In low protein diets, microRNA-19b regulates urea synthesis by targeting SIRT5.
Ammonia detoxification, which takes place via the hepatic urea cycle, is essential for nitrogen homeostasis and physiological well-being. It has been reported that a reduction in dietary protein reduces urea nitrogen. MicroRNAs (miRNAs) are major regulatory non-coding RNAs that have significant effects on several metabolic pathways; however, little is known on whether miRNAs regulate hepatic urea synthesis. The objective of this study was to assess the miRNA expression profile in a low protein diet and identify miRNAs involved in the regulation of the hepatic urea cycle using a porcine model. Weaned 28-days old piglets were fed a corn-soybean normal protein diet (NP) or a corn-soybean low protein diet (LP) for 30 d. Hepatic and blood samples were collected, and the miRNA expression profile was assessed by sequencing and qRT-PCR. Furthermore, we evaluated the possible role of miR-19b in urea synthesis regulation. There were 25 differentially expressed miRNAs between the NP and LP groups. Six of these miRNAs were predicted to be involved in urea cycle metabolism. MiR-19b negatively regulated urea synthesis by targeting SIRT5, which is a positive regulator of CPS1, the rate limiting enzyme in the urea cycle. Our study presented a novel explanation of ureagenesis regulation by miRNAs.
College of Animal Science, Chinese National Centre of Pig Breeding Technology, ALLTECH-SCAU Animal Nutrition Control Research Alliance, National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, 483 Wushan Road, Guangzhou, 510642, China.|Institute of Animal Science and Veterinary Medicine, Hainan Academy of Agricultural Science, Haikou 571100, China.
Rui-Ping
RP
Sun
College of Animal Science, Chinese National Centre of Pig Breeding Technology, ALLTECH-SCAU Animal Nutrition Control Research Alliance, National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, 483 Wushan Road, Guangzhou, 510642, China.
Qian-Yun
QY
Xi
College of Animal Science, Chinese National Centre of Pig Breeding Technology, ALLTECH-SCAU Animal Nutrition Control Research Alliance, National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, 483 Wushan Road, Guangzhou, 510642, China.
Jia-Jie
JJ
Sun
College of Animal Science, Chinese National Centre of Pig Breeding Technology, ALLTECH-SCAU Animal Nutrition Control Research Alliance, National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, 483 Wushan Road, Guangzhou, 510642, China.
Xiao
X
Cheng
College of Animal Science, Chinese National Centre of Pig Breeding Technology, ALLTECH-SCAU Animal Nutrition Control Research Alliance, National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, 483 Wushan Road, Guangzhou, 510642, China.
Yan-Ling
YL
Zhu
College of Animal Science, Chinese National Centre of Pig Breeding Technology, ALLTECH-SCAU Animal Nutrition Control Research Alliance, National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, 483 Wushan Road, Guangzhou, 510642, China.
Ding-Ze
DZ
Ye
College of Animal Science, Chinese National Centre of Pig Breeding Technology, ALLTECH-SCAU Animal Nutrition Control Research Alliance, National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, 483 Wushan Road, Guangzhou, 510642, China.
Ting
T
Chen
College of Animal Science, Chinese National Centre of Pig Breeding Technology, ALLTECH-SCAU Animal Nutrition Control Research Alliance, National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, 483 Wushan Road, Guangzhou, 510642, China.|Institute of Animal Science and Veterinary Medicine, Hainan Academy of Agricultural Science, Haikou 571100, China.
Li-Min
LM
Wei
College of Animal Science, Chinese National Centre of Pig Breeding Technology, ALLTECH-SCAU Animal Nutrition Control Research Alliance, National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, 483 Wushan Road, Guangzhou, 510642, China.
Rui-Song
RS
Ye
College of Animal Science, Chinese National Centre of Pig Breeding Technology, ALLTECH-SCAU Animal Nutrition Control Research Alliance, National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, 483 Wushan Road, Guangzhou, 510642, China.
Qing-Yan
QY
Jiang
College of Animal Science, Chinese National Centre of Pig Breeding Technology, ALLTECH-SCAU Animal Nutrition Control Research Alliance, National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, 483 Wushan Road, Guangzhou, 510642, China.
Yong-Liang
YL
Zhang
Metabolism. 2012 Nov;61(11):1495-511
22921946
Sci Rep. 2016 Jan 12;6:18493
26755400
J Virol. 2016 Apr 14;90(9):4780-4795
26937036
Biochem Biophys Res Commun. 2015 Feb 6;457(2):171-6
25542152
Clin J Am Soc Nephrol. 2015 Aug 7;10(8):1444-58
25078422
J Zhejiang Univ Sci B. 2015 Jun;16(6):496-502
26055911
Mol Endocrinol. 1988 May;2(5):444-51
2843756
Sci Rep. 2015 Nov 04;5:16132
26531148
J Anim Sci. 2011 Dec;89(12):4116-9
21821811
Comp Biochem Physiol B Biochem Mol Biol. 1998 Mar;119(3):527-37
9734336
Enzyme. 1981;26(3):113-21
7250092
Cell Metab. 2012 Mar 7;15(3):311-23
22405069
Gene. 2007 Dec 1;404(1-2):25-30
17904311
Cancer Sci. 2010 Oct;101(10):2087-92
20624164
Exp Cell Res. 1973 Dec;82(2):391-8
4358115
Cell Metab. 2014 Apr 1;19(4):605-17
24703693
Aging Cell. 2011 Oct;10(5):769-79
21501375
Nature. 2005 Mar 31;434(7033):652-8
15800626
RNA Biol. 2012 Feb;9(2):137-42
22258222
Immunity. 2013 May 23;38(5):984-97
23623381
Methods Mol Biol. 2013;1012:187-200
24006065
Sci China Life Sci. 2015 Sep;58(9):912-4
26208827
Amino Acids. 2009 May;37(1):1-17
19301095
Cell. 2009 May 1;137(3):560-70
19410549
J Gastroenterol. 2012 Aug;47(8):883-95
22382630
PLoS One. 2012;7(6):e38716
22719927
Mol Genet Metab. 2010;100 Suppl 1:S3-S12
20227314
BMC Genomics. 2014 Feb 05;15:100
24499489
Mol Cell Biol. 1998 Nov;18(11):6305-15
9774647
J Anim Sci. 2002 Nov;80(11):2911-9
12462259
Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9468-72
1682918
Aust J Biol Sci. 1988;41(4):435-40
3271380
Amino Acids. 2013 Apr;44(4):1107-13
23247926
Nucleic Acids Res. 2005 Nov 27;33(20):e179
16314309
Mol Cell Biol. 2013 Aug;33(15):2891-902
23716591
Dev Biol. 2007 Oct 15;310(2):442-53
17765889
Biochem Biophys Res Commun. 2010 Feb 26;393(1):73-8
20097174
BMC Genomics. 2013 Jun 13;14:395
23758991
Mol Genet Metab Rep. 2016 Jan 21;6:34-40
27014577
Amino Acids. 2009 May;37(1):105-10
18670730
J Hepatol. 2015 Feb;62(2):448-57
25308172
Cell. 2009 Jun 12;137(6):1005-17
19524505
Genes Dev. 2009 Dec 15;23(24):2806-11
20008931
J Anim Sci. 2005 Apr;83(4):879-89
15753344
Mol Biol Rep. 2012 Dec;39(12):10987-96
23053988
Cell. 2004 Jan 23;116(2):281-97
14744438
Br J Nutr. 2013 May 28;109(10):1731-8
22958366
Hum Mutat. 2010 Jul;31(7):801-8
20578160
Stem Cells. 2016 May;34(5):1284-96
26731713
J Cell Mol Med. 2016 May;20(5):939-48
26781774
J Hepatol. 2008 Apr;48(4):648-56
18291553
Annu Rev Nutr. 1992;12:81-101
1503815
Annu Rev Nutr. 2002;22:87-105
12055339
Oncotarget. 2015 Apr 10;6(10):8089-102
25797269