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In low protein diets, microRNA-19b regulates urea synthesis by targeting SIRT5.

ABSTRACT: 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.

SUBMITTER: Sun RP

PROVIDER: S-EPMC5043173 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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In low protein diets, microRNA-19b regulates urea synthesis by targeting SIRT5.

Sun Rui-Ping RP Xi Qian-Yun QY Sun Jia-Jie JJ Cheng Xiao X Zhu Yan-Ling YL Ye Ding-Ze DZ Chen Ting T Wei Li-Min LM Ye Rui-Song RS Jiang Qing-Yan QY Zhang Yong-Liang YL

Scientific reports 20160930

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 d ...[more]

PMID: 27686746

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Project description:Twenty-eight lactating Yorkshire and Yorkshire × Landrace primiparous sows were used to test the hypothesis that feeding a diet with reduced CP concentration and supplemented with crystalline AA (CAA) does not decrease milk protein yield and litter growth but improves apparent N utilization for milk protein production. Sows were assigned to 1 of 2 dietary treatments: 1) control (CON; 16.2% CP; analyzed content) or 2) low CP with CAA to meet estimated requirements of limiting AA (LCP; 12.7% CP) over a 17-d lactation period. A N balance was conducted for each sow between days 13 and 17 of lactation. On day 17, a 12-h primed continuous infusion of l-[ring-2H5]-Phe was conducted on 12 sows (n = 6) with serial blood and milk sampling to determine plasma AA concentrations and Phe enrichment, and milk casein synthesis, respectively. Thereafter, sows were sacrificed and tissues were collected to determine tissue protein fractional synthesis rates (FSR). Litter growth rate and milk composition did not differ. Sows fed the LCP diet had reduced N intake (122.7 vs. 153.2 g/d; P < 0.001) and maternal N retention (13.5 vs. 24.6 g/d; P < 0.05) and greater apparent efficiency of using dietary N intake for milk production (85.1% vs. 67.5%; P < 0.001). On day 17 of lactation, all plasma essential AA concentrations exhibited a quartic relationship over time relative to consumption of a meal, where peaks occurred at approximately 1- and 4-h postprandial (P < 0.05). Protein FSR in liver, LM, gastrocnemius muscle, mammary gland, and in milk caseins did not differ between treatments. Feeding primiparous sows with a diet containing 12.7% CP and supplemented with CAA to meet the limiting AA requirements did not reduce milk protein yield or piglet growth rate and increased the apparent utilization of dietary N, Arg, Leu, Phe+Tyr, and Trp for milk protein production. The improved apparent utilization of N and AA appears to be related exclusively to a reduction in N and AA intake.

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In low protein diets, microRNA-19b regulates urea synthesis by targeting SIRT5.

Publications

In low protein diets, microRNA-19b regulates urea synthesis by targeting SIRT5.

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