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      Muscle free amino acid profiles are related to differences in skeletal muscle growth between single and twin ovine fetuses near term

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          Abstract

          Twin sheep fetuses have reduced skeletal muscle weight near birth relative to singles as a result of restricted muscle hypertrophy. Intracellular free amino acids (FAA) are reported to regulate metabolic pathways which control muscle protein accretion, whereby reduced intracellular content of specific FAA may reduce their activation and therefore, muscle hypertrophy. The aim of this study was to determine whether differences in muscle weight between singleton and twin fetuses, under different maternal conditions is associated with reduced concentration of specific FAA. The FAA content in the semitendinosus muscle (ST) in singleton and twin fetuses (rank) at 140 days of gestation from heavy (H) or light (L) ewes fed ad libitum (A) or maintenance (M) level of nutrition was measured. Muscle weight was reduced in twin fetuses compared to singletons in all groups. Reduced concentrations of leucine, threonine and valine, but higher concentrations of methionine, ornithine, lysine and serine were found in twin fetuses compared to singletons. Maternal size and nutrition interaction with rank resulted in reduced glutamine in twins from HM-ewes (H-ewes under M nutrition) compared to their singleton counterparts. Maternal weight interaction with pregnancy rank reduced the concentration of arginine in twins, with a larger effect on H-ewes compared with L-ewes. Maternal size interaction with pregnancy rank resulted in twins from M-ewes to have lower alanine, while twins from A-ewes had lower aspartic acid concentration compared to singletons. The ST muscle weight was positively correlated only with arginine concentration after taking into account rank, size and nutrition. The present results indicate that reduced concentrations of specific intracellular FAA, such as arginine, leucine, valine, glutamine, which are known to play a role in muscle growth, could be acting as limiting factors for muscle hypertrophy in twin fetuses during late gestation. Ewe size and nutrition can influence the concentration of specific FAA in muscle and should be considered in any intervention plan to improve twin fetal muscle growth.

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          Most cited references48

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          Bidirectional transport of amino acids regulates mTOR and autophagy.

          Amino acids are required for activation of the mammalian target of rapamycin (mTOR) kinase which regulates protein translation, cell growth, and autophagy. Cell surface transporters that allow amino acids to enter the cell and signal to mTOR are unknown. We show that cellular uptake of L-glutamine and its subsequent rapid efflux in the presence of essential amino acids (EAA) is the rate-limiting step that activates mTOR. L-glutamine uptake is regulated by SLC1A5 and loss of SLC1A5 function inhibits cell growth and activates autophagy. The molecular basis for L-glutamine sensitivity is due to SLC7A5/SLC3A2, a bidirectional transporter that regulates the simultaneous efflux of L-glutamine out of cells and transport of L-leucine/EAA into cells. Certain tumor cell lines with high basal cellular levels of L-glutamine bypass the need for L-glutamine uptake and are primed for mTOR activation. Thus, L-glutamine flux regulates mTOR, translation and autophagy to coordinate cell growth and proliferation.
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            In utero programming of chronic disease.

            1. Many human fetuses have to adapt to a limited supply of nutrients. In doing so they permanently change their structure and metabolism. 2. These 'programmed' changes may be the origins of a number of diseases in later life, including coronary heart disease and the related disorders stroke, diabetes and hypertension. 3. This review examines the evidence linking these diseases to fetal undernutrition and provides an overview of previous studies in this area.
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              Arginine metabolism and nutrition in growth, health and disease.

              L-Arginine (Arg) is synthesised from glutamine, glutamate, and proline via the intestinal-renal axis in humans and most other mammals (including pigs, sheep and rats). Arg degradation occurs via multiple pathways that are initiated by arginase, nitric-oxide synthase, Arg:glycine amidinotransferase, and Arg decarboxylase. These pathways produce nitric oxide, polyamines, proline, glutamate, creatine, and agmatine with each having enormous biological importance. Arg is also required for the detoxification of ammonia, which is an extremely toxic substance for the central nervous system. There is compelling evidence that Arg regulates interorgan metabolism of energy substrates and the function of multiple organs. The results of both experimental and clinical studies indicate that Arg is a nutritionally essential amino acid (AA) for spermatogenesis, embryonic survival, fetal and neonatal growth, as well as maintenance of vascular tone and hemodynamics. Moreover, a growing body of evidence clearly indicates that dietary supplementation or intravenous administration of Arg is beneficial in improving reproductive, cardiovascular, pulmonary, renal, gastrointestinal, liver and immune functions, as well as facilitating wound healing, enhancing insulin sensitivity, and maintaining tissue integrity. Additionally, Arg or L-citrulline may provide novel and effective therapies for obesity, diabetes, and the metabolic syndrome. The effect of Arg in treating many developmental and health problems is unique among AAs, and offers great promise for improved health and wellbeing of humans and animals.
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                Author and article information

                Contributors
                fsales@inia.cl
                david.pacheco@agresearch.co.nz
                H.Blair@massey.ac.nz
                P.R.Kenyon@massey.ac.nz
                sue.mccoard@agresearch.co.nz
                Journal
                Springerplus
                Springerplus
                SpringerPlus
                Springer International Publishing (Cham )
                2193-1801
                23 September 2013
                23 September 2013
                2013
                : 2
                : 483
                Affiliations
                [ ]Animal Nutrition Team, Animal Nutrition and Health Group, AgResearch, Grasslands Research Centre, Palmerston North, New Zealand
                [ ]Gravida: National Research Centre for Growth and Development, Auckland, New Zealand
                [ ]Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Palmerston North, New Zealand
                [ ]Instituto de Investigaciones Agropecuarias, Centro Regional Kampenaike, Punta Arenas, Chile
                Article
                567
                10.1186/2193-1801-2-483
                3795875
                24133643
                05e8ede3-1050-4622-a430-b558b0533fbc
                © Sales et al.; licensee Springer. 2013

                This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 27 June 2013
                : 4 September 2013
                Categories
                Research
                Custom metadata
                © The Author(s) 2013

                Uncategorized
                free amino acid,fetal muscle,gestation,muscle growth,sheep
                Uncategorized
                free amino acid, fetal muscle, gestation, muscle growth, sheep

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