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l-Arginine promotes protein synthesis and cell growth in brown adipocyte precursor cells via the mTOR signal pathway

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Abstract

l-Arginine has been reported to enhance brown adipose tissue developments in fetal lambs of obese ewes, but the underlying mechanism is unknown. The present study tested the hypothesis that l-arginine stimulates growth and development of brown adipocyte precursor cells (BAPCs) through activation of mammalian target of rapamycin cell signaling. BAPCs isolated from fetal lambs at day 90 of gestation were incubated   for 6 h in arginine-free DMEM, and then cultured in DMEM with concentrations of 50, 100, 200, 500 or 1000 μmol l-arginine/L for 24–96 h. Cell proliferation, protein turnover, the mammalian target of rapamycin (mTOR) signaling pathway and pre-adipocyte differentiation markers were determined. l-arginine treatment enhanced (P < 0.05) BAPC growth and protein synthesis, while inhibiting proteolysis in a dose-dependent manner. Compared with 50 and 100 μmol/L (the concentrations of arginine in the maternal plasma of obese ewes), 200 μmol l-arginine/L (the concentrations of arginine in the maternal plasma of obese ewes receiving arginine supplementation) increased (P < 0.05) the abundances of phosphorylated mTOR, P70S6K and 4EBP1, as well as the abundances of PGC1α, UCP1, BMP7 and PRDM16. These novel findings indicate that increasing extra-cellular arginine concentration from 50 to 200 µmol/L activates mTOR cell signaling in BAPCs and enhances their growth and development in a dose-dependent manner. Our results provide a mechanism for arginine supplementation to enhance the development of brown adipose tissue in fetal lambs.

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Abbreviations

BAPCs:

Brown adipocyte precursor cells

BAT:

Brown adipose tissue

BMP7:

Bone morphogenetic protein 7

mTOR:

Mammalian target of rapamycin

p:

Phosphorylated

P70S6K :

Ribosomal protein S6 kinase

PGC1α:

PPARγ coactivator 1 alpha

PRDM16:

PRD1-BF1-RIZ1 homologous domain containing protein 16

UCP1:

Uncoupling protein 1

4E-BP1:

4E-binding protein 1

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Acknowledgements

This project was funded in part by China Scholarship Council, Texas A&M AgriLife Research (H-8200), the National Natural Science Foundation of China (Nos. 31528018, 31272448 and 31472101), the National Basic Research Program of China (973 Program, 2013CB117301), and the 111 Project (B16044).

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Authors and Affiliations

  1. State Key Laboratory of Animal Nutrition, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing, 100193, China

    Xi Ma, Meng Han, Defa Li & Guoyao Wu

  2. Department of Animal Science, Texas A&M University, College Station, TX, 77843-2471, USA

    Xi Ma, Shengdi Hu, Kyler R. Gilbreath, Fuller W. Bazer & Guoyao Wu

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  1. Xi Ma
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  2. Meng Han
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  3. Defa Li
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  4. Shengdi Hu
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  5. Kyler R. Gilbreath
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  6. Fuller W. Bazer
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  7. Guoyao Wu
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Correspondence to Guoyao Wu.

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Ethical statement

This study involved the culture of an existing cell line and did not require an animal use protocol.

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Ma, X., Han, M., Li, D. et al. l-Arginine promotes protein synthesis and cell growth in brown adipocyte precursor cells via the mTOR signal pathway. Amino Acids 49, 957–964 (2017). https://doi.org/10.1007/s00726-017-2399-0

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  • DOI: https://doi.org/10.1007/s00726-017-2399-0

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