4) ◽

pp. 250-256 ◽

Cited By ~ 8

Author(s):

Juan R. Viña ◽

Inmaculada R. Puertes ◽

Juan B. Montoro ◽

Guillermo T. Saez ◽

José Viña

Keyword(s):

Amino Acids ◽

Mammary Gland ◽

Amino Acid ◽

Hormonal Regulation ◽

Amino Acid Uptake ◽

Acid Uptake ◽

Gamma Glutamyl

Download Full-text

The effects of PBN (phenyl-butyl-nitrone) on GLT-1 levels and on the extracellular levels of amino acids and energy metabolites in a model of iron-induced posttraumatic epilepsy

Epilepsy Research ◽

10.1016/j.eplepsyres.2003.09.004 ◽

2003 ◽

Vol 56 (2-3) ◽

pp. 165-173 ◽

Cited By ~ 14

Author(s):

Carolina Samuelsson ◽

Eva Kumlien ◽

Åse Elfving ◽

Dan Lindholm ◽

Elisabeth Ronne-Engström

Keyword(s):

Amino Acids ◽

Posttraumatic Epilepsy ◽

Energy Metabolites

Download Full-text

Diets rich in starch improve the efficiency of amino acids use by the mammary gland in lactating Jersey cows

Journal of Dairy Science ◽

10.3168/jds.2015-9518 ◽

2015 ◽

Vol 98 (10) ◽

pp. 6939-6953 ◽

Cited By ~ 6

Author(s):

G. Cantalapiedra-Hijar ◽

I. Ortigues-Marty ◽

S. Lemosquet

Keyword(s):

Amino Acids ◽

Mammary Gland ◽

Jersey Cows

Download Full-text

Role of Prolactin, Growth Hormone and Insulin-Like Growth Factor 1 in Mammary Gland Involution in the Dairy Cow

Journal of Dairy Science ◽

10.3168/jds.s0022-0302(02)74102-7 ◽

2002 ◽

Vol 85 (3) ◽

pp. 507-513 ◽

Cited By ~ 61

Author(s):

P.A. Accorsi ◽

B. Pacioni ◽

C. Pezzi ◽

M. Forni ◽

D.J. Flint ◽

...

Keyword(s):

Growth Hormone ◽

Mammary Gland ◽

Growth Factor ◽

Dairy Cow ◽

Insulin Like Growth Factor ◽

Mammary Gland Involution

Download Full-text

Role of the gamma-glutamyl cycle in the regulation of amino acid translocation

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1989.257.6.e916 ◽

1989 ◽

Vol 257 (6) ◽

pp. E916-E922 ◽

Cited By ~ 5

Author(s):

J. R. Vina ◽

M. Palacin ◽

I. R. Puertes ◽

R. Hernandez ◽

J. Vina

Keyword(s):

Amino Acids ◽

Mammary Gland ◽

Amino Acid ◽

Amino Acid Transport ◽

Acid Transport ◽

Pregnant Rats ◽

Gamma Glutamyl ◽

Extracellular Signals ◽

Previously Treated

Amino acid translocation was studied in the mammary gland of lactating rats and in the placenta of pregnant rats. The uptake of amino acids by the mammary gland is maximal on days 10-14 of lactation and is minimal on days 19-21. However, on day 19 maximal uptake can be restored by injection of 1) small amounts of gamma-glutamyl amino acids, 2) 5-oxoproline, and 3) an inhibitor of 5-oxoprolinase. A severe decrease in uptake of amino acids at the peak of lactation is provoked by anthglutin, an inhibitor of gamma-glutamyltranspeptidase (GGT). Simultaneous injection of 5-oxoproline blocks these effects of anthglutin. In pregnant rats, inhibition (79%) of placental GGT activity by acivicin results in a 50% decrease of placental L-[U-14C]-alanine transfer and 70-80% decrease in its incorporation into the placental and fetal proteins. Infusion of 5-oxoproline to mothers previously treated with acivicin restored the L-[U-14C]-alanine transfer. Acivicin or 5-oxoproline did not modify the transfer and metabolism of D-[U14C]glucose by the fetal placental unit. These results show that the gamma-glutamyl cycle should not be considered a mechanism for amino acid transport but rather a generator of extracellular signals, gamma-glutamyl amino acids, that are converted intracellularly to 5-oxoproline, which activates uptake and/or metabolism of amino acids.

Download Full-text

Responses of the bovine mammary glands to absorptive supply of single amino acids

Canadian Journal of Animal Science ◽

10.4141/a02-077 ◽

2003 ◽

Vol 83 (3) ◽

pp. 341-355 ◽

Cited By ~ 31

Author(s):

J. P. Cant ◽

R. Berthiaume ◽

H. Lapierre ◽

P. H. Luimes ◽

B. W. McBride ◽

...

Keyword(s):

Amino Acids ◽

Blood Flow ◽

Amino Acid ◽

General Circulation ◽

Milk Protein ◽

Mammary Glands ◽

Protein Yield ◽

Yield Response ◽

Peripheral Tissues ◽

Energy Metabolites

In this review, we discuss the mechanismsof responses of various tissues of the lactating dairy cow, particularly the mammary glands, to perturbations in supply of single amino acids that result in observed milk protein yields. Additions of methionine, lysine, histidine or leucine to the absorptive supply cause arterial concentrations of these amino acids to increase, mammary extractions to drop and mammary blood flow to decrease. Single subtractions of essential amino acids have the opposite effect. Changes in mammary blood flow that have been recorded can be explained as attempts by the mammary glands to restore intracellular ATP balance in the face of altered concentrations of energy metabolites in the general circulation. In a quantitative sense, milk protein yield is relatively insensitive to fluctuations in arterial amino acid concentrations but can be stimulated by any one of a number of amino acids. In this context, it is suggested that the designation of a limiting amino acid is not appropriate to the purpose of predicting milk protein yield. Rather, milk protein synthesis appears to operate at a predetermined rate set by external communications of milk withdrawal rate, physiological state and overall nutritional status. Utilization of amino acids (AA) by splanchnic and peripheral tissues, in coordination with the mammary setpoint, offsets imperfections in the dietary AA supply. How strongly an individual AA influences the mammary setpoint, arterial concentrations of energy metabolites, and mammary AA transport capacity will determine the magnitude of the milk protein yield response when its absorptive supply is changed. Key words: Dairy cows, milk protein, amino acid

Download Full-text

Amino acid transportation, sensing and signal transduction in the mammary gland: key molecular signalling pathways in the regulation of milk synthesis

Nutrition Research Reviews ◽

10.1017/s0954422420000074 ◽

2020 ◽

Vol 33 (2) ◽

pp. 287-297

Author(s):

Zhihui Wu ◽

Jinghui Heng ◽

Min Tian ◽

Hanqing Song ◽

Fang Chen ◽

...

Keyword(s):

Amino Acids ◽

Mammary Gland ◽

Milk Protein ◽

Building Blocks ◽

Branched Chain Amino Acids ◽

Signalling Pathways ◽

Recent Advances ◽

Branched Chain ◽

Molecular Signalling Pathways

AbstractThe mammary gland, a unique exocrine organ, is responsible for milk synthesis in mammals. Neonatal growth and health are predominantly determined by quality and quantity of milk production. Amino acids are crucial maternal nutrients that are the building blocks for milk protein and are potential energy sources for neonates. Recent advances made regarding the mammary gland further demonstrate that some functional amino acids also regulate milk protein and fat synthesis through distinct intracellular and extracellular pathways. In the present study, we discuss recent advances in the role of amino acids (especially branched-chain amino acids, methionine, arginine and lysine) in the regulation of milk synthesis. The present review also addresses the crucial questions of how amino acids are transported, sensed and transduced in the mammary gland.

Download Full-text

Milk Protein Precursors in the Goat During Late Lactation

Proceedings of the British Society of Animal Production (1972) ◽

10.1017/s0308229600023321 ◽

1993 ◽

Vol 1993 ◽

pp. 1-1

Author(s):

B.J. Bequette ◽

F.R.C. Backwell ◽

A.G. Calder ◽

J.A. Metcalf ◽

D. Wray-Cahen ◽

...

Keyword(s):

Amino Acids ◽

Protein Synthesis ◽

Mammary Gland ◽

Milk Protein ◽

Protein S ◽

Dairy Goats ◽

Protein Precursor ◽

Previous Hypothesis ◽

Casein Protein ◽

Isotope Kinetics

Previously, we have reported on work in dairy goats using stable isotope kinetics to examine the precursors for milk protein synthesis (1). Contrary to a previous hypothesis (2), these results suggested that blood free amino acids (AA) are not simply transported into the mammary gland and incorporated directly into milk protein. Although the latter may still occur, a substantial amount of the AA for milk protein synthesis appears to be channelled through constitutive mammary gland protein(s) first. Moreover, the data indicated that a proportion (12-20%) of the casein protein precursor may be derived from extra-mammary sources other than blood free AA, e.g. peptides and/or proteins. It may be possible therefore to alter milk protein synthesis by the provision of different forms of precursor amino acids. Since the previous study was in goats during early lactation (day 61 ± 11), the present study reports on the precursors for milk protein synthesis in goats during late lactation, and allows a comparison between stages of lactation.

Download Full-text

Intermediary Metabolism in the Dairy Cow

Animal Science ◽

10.1017/s1357729805000019 ◽

2005 ◽

Vol 80 (1) ◽

pp. 1-1

Keyword(s):

Amino Acids ◽

Mammary Gland ◽

State Of The Art ◽

Intermediary Metabolism ◽

Model Construction ◽

British Society ◽

Efficiency Coefficient ◽

Animal Science ◽

Physiology And Biochemistry ◽

Simple Equations

Current feed evaluation systems for ruminants include very simple models of intermediary metabolism – either single, static coefficients or simple equations to describe the efficiency with which the energy and nitrogen available for absorption are converted into milk and meat. For example, the revised UK system ‘Feed into milk’ defines a fixed efficiency of utilization of metabolizable protein (MP) for milk production of 0·68 (Thomas, 2004). Such a simple ‘efficiency’ coefficient is the tip of the tip of a rather large iceberg, representing the metabolism of the end-products of digestion between the point of their absorption into the animal and their use for the synthesis of milk and meat. The complex biochemistry of metabolism in the tissues of the gut (the portal-drained viscera, PDV), the liver and other internal organs, the adipose tissue, muscle and mammary gland: all reduced (a term used nonpejoratively) to single coefficients or simple equations. Simple and very useful – up to a point.A Working Party established by the Agricultural and Food Research Council (AFRC) Technical Committee on Responses to Nutrients wrote, in 1998, ‘The present state of knowledge on the nutritional and hormonal interactions “in intermediary metabolism” is considerably inferior to the knowledge which exists with respect to the processes of ruminal and intestinal digestion, and thus to develop a satisfactory model of metabolism requires research not only in model construction but also in the physiology and biochemistry of animals.’ (AFRC, 1998). Perhaps contrary to the common perception of a contracting research base in farm animal science, the required research in physiology and biochemistry is continuing, research which is summarized and put in context by two review articles in this issue of Animal Science.Kristensen (2005) focuses on a key aspect of the ‘energy economy’ of the cow: the metabolism of volatile fatty acids (VFA) in the tissues of the digestive tract and the liver. Using novel techniques, Kristensen and colleagues have re-examined (and overturned?) one of the key paradigms of ruminant physiology, that a large proportion of the VFA generated by fermentation in the rumen is metabolised during absorption.Researchers from Canada and the UK are untangling factors affecting the partitioning of absorbed amino acids between use for protein synthesis and catabolism and this topic is reviewed by Lapierre et al. (2005). This paper emphasizes the important concept that ‘efficiency of utilization’ of absorbed amino acids is as much a function of demand (in the lactating cow, principally from the mammary gland) as it is of supply.The statement from AFRC (1998), quoted above, demands two activities, physiological research and model construction. These authors continue: ‘It is likely, however, that the best progress will be achieved if both types of research are undertaken in parallel.’ In a third review article in this volume, Hanigan (2005) summarizes the ‘state of the art’ in the simulation of PDV and hepatic metabolism, demonstrating how a computer model is a quantitative library in which to store new knowledge as well as a driver of future research.All three papers are based on presentations given to the 2004 annual meeting of the British Society of Animal Science. They demonstrate ‘the current state of the art’ for these important topics in ruminant physiology, offering a below the water-line look at these rather large and often forbidding icebergs. The reviews should serve as a valuable summary for those already working in this field of research, a concise and convenient introduction for those entering the field, and a window onto the future of practical systems for predicting the responses of dairy cows to the feedingstuffs they are offered.

Download Full-text