PMID- 35366314 OWN - NLM STAT- MEDLINE DCOM- 20220502 LR - 20230403 IS - 1525-3163 (Electronic) IS - 0021-8812 (Print) IS - 0021-8812 (Linking) VI - 100 IP - 4 DP - 2022 Apr 1 TI - Leucine alters blood parameters and regulates hepatic protein synthesis via mammalian/mechanistic target of rapamycin activation in intrauterine growth-restricted piglets. LID - 10.1093/jas/skac109 [doi] LID - skac109 AB - Neonatal piglets often suffer low birth weights and poor growth performance accompanied by the disruption of protein metabolism, when intrauterine growth restriction (IUGR) takes place during pregnancy, leading to a higher mortality and bigger economic loss than expected. Leucine has been proposed to function as a nutritional signal-regulating protein synthesis in numerous studies. The aim of this study was to determine the effect of dietary leucine supplementation on the blood parameters and hepatic protein metabolism in IUGR piglets. Weaned piglets were assigned to one of four treatments in a 2 x 2 factorial arrangement: 1) piglets fed a basal diet with normal birth weight, 2) piglets fed a basal diet plus 0.35% l-leucine with normal birth weight, 3) IUGR piglets fed a basal diet with low birth weight, and 4) IUGR piglets fed a basal diet plus 0.35% l-leucine with low birth weight. The results showed that IUGR decreased serum aspartate aminotransferase and alkaline phosphatase activities and increased serum cortisol and prostaglandin E2 levels at 35 d of age (P < 0.05), suggesting the occurrence of liver dysfunction and stress response. Leucine supplementation increased serum alkaline phosphatase activity and decreased serum cortisol levels at 35 d of age (P < 0.05). IUGR decreased the lysozyme activity and complement 3 level in serum (P < 0.05), which were prevented by dietary leucine supplementation. IUGR piglets showed increased hepatic DNA contents while showing a reduced RNA/DNA ratio (P < 0.05). Piglets supplied with leucine had decreased RNA/DNA ratio in the liver (P < 0.05). Leucine supplementation stimulated hepatic protein anabolism through upregulating protein synthesis-related genes expression and activating the phosphorylation of mammalian/mechanistic target of rapamycin (mTOR) (P < 0.05). Moreover, IUGR inhibited the mRNA expression of hepatic protein degradation-related genes, indicating a compensatory mechanism for the metabolic response. Dietary leucine supplementation attenuated the suppression of the protein catabolism induced by IUGR in the liver. These results demonstrate that dietary leucine supplementation could alter the blood parameters and alleviated the disrupted protein metabolism induced by IUGR via enhanced mTOR phosphorylation to promote protein synthesis in weaned piglets. CI - (c) The Author(s) 2022. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. 
For permissions, please e-mail: journals.permissions@oup.com. FAU - Zhang, Jingfei AU - Zhang J AD - College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China. FAU - Xu, Wen AU - Xu W AD - College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China. FAU - Yang, Yuxiang AU - Yang Y AD - Department of Research and Innovation, Bluestar Adisseo Nanjing Co. Ltd., Nanjing 210000, China. FAU - Zhang, Lili AU - Zhang L AD - College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China. FAU - Wang, Tian AU - Wang T AUID- ORCID: 0000-0002-9038-5009 AD - College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China. LA - eng PT - Journal Article PL - United States TA - J Anim Sci JT - Journal of animal science JID - 8003002 RN - 63231-63-0 (RNA) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 3.1.3.1 (Alkaline Phosphatase) RN - GMW67QNF9C (Leucine) RN - W36ZG6FT64 (Sirolimus) RN - WI4X0X7BPJ (Hydrocortisone) SB - IM MH - Alkaline Phosphatase/metabolism MH - Animals MH - Animals, Newborn MH - Birth Weight MH - *Dietary Supplements MH - Female MH - *Fetal Growth Retardation/metabolism/veterinary MH - Hydrocortisone/metabolism MH - Leucine/metabolism/pharmacology MH - Liver/metabolism MH - Mammals/genetics/metabolism MH - Pregnancy MH - Protein Biosynthesis MH - RNA/metabolism MH - Sirolimus/pharmacology MH - Swine MH - TOR Serine-Threonine Kinases/metabolism PMC - PMC9053099 OAB - Intrauterine growth restriction (IUGR) produces a notable disturbance of protein metabolism in piglets, leading to lower birth weights and economic loss. Leucine supplementation positively regulates protein metabolism in animals and has the potential to recover the impaired balance between protein synthesis and degradation. Our study showed that leucine supplementation alleviated the abnormal changes in blood parameters and stimulated protein synthesis through the mammalian/mechanistic target of rapamycin signal pathway in the liver. Leucine supplementation attenuated the suppression of protein degradation induced by IUGR, which might be involved in a hepatic compensatory mechanism contributing to health status. OABL- eng OTO - NOTNLM OT - intrauterine growth restriction OT - leucine OT - piglets OT - protein degradation OT - protein synthesis EDAT- 2022/04/03 06:00 MHDA- 2022/05/03 06:00 PMCR- 2023/04/02 CRDT- 2022/04/02 17:04 PHST- 2022/03/03 00:00 [received] PHST- 2022/03/29 00:00 [accepted] PHST- 2022/04/03 06:00 [pubmed] PHST- 2022/05/03 06:00 [medline] PHST- 2022/04/02 17:04 [entrez] PHST- 2023/04/02 00:00 [pmc-release] AID - 6562689 [pii] AID - skac109 [pii] AID - 10.1093/jas/skac109 [doi] PST - ppublish SO - J Anim Sci. 2022 Apr 1;100(4):skac109. doi: 10.1093/jas/skac109.