PMID- 28583467 OWN - NLM STAT- MEDLINE DCOM- 20171120 LR - 20211204 IS - 1878-5875 (Electronic) IS - 1357-2725 (Linking) VI - 89 DP - 2017 Aug TI - Leucine reduces reactive oxygen species levels via an energy metabolism switch by activation of the mTOR-HIF-1alpha pathway in porcine intestinal epithelial cells. PG - 42-56 LID - S1357-2725(17)30124-3 [pii] LID - 10.1016/j.biocel.2017.05.026 [doi] AB - Leucine serves not only as a substrate for protein synthesis, but also as a signal molecule involved in protein metabolism. However, whether the levels of cellular reactive oxygen species (ROS), which have damaging effects on cellular DNA, proteins, and lipids, are regulated by leucine is still unclear. Here, we report that leucine supplementation reduces ROS levels in intestinal epithelial cells of weaned piglets. A proteomics analysis revealed that leucine supplementation induces an energy metabolism switch from oxidative phosphorylation (OXPHOS) towards glycolysis. The leucine-induced ROS reduction and the energy metabolism switch were further validated in cultured cells. Mechanistically, our data revealed that leucine-induced ROS reduction actually depends on the energy metabolism switch from OXPHOS towards glycolysis through the mechanistic target of rapamycin (mTOR)- hypoxia-inducible factor-1alpha (HIF-1alpha) pathway. These findings reveal a vital regulatory role of leucine as the signal molecule involved in an energy metabolism switch in mammals. CI - Copyright (c) 2017 Elsevier Ltd. All rights reserved. FAU - Hu, Jun AU - Hu J AD - College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, 430070, Hubei, China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, Hubei, China; Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Technology, Wuhan, 430070, Hubei, China. Electronic address: hujun891732@sina.com. FAU - Nie, Yangfan AU - Nie Y AD - College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, 430070, Hubei, China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, Hubei, China; Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Technology, Wuhan, 430070, Hubei, China. Electronic address: yangfannie@sina.com. FAU - Chen, Shifeng AU - Chen S AD - College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, 430070, Hubei, China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, Hubei, China; Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Technology, Wuhan, 430070, Hubei, China. Electronic address: csf9347@163.com. FAU - Xie, Chunlin AU - Xie C AD - College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, 430070, Hubei, China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, Hubei, China; Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Technology, Wuhan, 430070, Hubei, China. Electronic address: cylinqueen@163.com. FAU - Fan, Qiwen AU - Fan Q AD - College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, 430070, Hubei, China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, Hubei, China; Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Technology, Wuhan, 430070, Hubei, China. Electronic address: asdzxcpall@sina.cn. FAU - Wang, Zhichang AU - Wang Z AD - College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, 430070, Hubei, China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, Hubei, China; Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Technology, Wuhan, 430070, Hubei, China. Electronic address: wzc997241525@163.com. FAU - Long, Baisheng AU - Long B AD - College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, 430070, Hubei, China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, Hubei, China; Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Technology, Wuhan, 430070, Hubei, China. Electronic address: longbs527@sina.com. FAU - Yan, Guokai AU - Yan G AD - College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, 430070, Hubei, China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, Hubei, China; Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Technology, Wuhan, 430070, Hubei, China. Electronic address: gkyang@163.com. FAU - Zhong, Qing AU - Zhong Q AD - Center for Autophagy Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: qing.zhong@utsouthwestern.edu. FAU - Yan, Xianghua AU - Yan X AD - College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, 430070, Hubei, China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, Hubei, China; Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Technology, Wuhan, 430070, Hubei, China. Electronic address: xhyan@mail.hzau.edu.cn. LA - eng PT - Journal Article DEP - 20170602 PL - Netherlands TA - Int J Biochem Cell Biol JT - The international journal of biochemistry & cell biology JID - 9508482 RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 0 (Reactive Oxygen Species) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - GMW67QNF9C (Leucine) SB - IM MH - Animals MH - Cell Line MH - Diet MH - Energy Metabolism/*drug effects MH - Glycolysis/drug effects MH - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism MH - Intestinal Mucosa/*cytology MH - Leucine/*pharmacology MH - Oxidative Phosphorylation/drug effects MH - Reactive Oxygen Species/*metabolism MH - Signal Transduction/*drug effects MH - Swine MH - TOR Serine-Threonine Kinases/*metabolism OTO - NOTNLM OT - Glycolysis OT - HIF-1alpha OT - Leucine OT - Oxidative phosphorylation OT - Reactive oxygen species OT - mTOR EDAT- 2017/06/07 06:00 MHDA- 2017/11/29 06:00 CRDT- 2017/06/07 06:00 PHST- 2017/01/02 00:00 [received] PHST- 2017/05/23 00:00 [revised] PHST- 2017/05/24 00:00 [accepted] PHST- 2017/06/07 06:00 [pubmed] PHST- 2017/11/29 06:00 [medline] PHST- 2017/06/07 06:00 [entrez] AID - S1357-2725(17)30124-3 [pii] AID - 10.1016/j.biocel.2017.05.026 [doi] PST - ppublish SO - Int J Biochem Cell Biol. 2017 Aug;89:42-56. doi: 10.1016/j.biocel.2017.05.026. Epub 2017 Jun 2.