Leucine Supplementation Does Not Restore Diminished Skeletal Muscle Satellite Cell Abundance and Myonuclear Accretion When Protein Intake Is Limiting in Neonatal Pigs

ABSTRACT Background Rapid growth of skeletal muscle in the neonate requires the coordination of protein deposition and myonuclear accretion. During this developmental stage, muscle protein synthesis is highly sensitive to amino acid supply, especially Leu, but we do not know if this is true for satellite cells, the source of muscle fiber myonuclei. Objective We examined whether dietary protein restriction reduces myonuclear accretion in the neonatal pig, and if any reduction in myonuclear accretion is mitigated by restoring Leu intake. Methods Neonatal pigs (1.53 ± 0.2 kg) were fitted with jugular vein and gastric catheters and fed 1 of 3 isoenergetic milk replacers every 4 h for 21 d: high protein [HP; 22.5 g protein/(kg/d); n= 8]; restricted protein [RP; 11.2 g protein/(kg/d); n= 10]; or restricted protein with Leu [RPL; 12.0 g protein/(kg/d); n= 10]. Pigs were administered 5-bromo-2’-deoxyuridine (BrdU; 15 mg/kg) intravenously every 12 h from days 6 to 8. Blood was sampled on days 6 and 21 to measure plasma Leu concentrations. On day 21, pigs were killed and the longissimus dorsi (LD) muscle was collected to measure cell morphometry, satellite cell abundance, myonuclear accretion, and insulin-like growth factor (IGF) system expression. Results Compared with HP pigs, postprandial plasma Leu concentration in RP pigs was 37% and 47% lower on days 6 and 21, respectively (P < 0.05); Leu supplementation in RPL pigs restored postprandial Leu to HP concentrations. Dietary protein restriction reduced LD myofiber cross-sectional area by 21%, satellite cell abundance by 35%, and BrdU+ myonuclear abundance by 25% (P < 0.05); Leu did not reverse these outcomes. Dietary protein restriction reduced LD muscle IGF2 expression by 60%, but not IGF1 or IGF1R expression (P < 0.05); Leu did not rescue IGF2 expression. Conclusions Satellite cell abundance and myonuclear accretion in neonatal pigs are compromised when dietary protein intake is restricted and are not restored with Leu supplementation.

Download Full-text

Effects of dietary protein restriction on regional amino acid metabolism in insulin-dependent diabetes mellitus

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1996.270.1.e148 ◽

1996 ◽

Vol 270 (1) ◽

pp. E148-E157 ◽

Cited By ~ 2

Author(s):

I. G. Brodsky ◽

J. T. Devlin

Keyword(s):

Diabetes Mellitus ◽

Dietary Protein ◽

Protein Intake ◽

Insulin Dependent Diabetes Mellitus ◽

Protein Restriction ◽

Insulin Dependent Diabetes ◽

Whole Body ◽

Dependent Diabetes Mellitus ◽

Dietary Protein Restriction ◽

Insulin Dependent

We studied subjects with insulin-dependent diabetes mellitus (IDDM) and controls by administering primed continuous infusions of L-[1-13C,15N)]leucine and L-[2,3-13C2]alanine to measure whole body and forearm metabolism of these amino acids during ample protein intake and again after 4 wk of moderately restricted protein intake. Decreased rates of whole body protein degradation, leucine transamination, leucine oxidation, and increased forearm alanine release produced by dietary protein restriction occurred equivalently in IDDM subjects under short-term tightly managed glycemia and in controls. Dietary protein restriction did not affect whole body alanine appearance or forearm leucine appearance, disposal, or balance in IDDM subjects or controls. IDDM subjects differed from controls only in that normal forearm leucine balance was maintained at higher rates of leucine appearance and disposal. We conclude that IDDM subjects adapt normally to dietary protein restriction. Undernutrition during moderate protein deprivation in these patients likely occurs during episodes of poor glycemic control.

Download Full-text

Proximal tubule glutamine synthetase expression is necessary for the normal response to dietary protein restriction

AJP Renal Physiology ◽

10.1152/ajprenal.00048.2017 ◽

2017 ◽

Vol 313 (1) ◽

pp. F116-F125 ◽

Cited By ~ 9

Author(s):

Hyun-Wook Lee ◽

Gunars Osis ◽

Mary E. Handlogten ◽

Jill W. Verlander ◽

I. David Weiner

Keyword(s):

Glutamine Synthetase ◽

Proximal Tubule ◽

Dietary Protein ◽

Acid Production ◽

Protein Intake ◽

Ammonia Excretion ◽

Protein Restriction ◽

Protein Diet ◽

Acid Excretion ◽

Dietary Protein Restriction

Dietary protein restriction has multiple benefits in kidney disease. Because protein intake is a major determinant of endogenous acid production, it is important that net acid excretion changes in parallel during changes in dietary protein intake. Dietary protein restriction decreases endogenous acid production and decreases urinary ammonia excretion, a major component of net acid excretion. Glutamine synthetase (GS) catalyzes the reaction of [Formula: see text] and glutamate, which regenerates the essential amino acid glutamine and decreases net ammonia generation. Because renal proximal tubule GS expression increases during dietary protein restriction, this could contribute to the decreased ammonia excretion. The purpose of the current study was to determine the role of proximal tubule GS in the renal response to protein restriction. We generated mice with proximal tubule-specific GS deletion (PT-GS-KO) using Cre-loxP techniques. Cre-negative (Control) and PT-GS-KO mice in metabolic cages were provided 20% protein diet for 2 days and were then changed to low-protein (6%) diet for the next 7 days. Additional PT-GS-KO mice were maintained on 20% protein diet. Dietary protein restriction caused a rapid decrease in urinary ammonia excretion in both genotypes, but PT-GS-KO blunted this adaptive response significantly. This occurred despite no significant genotype-dependent differences in urinary pH or in serum electrolytes. There were no significant differences between Control and PT-GS-KO mice in expression of multiple other proteins involved in renal ammonia handling. We conclude that proximal tubule GS expression is necessary for the appropriate decrease in ammonia excretion during dietary protein restriction.

Download Full-text

Effects of dietary protein restriction on muscle fiber characteristics and mTORC1 pathway in the skeletal muscle of growing-finishing pigs

Journal of Animal Science and Biotechnology ◽

10.1186/s40104-016-0106-8 ◽

2016 ◽

Vol 7 (1) ◽

Cited By ~ 15

Author(s):

Yinghui Li ◽

Fengna Li ◽

Li Wu ◽

Hongkui Wei ◽

Yingying Liu ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Fiber ◽

Dietary Protein ◽

Protein Restriction ◽

Finishing Pigs ◽

Dietary Protein Restriction ◽

Mtorc1 Pathway

Download Full-text

The Effect of Severe Dietary Protein Restriction on Skeletal Muscle Fiber Number, Area and Composition in Weanling Rats

Journal of Animal Science ◽

10.2527/jas1985.612416x ◽

1985 ◽

Vol 61 (2) ◽

pp. 416-422 ◽

Cited By ~ 2

Author(s):

B. F. Timson ◽

G. A. Dudenhoeffer

Keyword(s):

Skeletal Muscle ◽

Muscle Fiber ◽

Dietary Protein ◽

Protein Restriction ◽

Skeletal Muscle Fiber ◽

Dietary Protein Restriction ◽

Weanling Rats ◽

Fiber Number ◽

Muscle Fiber Number

Download Full-text

Maternal dietary protein restriction and excess affects offspring gene expression and methylation of non-SMC subunits of condensin I in liver and skeletal muscle

Epigenetics ◽

10.4161/epi.7.3.19183 ◽

2012 ◽

Vol 7 (3) ◽

pp. 239-252 ◽

Cited By ~ 43

Author(s):

Simone Altmann ◽

Eduard Murani ◽

Manfred Schwerin ◽

Cornelia C. Metges ◽

Klaus Wimmers ◽

...

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Dietary Protein ◽

Protein Restriction ◽

Dietary Protein Restriction

Download Full-text

FGF21 and the Physiological Regulation of Macronutrient Preference

Endocrinology ◽

10.1210/endocr/bqaa019 ◽

2020 ◽

Vol 161 (3) ◽

Cited By ~ 4

Author(s):

Cristal M Hill ◽

Emily Qualls-Creekmore ◽

Hans-Rudolf Berthoud ◽

Paul Soto ◽

Sangho Yu ◽

...

Keyword(s):

Dietary Protein ◽

Protein Intake ◽

Protein Restriction ◽

Fibroblast Growth Factor 21 ◽

Adaptive Responses ◽

Ample Evidence ◽

Dietary Protein Restriction ◽

The Face ◽

Increase Protein Intake ◽

The Brain

Abstract The ability to respond to variations in nutritional status depends on regulatory systems that monitor nutrient intake and adaptively alter metabolism and feeding behavior during nutrient restriction. There is ample evidence that the restriction of water, sodium, or energy intake triggers adaptive responses that conserve existing nutrient stores and promote the ingestion of the missing nutrient, and that these homeostatic responses are mediated, at least in part, by nutritionally regulated hormones acting within the brain. This review highlights recent research that suggests that the metabolic hormone fibroblast growth factor 21 (FGF21) acts on the brain to homeostatically alter macronutrient preference. Circulating FGF21 levels are robustly increased by diets that are high in carbohydrate but low in protein, and exogenous FGF21 treatment reduces the consumption of sweet foods and alcohol while alternatively increasing the consumption of protein. In addition, while control mice adaptively shift macronutrient preference and increase protein intake in response to dietary protein restriction, mice that lack either FGF21 or FGF21 signaling in the brain fail to exhibit this homeostatic response. FGF21 therefore mediates a unique physiological niche, coordinating adaptive shifts in macronutrient preference that serve to maintain protein intake in the face of dietary protein restriction.

Download Full-text