Dietary protein and amino acid restriction: Roles in metabolic health and aging-related diseases

Prior studies have reported that dietary protein dilution (DPD) or amino acid dilution promotes heightened water intake (i.e., hyperdipsia) however, the exact dietary requirements and the mechanism responsible for this effect are still unknown. Here, we show that dietary amino acid (AA) restriction is sufficient and required to drive hyperdipsia during DPD. Our studies demonstrate that particularly dietary essential AA (EAA) restriction, but not non-EAA, is responsible for the hyperdipsic effect of total dietary AA restriction (DAR). Additionally, by using diets with varying amounts of individual EAA under constant total AA supply, we demonstrate that restriction of threonine (Thr) or tryptophan (Trp) is mandatory and sufficient for the effects of DAR on hyperdipsia and that liver-derived fibroblast growth factor 21 (FGF21) is required for this hyperdipsic effect. Strikingly, artificially introducing Thr de novo biosynthesis in hepatocytes reversed hyperdipsia during DAR. In summary, our results show that the DPD effects on hyperdipsia are induced by the deprivation of Thr and Trp, and in turn, via liver/hepatocyte-derived FGF21.

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Comprehensive assessment of post-prandial protein handling by the application of intrinsically labelled protein in vivo in human subjects

Proceedings of The Nutrition Society ◽

10.1017/s0029665120008034 ◽

2021 ◽

pp. 1-9

Author(s):

Jorn Trommelen ◽

Andrew M. Holwerda ◽

Philippe J. M. Pinckaers ◽

Luc J. C. van Loon

Keyword(s):

Protein Synthesis ◽

Amino Acid ◽

Stable Isotope ◽

Dietary Protein ◽

Protein Metabolism ◽

Muscle Protein ◽

Human Subjects ◽

Whole Body ◽

Body Protein

All human tissues are in a constant state of remodelling, regulated by the balance between tissue protein synthesis and breakdown rates. It has been well-established that protein ingestion stimulates skeletal muscle and whole-body protein synthesis. Stable isotope-labelled amino acid methodologies are commonly applied to assess the various aspects of protein metabolism in vivo in human subjects. However, to achieve a more comprehensive assessment of post-prandial protein handling in vivo in human subjects, intravenous stable isotope-labelled amino acid infusions can be combined with the ingestion of intrinsically labelled protein and the collection of blood and muscle tissue samples. The combined application of ingesting intrinsically labelled protein with continuous intravenous stable isotope-labelled amino acid infusion allows the simultaneous assessment of protein digestion and amino acid absorption kinetics (e.g. release of dietary protein-derived amino acids into the circulation), whole-body protein metabolism (whole-body protein synthesis, breakdown and oxidation rates and net protein balance) and skeletal muscle metabolism (muscle protein fractional synthesis rates and dietary protein-derived amino acid incorporation into muscle protein). The purpose of this review is to provide an overview of the various aspects of post-prandial protein handling and metabolism with a focus on insights obtained from studies that have applied intrinsically labelled protein under a variety of conditions in different populations.

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Ileal amino acid digestibility of some novel dietary protein sources for growing chickens

Journal of the Science of Food and Agriculture ◽

10.1002/jsfa.2657 ◽

2006 ◽

Vol 86 (15) ◽

pp. 2603-2608 ◽

Cited By ~ 5

Author(s):

Velmurugu Ravindran ◽

Patrick CH Morel

Keyword(s):

Amino Acid ◽

Dietary Protein ◽

Protein Sources

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Dietary protein paradox: decrease of amino acid availability induced by high-protein diets

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1993.264.6.g1057 ◽

1993 ◽

Vol 264 (6) ◽

pp. G1057-G1065 ◽

Cited By ~ 11

Author(s):

C. Moundras ◽

C. Remesy ◽

C. Demigne

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Dietary Protein ◽

High Protein ◽

Glutamine Metabolism ◽

Metabolic Adaptation ◽

Casein Diet ◽

Serine Dehydratase ◽

High Protein Diets ◽

Protein Diets

The aim of the present study was to evaluate the effect of changes in dietary protein level on overall availability of amino acids for tissues. For this purpose, rats were adapted to diets containing various concentrations of casein (7.5, 15, 30, and 60%) and were sampled either during the postprandial or postabsorptive period. In rats fed the protein-deficient diet, glucogenic amino acids (except threonine) tended to accumulate in plasma, liver, and muscles. In rats fed high-protein diets, the hepatic balance of glucogenic amino acids was markedly enhanced and their liver concentrations were consistently depressed. This response was the result of a marked induction of amino acid catabolism (a 45-fold increase of liver threonine-serine dehydratase activity was observed with the 60% casein diet). The muscle concentrations of threonine, serine, and glycine underwent changes parallel to plasma and liver concentrations, and a significant reduction of glutamine was observed. During the postabsorptive period, adaptation to high-protein diets resulted in a sustained catabolism of most glucogenic amino acids, which accentuated the drop in their concentrations (especially threonine) in all the compartments studied. The time course of metabolic adaptation from a 60 to a 15% casein diet has also been investigated. Adaptation of alanine and glutamine metabolism was rapid, whereas that of threonine, serine, and glycine was delayed and required 7-11 days. This was paralleled by a relatively slow decay of liver threonine-serine dehydratase (T-SDH) activity in contrast to the rapid adaptation of pyruvate kinase activity after refeeding a high-carbohydrate diet.(ABSTRACT TRUNCATED AT 250 WORDS)

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The effect of feeding high levels of low-quality proteins to growing chickens

British Journal Of Nutrition ◽

10.1017/s0007114575000426 ◽

1975 ◽

Vol 34 (3) ◽

pp. 363-373 ◽

Cited By ~ 20

Author(s):

E. Wetnli ◽

T. R. Morris ◽

T. P. Shresta

Keyword(s):

Growth Rate ◽

Amino Acid ◽

Dietary Protein ◽

Soya Bean ◽

Maximum Efficiency ◽

Food Utilization ◽

The Third ◽

Bean Meal ◽

Groundnut Meal ◽

Soya Bean Meal

1. Three growth trials were done using male broiler chicks. In the first two trials, groundnut meal was used, with and without supplementary methionine and lysine. In the third trial, soya-bean meal was used with and without supplementary methionine. Protein levels ranged in the first trial from 120 to 420 g/kg diet and in the third trial from 120 to 300 g/kg diet. Thus the assumed minimal amino acid requirements of the chick were supplied by high levels of low-quality dietary protein.2. Diets based on cereals and groundnut meal did not support maximum live-weight gain or maximum efficiency of food utilization at any level of dietary protein. When the principal deficiencies of lysine and methionine were corrected, this protein mixture was capable of supporting the same growth rate as a control diet of cereals and herring meal.3. Diets based on maize and soya-bean meal did not support quite the same growth rate as similar diets supplemented with methionine, even though the protein level in the unsupplemented diets was sufficient to meet the assumed methionine requirements.4. These results are interpreted as examples of amino acid imbalance in diets composed of familiar feeding-stuffs. It is concluded that one cannot assume that the poor quality of a protein source can always be offset by increasing the concentration of dietary protein.

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Implications of amino acid sensing and dietary protein to the aging process

Experimental Gerontology ◽

10.1016/j.exger.2018.11.021 ◽

2019 ◽

Vol 115 ◽

pp. 69-78 ◽

Cited By ~ 11

Author(s):

Oleh Lushchak ◽

Olha M. Strilbytska ◽

Ihor Yurkevych ◽

Alexander M. Vaiserman ◽

Kenneth B. Storey

Keyword(s):

Amino Acid ◽

Dietary Protein ◽

Aging Process ◽

Amino Acid Sensing

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The effect of protein- and non-protein-nitrogen supplements to maize silage on total amino acid supply in young cattle

British Journal Of Nutrition ◽

10.1079/bjn19820138 ◽

1982 ◽

Vol 48 (3) ◽

pp. 527-541 ◽

Cited By ~ 37

Author(s):

B. R. Cottrill ◽

D. E. Beever ◽

A. R. Austin ◽

D. F. Osbourn

Keyword(s):

Amino Acids ◽

Small Intestine ◽

Amino Acid ◽

Dietary Protein ◽

Fish Meal ◽

Metabolizable Energy ◽

Low Energy ◽

Maize Silage ◽

Protein Nitrogen ◽

Microbial N

1. A total of six diets based on maize silage were formulated to examine the effect of protein- and non-protein-nitrogen, and energy supplementation on the flow of amino acids to the small intestine and the synthesis of microbial amino acids in the rumen of growing cattle. All diets contained 24 g totai nitrogen (N)/kg dry matter (DM), of which 550 g N/kg total N was supplied by either urea or fish meal. Four diets contained low levels of barley (estimated total dietary metabolizable energy content of 10·4 M J/kgDM) and urea-N and fish meal-N were supplied in the ratios 3:1, 1·4:1, 0·6:1 and 0·3:1. The other two diets contained between 300 and 400 g barley/kg total diet (11·3 MJ metabolizable energy/kg DM) and the urea-N to fish meal-N ratios were 3:1 and 0·3:1.2. On the four low-energy diets, fish meal inclusion tended to reduce the extent of organic matter (OM) digestion in the rumen but significantly increased duodenal amino acid supply (P< 0·05) in a quadratic manner. Microbial-N synthesis was increased by the two intermediate levels of fish meal supplementation but declined at the highest level of inclusion. With increasing levels of fish meal inclusion, a greater proportion of the dietary protein was found to escape rumen degradation and the apparent degradabilities of fish meal and maize-silage protein of all four diets were estimated to be 0·22 and 0·73 respectively.3. The substitution of barley for part of the maize silage enhanced duodenal supply of amino acids, irrespective of the form of the N supplement, and stimulated microbial amino acid synthesis. For all diets efficiency of microbial-N synthesis was found to vary between 22·5 and 46 g N/kg rumen-digested OM. Contrary to what was found for low-energy diets, the inclusion of fish meal tended to reduce the flow of dietary protein to the small intestine, but these differences were not statistically significant.4. The results appertaining to microbial synthesis, dietary protein degradabilities and duodenal amino acid flow for all diets are discussed in relation to the Agricultural Research Council (1980) proposals for the protein requirements of ruminants, and the production responses observed when similar diets were fed to growing cattle.

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Whole-body leucine and lysine metabolism: response to dietary protein intake in young men

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1981.240.6.e712 ◽

1981 ◽

Vol 240 (6) ◽

pp. E712-E721 ◽

Cited By ~ 17

Author(s):

K. J. Motil ◽

D. E. Matthews ◽

D. M. Bier ◽

J. F. Burke ◽

H. N. Munro ◽

...

Keyword(s):

Amino Acid ◽

Dietary Protein ◽

Protein Intake ◽

Whole Body ◽

Dietary Protein Intake ◽

Body Protein ◽

Fed State ◽

Amino Acid Requirements ◽

Maintenance Requirements ◽

Lysine Metabolism

Whole-body leucine and lysine metabolism was explored in young adult men by a primed constant intravenous infusion of a mixture of L-[1–13C]leucine and L-[alpha-15N]lysine over a 4-h period. Subjects were studied after an overnight fast (postabsorptive state) or while consuming hourly meals (fed state) after adaptation to diets providing either a surfeit level of protein (1.5 g.kg body-1.day-1), a level approximating maintenance requirements (marginal intake) (0.6 g.kg body wt-1.day-1), or a grossly inadequate level (0.1 g.kg-1.day-1). The change in protein intake from a marginal to a surfeit level was associated with an increased leucine flux and incorporation of leucine into body protein. In the fed state, oxidation of leucine increased sharply and release of leucine from tissue protein diminished. When dietary protein intake was reduced from the requirement to inadequate level, leucine flux and body protein synthesis and protein breakdown were reduced, together with a smaller reduction in leucine oxidation. The response of the metabolism of [15N]lysine was responsible for maintenance of leucine and other essential amino acid economy, and they appear to be related to the nitrogen and amino acid requirements of the subject. These findings also demonstrate an effect of meals, modulated by their protein content, on the dynamics of whole-body amino acid metabolism.

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