Abstract
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-1α) pathway. These findings reveal a vital regulatory role of leucine as the signal molecule involved in an energy metabolism switch in mammals.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 42-56 |
| Number of pages | 15 |
| Journal | International Journal of Biochemistry and Cell Biology |
| Volume | 89 |
| DOIs | |
| State | Published - Aug 1 2017 |
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Keywords
- Glycolysis
- HIF-1α
- Leucine
- mTOR
- Oxidative phosphorylation
- Reactive oxygen species
ASJC Scopus subject areas
- Biochemistry
- Cell Biology
Cite this
Leucine reduces reactive oxygen species levels via an energy metabolism switch by activation of the mTOR-HIF-1α pathway in porcine intestinal epithelial cells. / Hu, Jun; Nie, Yangfan; Chen, Shifeng; Xie, Chunlin; Fan, Qiwen; Wang, Zhichang; Long, Baisheng; Yan, Guokai; Zhong, Qing; Yan, Xianghua.
In: International Journal of Biochemistry and Cell Biology, Vol. 89, 01.08.2017, p. 42-56.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Leucine reduces reactive oxygen species levels via an energy metabolism switch by activation of the mTOR-HIF-1α pathway in porcine intestinal epithelial cells
AU - Hu, Jun
AU - Nie, Yangfan
AU - Chen, Shifeng
AU - Xie, Chunlin
AU - Fan, Qiwen
AU - Wang, Zhichang
AU - Long, Baisheng
AU - Yan, Guokai
AU - Zhong, Qing
AU - Yan, Xianghua
PY - 2017/8/1
Y1 - 2017/8/1
N2 - 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-1α) pathway. These findings reveal a vital regulatory role of leucine as the signal molecule involved in an energy metabolism switch in mammals.
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-1α) pathway. These findings reveal a vital regulatory role of leucine as the signal molecule involved in an energy metabolism switch in mammals.
KW - Glycolysis
KW - HIF-1α
KW - Leucine
KW - mTOR
KW - Oxidative phosphorylation
KW - Reactive oxygen species
UR - http://www.scopus.com/inward/record.url?scp=85020237871&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85020237871&partnerID=8YFLogxK
U2 - 10.1016/j.biocel.2017.05.026
DO - 10.1016/j.biocel.2017.05.026
M3 - Article
C2 - 28583467
AN - SCOPUS:85020237871
VL - 89
SP - 42
EP - 56
JO - International Journal of Biochemistry and Cell Biology
JF - International Journal of Biochemistry and Cell Biology
SN - 1357-2725
ER -