PMID- 28000843
OWN - NLM
STAT- MEDLINE
DCOM- 20170316
LR  - 20171116
IS  - 1791-244X (Electronic)
IS  - 1107-3756 (Linking)
VI  - 39
IP  - 2
DP  - 2017 Feb
TI  - Wheat-bran autolytic peptides containing a branched-chain amino acid attenuate 
      non-alcoholic steatohepatitis via the suppression of oxidative stress and the 
      upregulation of AMPK/ACC in high-fat diet-fed mice.
PG  - 407-414
LID - 10.3892/ijmm.2016.2831 [doi]
AB  - Whole-wheat intake is known to reduce the risk of metabolic syndrome. However, 
      the active component remains unclear. Recently, we identified bioactive peptides 
      [leucine-arginine-proline (LRP) and leucine-glutamine‑proline (LQP)] from wheat 
      bran autolytic hydrolysate. The present study aimed to investigate the effects of 
      LRP and LQP on non-alcoholic steatohepatitis (NASH) in a mouse model. We also 
      evaluated the effects of these peptides on oxidative stress and on the 
      AMP-activated protein kinase (AMPK) signaling pathway, two major pathogenic 
      factors of NASH. Seven‑week-old male C57BL/6 mice were fed a high-fat diet for 
      10 weeks and administered water supplemented with 0.05% LRP, 0.20% LRP, 
      0.05% LQP, or 0.20% LQP (each n=5) or distilled water (control; n=5) ad libitum. 
      Oxidative stress was evaluated by measuring the serum levels of diacron reactive 
      oxygen metabolite (d-ROM) and biological antioxidant potential (BAP). Hepatic 
      expression of phosphorylated AMPK and phosphorylated acetyl-CoA carboxylase (ACC) 
      were evaluated by immunoblotting. The result showed that non‑alcoholic fatty 
      liver disease activity score was significantly decreased in all types of 
      treatment. Serum d-ROM levels were significantly decreased in the 0.20% LRP 
      group, but not in the 0.05% LRP, 0.05% LQP, and 0.20% LQP groups. Serum BAP 
      levels were significantly increased in the 0.05% LRP and 0.20% LRP groups, but 
      not in the 0.05% LQP and 0.20% LQP groups. Immunoblotting analysis revealed that 
      the expression of phospho-AMPK was increased whereas that of phospho-ACC was 
      decreased in the 0.20% LQP group. In conclusion, we demonstrated that both LRP 
      and LQP alleviated the severity of NASH in a high-fat diet-induced NASH mouse 
      model. In addition, we showed that LRP and LQP modulated oxidative stress and 
      upregulated AMPK/ACC, respectively. Thus, LRP and LQP may constitute clinically 
      applicable therapeutic agents for NASH.
FAU - Kawaguchi, Takumi
AU  - Kawaguchi T
AD  - Division of Gastroenterology, Department of Medicine, Kurume University School of 
      Medicine, Kurume, Japan.
FAU - Ueno, Takato
AU  - Ueno T
AD  - Asakura Medical Association Hospital, Asakura, Japan.
FAU - Nogata, Yoichi
AU  - Nogata Y
AD  - NARO Western Region Agricultural Research Center, Kagawa, Japan.
FAU - Hayakawa, Masako
AU  - Hayakawa M
AD  - Liver Cancer Division, Research Center for Innovative Cancer Therapy, Kurume 
      University, Kurume, Japan.
FAU - Koga, Hironori
AU  - Koga H
AD  - Division of Gastroenterology, Department of Medicine, Kurume University School of 
      Medicine, Kurume, Japan.
FAU - Torimura, Takuji
AU  - Torimura T
AD  - Division of Gastroenterology, Department of Medicine, Kurume University School of 
      Medicine, Kurume, Japan.
LA  - eng
PT  - Journal Article
DEP - 20161214
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 0 (Amino Acids, Branched-Chain)
RN  - 0 (Antioxidants)
RN  - 0 (Peptides)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - EC 6.4.1.2 (Acetyl-CoA Carboxylase)
SB  - IM
MH  - AMP-Activated Protein Kinases/*metabolism
MH  - Acetyl-CoA Carboxylase/*metabolism
MH  - Amino Acids, Branched-Chain/*metabolism
MH  - Animals
MH  - Antioxidants/metabolism
MH  - Body Weight
MH  - Diet, High-Fat/*adverse effects
MH  - Disease Models, Animal
MH  - Liver/metabolism/pathology
MH  - Male
MH  - Mice
MH  - Non-alcoholic Fatty Liver Disease/*etiology/*metabolism/pathology
MH  - *Oxidative Stress
MH  - Peptides/chemistry/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Triticum/chemistry
EDAT- 2016/12/22 06:00
MHDA- 2017/03/17 06:00
CRDT- 2016/12/22 06:00
PHST- 2016/06/27 00:00 [received]
PHST- 2016/12/12 00:00 [accepted]
PHST- 2016/12/22 06:00 [pubmed]
PHST- 2017/03/17 06:00 [medline]
PHST- 2016/12/22 06:00 [entrez]
AID - 10.3892/ijmm.2016.2831 [doi]
PST - ppublish
SO  - Int J Mol Med. 2017 Feb;39(2):407-414. doi: 10.3892/ijmm.2016.2831. Epub 2016 Dec 
      14.