scholarly journals Interactions between Growth of Muscle and Stature: Mechanisms Involved and Their Nutritional Sensitivity to Dietary Protein: The Protein-Stat Revisited

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 729
Author(s):  
D Joe Millward
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Dietary Protein ◽  
Protein Turnover ◽  
Protein Intake ◽  
Growth Regulation ◽  
Muscle Growth ◽  
Male Rats ◽  
Cellular Mechanisms ◽  
Bone Length

Childhood growth and its sensitivity to dietary protein is reviewed within a Protein-Stat model of growth regulation. The coordination of growth of muscle and stature is a combination of genetic programming, and of two-way mechanical interactions involving the mechanotransduction of muscle growth through stretching by bone length growth, the core Protein-Stat feature, and the strengthening of bone through muscle contraction via the mechanostat. Thus, growth in bone length is the initiating event and this is always observed. Endocrine and cellular mechanisms of growth in stature are reviewed in terms of the growth hormone-insulin like growth factor-1 (GH-IGF-1) and thyroid axes and the sex hormones, which together mediate endochondral ossification in the growth plate and bone lengthening. Cellular mechanisms of muscle growth during development are then reviewed identifying (a) the difficulties posed by the need to maintain its ultrastructure during myofibre hypertrophy within the extracellular matrix and the concept of muscle as concentric “bags” allowing growth to be conceived as bag enlargement and filling, (b) the cellular and molecular mechanisms involved in the mechanotransduction of satellite and mesenchymal stromal cells, to enable both connective tissue remodelling and provision of new myonuclei to aid myofibre hypertrophy and (c) the implications of myofibre hypertrophy for protein turnover within the myonuclear domain. Experimental data from rodent and avian animal models illustrate likely changes in DNA domain size and protein turnover during developmental and stretch-induced muscle growth and between different muscle fibre types. Growth of muscle in male rats during adulthood suggests that “bag enlargement” is achieved mainly through the action of mesenchymal stromal cells. Current understanding of the nutritional regulation of protein deposition in muscle, deriving from experimental studies in animals and human adults, is reviewed, identifying regulation by amino acids, insulin and myofibre volume changes acting to increase both ribosomal capacity and efficiency of muscle protein synthesis via the mechanistic target of rapamycin complex 1 (mTORC1) and the phenomenon of a “bag-full” inhibitory signal has been identified in human skeletal muscle. The final section deals with the nutritional sensitivity of growth of muscle and stature to dietary protein in children. Growth in length/height as a function of dietary protein intake is described in the context of the breastfed child as the normative growth model, and the “Early Protein Hypothesis” linking high protein intakes in infancy to later adiposity. The extensive paediatric studies on serum IGF-1 and child growth are reviewed but their clinical relevance is of limited value for understanding growth regulation; a role in energy metabolism and homeostasis, acting with insulin to mediate adiposity, is probably more important. Information on the influence of dietary protein on muscle mass per se as opposed to lean body mass is limited but suggests that increased protein intake in children is unable to promote muscle growth in excess of that linked to genotypic growth in length/height. One possible exception is milk protein intake, which cohort and cross-cultural studies suggest can increase height and associated muscle growth, although such effects have yet to be demonstrated by randomised controlled trials.

Dietary protein requirements and body protein metabolism in endurance-trained men

1989 ◽  
Vol 66 (6) ◽  
pp. 2850-2856 ◽  
Author(s):  
C. N. Meredith ◽  
M. J. Zackin ◽  
W. R. Frontera ◽  
W. J. Evans
Keyword(s):  
Dietary Protein ◽  
Protein Turnover ◽  
Protein Intake ◽  
Whole Body ◽  
Middle Aged ◽  
Body Protein ◽  
Protein Requirements ◽  
High Quality Protein ◽  
Effect Of Age ◽  
Lower Physical Activity

The effects of regular submaximal exercise on dietary protein requirements, whole body protein turnover, and urinary 3-methylhistidine were determined in six young (26.8 +/- 1.2 yr) and six middle-aged (52.0 +/- 1.9 yr) endurance-trained men. They consumed 0.6, 0.9, or 1.2 g.kg-1.day-1 of high-quality protein over three separate 10-day periods, while maintaining training and constant body weight. Nitrogen measurements in diet, urine, and stool and estimated sweat and miscellaneous nitrogen losses showed that they were all in negative nitrogen balance at a protein intake of 0.6 g.kg-1.day-1. The estimated protein requirement was 0.94 +/- 0.05 g.kg-1.day-1 for the 12 men, with no effect of age. Whole body protein turnover, using [15N]glycine as a tracer, and 3-methylhistidine excretion were not different in the two groups, despite lower physical activity of the middle-aged men. Protein intake affected whole body protein flux and synthesis but not 3-methylhistidine excretion. These data show that habitual endurance exercise was associated with dietary protein needs greater than the current Recommended Dietary Allowance of 0.8 g.kg-1.day-1. However, whole body protein turnover and 3-methylhistidine excretion were not different from values reported for sedentary men.

Telmisartan impairs the in vitro osteogenic differentiation of mesenchymal stromal cells from spontaneously hypertensive male rats

2021 ◽  
pp. 174609
Author(s):  
Victor Gustavo Balera Brito ◽  
Mariana Sousa Patrocinio ◽  
Ayná Emanuelli Alves Barreto ◽  
Sabrina Cruz Tfaile Frasnelli ◽  
Vanessa Soares Lara ◽  
...  
Keyword(s):  
Osteogenic Differentiation ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Male Rats ◽  
Spontaneously Hypertensive

Influence of Dietary Protein Intake on Whole-Body Protein Turnover in Humans

Diabetes Care ◽  
1991 ◽  
Vol 14 (12) ◽  
pp. 1189-1198 ◽  
Author(s):  
P. J. Garlick ◽  
M. A. McNurlan ◽  
P. E. Ballmer
Keyword(s):  
Dietary Protein ◽  
Protein Turnover ◽  
Protein Intake ◽  
Whole Body ◽  
Dietary Protein Intake ◽  
Body Protein

Dietary Protein and the Regulation of Long-Bone and Muscle Growth in the Rat

1994 ◽  
Vol 87 (2) ◽  
pp. 213-224 ◽  
Author(s):  
Z. A. H. Yayha ◽  
D. Joe Millward
Keyword(s):  
Growth Inhibition ◽  
Dietary Protein ◽  
Bone Growth ◽  
Muscle Growth ◽  
Protein Diet ◽  
Epiphyseal Cartilage ◽  
Muscle Weight ◽  
Tibial Length ◽  
Bone Length ◽  
Weight Growth

1. We report here studies of the interrelationship of bone and muscle growth in the rat and the regulatory role of dietary protein. Two experiments were undertaken. In experiment 1, growth inhibition was induced by ad libitum feeding of low protein diets containing 7%, 3.5% or 0.5% protein, with a control group fed a 20% protein diet. Measurements were made at 1, 3 and 7 days. In experiment 2, complete growth inhibition was induced by ad libitum feeding of a 0.5% protein diet with measurements at 7, 14 and 21 days followed by refeeding diets of 3%, 6%, 9%, 12% and 20% protein, with measurements after 3, 7, 10 and 14 days of refeeding (experimental days 24, 28, 31 and 35). Controls fed a 20% protein diet were studied at 0, 14, 21, 24, 28, 31 and 35 days. 2. Body weight growth stopped immediately in all reduced protein groups, with subsequent weight maintenance on the 7% protein diet, slight loss on the 3.5% protein diet or marked weight loss on the 0.5% protein diet, although food intake was maintained for 3 days, falling in all groups after this time. Inhibition of muscle growth was delayed in the 7% and 3.5% protein fed groups, with 12–15% increases in muscle weight after 7 days, but prompt growth inhibition occurred with the 0.5% protein diet with subsequent weight loss. In animals fed the control 20% protein diet, muscle weight (W) reflected tibial length (L) as W = L3.85/102.93 (r = 0.98, n = 98). Calculation of the muscle weight/bone length ratio (μg/mm3.85) indicated that a significant muscle deficit was apparent on day 3 and subsequently in the 0.5% protein fed rats, but not until day 7 in the 3.5% and 7% protein fed animals. 3. Total tibial length, epiphysis length and epiphyseal cartilage width were measured radiographically. In all groups there was no significant reduction in bone length growth during the first 3 days. After 3 days there were graded reductions on reduced protein intakes with complete inhibition on the 0.5% protein diet. Epiphyseal cartilage width responded sensitively, with a reduction within 24 h of the 0.5% and the 3.5% protein diets, and within 3 days of the 7% protein diet. The epiphysis length was only minimally affected. 4. In experiment 2, food intake increased immediately on refeeding in all except the 3% protein fed group. Accelerated body weight growth occurred in the 20%, 12% and 9% protein fed groups, slower growth in the 6% protein fed and little growth in the 3% protein fed group. Muscle growth commenced immediately in all groups, continuing at an accelerated rate in the 20%, 12% and 9% protein fed groups, at a slower but substantial rate in the 6% fed group and with little further growth in the 3% fed group. This allowed muscle repletion in relation to tibial length (i.e. μg/mm3.85) by day 7 in 9%, 12% and 20% fed protein groups. 5. Bone growth recovered slowly on refeeding, in a graded manner with the protein intakes. Significant increases in tibial length were only observed after 7 days of refeeding with 7–10 days required to fully restore growth in the 20% protein fed group and 10–14 days for the 12% and 9% protein fed groups. Only 50% of the age control rate was achieved in the 6% protein fed group, with little growth in the 3% protein fed group. Although gradual restoration of the epiphyseal cartilage width occurred in a graded manner with increasing protein intakes, complete restoration did not occur in any group. The small reduction in epiphysis length was partially, although not entirely, reversed by refeeding. 6. These studies demonstrate an anabolic drive of dietary protein on bone growth which responds in a graded manner to protein intake at levels in excess of those necessary for maximal rates of muscle growth. Muscle growth appears to be dependent in part on bone length growth, possibly through the anabolic influence of passive muscle stretch.

scholarly journals Effects of long-term protein excess or deficiency on whole-body protein turnover in sheep nourished by intragastric infusion of nutrients

1995 ◽  
Vol 73 (6) ◽  
pp. 829-839 ◽  
Author(s):  
S. M. Liu ◽  
G. E. Lobley ◽  
N. A. Macleod ◽  
D. J. Kyle ◽  
X.B. Chen ◽  
...  
Keyword(s):  
Dietary Protein ◽  
Protein Turnover ◽  
Protein Intake ◽  
Volatile Fatty Acids ◽  
Whole Body ◽  
N Losses ◽  
Body Protein ◽  
Fractional Rate ◽  
The Difference

The effect of long-term dietary protein excess and deficit on whole-body protein-N turnover (WBPNT) was examined in lambs nourished by intragastric infusions of nutrients. Ten sheep were given 500 mg N/kg metabolic weight (W0.75) per d from casein for 2 weeks and then either 50 (L), 500 (M) or 1500 (H) mg N/kgW0.75per d for 6 weeks. Volatile fatty acids were infused at 500 kJ/kgW0.75per d. Daily WBPNT was measured by continuous intravenous infusion of [l-13C]leucine 3 d before, and on days 2, 21 and 42 after the alteration in protein intake. Whole-body protein-N synthesis (WBPNS) was calculated as the difference between WBPNT and the protein-N losses as urinary NH3and urea. Whole-body protein-N degradation (WBPNS) was then estimated from WBPNS minus protein gain determined from N balance. Fractional rates of WBPNS and WBPND were calculated against fleece-free body N content. WBPNS rates at the L, M and H intakes were respectively 35·1, 41·5 amd 6·37 g/d (P< 0.001) on average over the 6 weeks and WBPND rates were 39·5, 41·1 and 56·8 g/d (P< 0.001). The fractional rates of WBPNS were 5·01, 6·37 and 7·73% per d (P< 0.001) while those of WBPND were 5·64, 6·29 and 6·81% per d (P< 0.005) respectively. On days 2, 21 and 42, WBPNS rates at intake H were 54·0, 61·8 and 75·4 g/d (P= 0·03) respectively, and WBPND rates were 43·2, 56·4 and 70·9 g/d (P= 0.03); at intake L the amounts were 38·2, 34·2 and 32·8 g/d for WBPNS (P= 0.003) and for WBPND were 43·4, 38·0 and 36·9 g/d (P= 0·016) respectively. There were no significant (P> 0·05) differences in fractional rates of WBPNS and WBPND with time at either the L or H intake. We concluded that absolute protein turnover was affected both by dietary protein intake and by body condition while the fractional rate of turnover was predominantly influenced by intake.

scholarly journals Ameliorative Effect of Mesenchymal Stromal Cells on Diabetic Nephropathy in Male Rats

2017 ◽  
Vol 45 (2) ◽  
pp. 125-133
Author(s):  
Ahmed Mansour ◽  
Hussein El-belbasi ◽  
Hamad El-saadawy ◽  
Engy Yassin
Keyword(s):  
Diabetic Nephropathy ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Male Rats ◽  
Ameliorative Effect

scholarly journals The effect of high salt and high protein intake on calcium metabolism, bone composition and bone resorption in the rat

2000 ◽  
Vol 84 (1) ◽  
pp. 49-56 ◽  
Author(s):  
Annette Creedon ◽  
Kevin D. Cashman
Keyword(s):  
Bone Resorption ◽  
Dietary Protein ◽  
Protein Intake ◽  
Fold Increase ◽  
Male Rats ◽  
Dietary Salt ◽  
Short Term ◽  
Bone Composition ◽  
Dietary Casein ◽  
High Dietary Protein

The effects of salt (NaCl) supplementation of rat diets (50 g/kg diet), with normal (200 g/kg) or high (500 g/kg) dietary casein content, were studied in 3-week-old male rats over a 3-week period. Weight gain was reduced by dietary salt but was unaffected by dietary casein. Salt-supplemented rats exhibited a two-and three-fold increase in urinary Mg and Ca excretion respectively, irrespective of dietary casein content. Dietary casein had no effect on urinary Ca or Mg. Salt reduced femoral mass but not femoral mass expressed relative to body weight, but neither variable was affected by dietary casein. Femoral Mg and P contents and concentrations were unaffected by dietary salt or casein. While femoral Ca concentration was unaffected by dietary salt, the Ca content was reduced by salt supplementation, irrespective of dietary casein content. Neither the content nor concentration of Ca in femora was affected by dietary casein. Urinary pyridinoline and deoxypyridinoline levels were increased by salt supplementation, irrespective of dietary casein content, but were unaffected by casein. Net Ca absorption was unaffected by dietary salt or casein. In conclusion, these results show that salt supplementation over the short-term increased the rate of bone resorption in rats. This was as a consequence of Na-induced calciuria. On the other hand, a high dietary protein intake had no effect on Ca metabolism, bone composition or bone resorption, nor did it augment the Na-induced calciuria or increased rate of bone resorption.

Nitrogen Homoeostasis in man: The Diurnal Responses of Protein Synthesis and Degradation and Amino Acid Oxidation to Diets with Increasing Protein Intakes

1994 ◽  
Vol 86 (1) ◽  
pp. 103-118 ◽  
Author(s):  
Paul J. Pacy ◽  
Gill M. Price ◽  
David Halliday ◽  
Marcello R. Quevedo ◽  
D. Joe Millward
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Dietary Protein ◽  
Protein Turnover ◽  
Protein Intake ◽  
Whole Body ◽  
Body Protein ◽  
Fed State ◽  
Leucine Kinetics ◽  
Synthesis And Degradation

1. The diurnal changes in whole body protein turnover associated with the increasing fasting body nitrogen (N) losses and feeding gains with increasing protein intake were investigated in normal adults. [13C]Leucine, [2H5]phenylalanine and [2H2]tyrosine kinetics, were measured during an 8h primed, continuous infusion during the fasting and feeding phase together with fed-state N turnover assessed with [15N]glycine after 12 days of adaptation to diets containing 0.36 (LP), 0.77 (MP), 1.59 (GP) and 2.07 (HP) g of protein day−1 kg−1. Measurements were also made of fasting and fed resting metabolic rate and plasma hormone levels. 2. Resting metabolic rate in the fasted and fed state was not influenced by dietary protein intake, but was increased by feeding (11-13%, P <0.01) with no influence of dietary protein concentration. Fasting plasma insulin levels were not influenced by protein intake and were increased by feeding independent of protein intake. Fasted but not fed values of insulinlike growth factor-1 increased with protein intake, although no feeding response was observed. Thyroid hormones (free and total tri-iodothyronine) did not change in any state. 3. For leucine with increasing protein intake the increasing fasting losses reflected increasing rates of protein degradation, although the changes were small and only significant between GP and MP intakes. The increasing leucine gain on feeding was associated with increasing rates of protein synthesis and falling rates of protein degradation, reflecting a progressive inhibition of degradation with feeding, and a change from inhibition of synthesis (LP diet) to stimulation (GP and HP diets). Mean daily rates of synthesis and degradation did not change with protein intake. 4. Phenylalanine and tyrosine kinetics were calculated from adjusted values based on leucine kinetics and published data of the hepatic/plasma enrichment ratio. With the increased protein intake, the increasing fasting losses of phenylalanine (GP > MP) were mediated by increasing rates of degradation (paired t-tests). The increasing phenylalanine gain (GP > MP > LP) was due to increasing fed-state rates of synthesis and falling rates of degradation, reflecting a progressive inhibition of degradation, a stimulation of hydroxylation and a variable response of synthesis ranging from inhibition at the lowest intake to stimulation at higher intakes. For tyrosine a similar progressive inhibition of degradation with intake was shown. Mean daily rates of synthesis and degradation (phenylalanine) and degradation (tyrosine) did not change with protein intake. 5. Estimation of protein turnover from 15N excretion in urea and ammonia during 9 h after 1 h intravenous infusion of [15N]glycine in the fed state on the LP, MP and GP diets indicated that neither synthesis nor degradation were influenced by dietary protein level. Synthesis estimated from 15N kinetics was significantly correlated with that determined from leucine kinetics (r = 0.78, n = 14, P <0.01) and from phenylalanine kinetics (r = 0.53, n = 14, P <0.05), and degradation estimated from 15N kinetics was significantly correlated with that determined from leucine kinetics (r = 0.60, n = 14, P <0.05). Thus the [15N]glycine, [13C]leucine and [2H5]phenylalanine methods gave broadly comparable results. 6. We conclude that the feeding response of protein synthesis, degradation and amino acid oxidation reflects the combined impact of insulin and tissue amino acid levels with insulin inhibiting degradation and with amino acids both stimulating synthesis and oxidation and also further inhibiting degradation. Although the dietary protein level influences the extent of these feeding responses, it does not influence the mean daily rate of protein turnover. The rate of whole body protein turnover per se is unlikely to provide an indicator of protein nutritional status.

Influence of dietary protein intake on whole‐body protein turnover in chicks

1987 ◽  
Vol 28 (3) ◽  
pp. 471-482 ◽  
Author(s):  
T. Muramatsu ◽  
K. Kita ◽  
I. Tasaki ◽  
J. Okumura
Keyword(s):  
Dietary Protein ◽  
Protein Turnover ◽  
Protein Intake ◽  
Whole Body ◽  
Dietary Protein Intake ◽  
Body Protein
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