title: L-Arginine promotes protein synthesis and cell growth in brown adipocyte precursor cells via the mTOR signal pathway.
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, P70S6Kand 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.
authors.affiliation: State Key Laboratory of Animal Nutrition, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing, 100193, China.|Department of Animal Science, Texas A&M University, College Station, TX, 77843-2471, USA.
authors.forename: Xi
authors.initials: X
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Animal Nutrition, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing, 100193, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Han
authors.affiliation: State Key Laboratory of Animal Nutrition, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing, 100193, China.
authors.forename: Defa
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Animal Science, Texas A&M University, College Station, TX, 77843-2471, USA.
authors.forename: Shengdi
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Animal Science, Texas A&M University, College Station, TX, 77843-2471, USA.
authors.forename: Kyler R
authors.initials: KR
authors.lastname: Gilbreath
authors.affiliation: Department of Animal Science, Texas A&M University, College Station, TX, 77843-2471, USA.
authors.forename: Fuller W
authors.initials: FW
authors.lastname: Bazer
authors.affiliation: State Key Laboratory of Animal Nutrition, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing, 100193, China. g-wu@tamu.edu.|Department of Animal Science, Texas A&M University, College Station, TX, 77843-2471, USA. g-wu@tamu.edu.
authors.forename: Guoyao
authors.initials: G
authors.lastname: Wu
mesh_terms: D052437:Adipocytes, Brown / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D039642:Eukaryotic Initiation Factors / Q000235:genetics / Q000378:metabolism; D005260:Female; D005333:Fetus; D018507:Gene Expression Regulation, Developmental; D009765:Obesity / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics / Q000378:metabolism; D034561:Sheep, Domestic; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D000071256:Uncoupling Protein 1 / Q000235:genetics / Q000378:metabolism; D016335:Zinc Fingers / Q000235:genetics
chemical_list: D055419:Bone Morphogenetic Protein 7; D039642:Eukaryotic Initiation Factors; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D000071256:Uncoupling Protein 1; D001120:Arginine; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases
keywords: Brown adipocytes; Cell proliferation; L-Arginine; Protein turnover; UCP1; mTOR