PMID- 23669346
OWN - NLM
STAT- MEDLINE
DCOM- 20130923
LR  - 20171116
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1832
IP  - 10
DP  - 2013 Oct
TI  - Ketogenic essential amino acids replacement diet ameliorated hepatosteatosis with 
      altering autophagy-associated molecules.
PG  - 1605-12
LID - S0925-4439(13)00157-9 [pii]
LID - 10.1016/j.bbadis.2013.05.003 [doi]
AB  - Ketogenic amino acid (KAA) replacement diet has been shown to cure hepatic 
      steatosis, a serious liver disease associated with diverse metabolic defects. In 
      this study, we investigated the effects of KAA replacement diet on nutrition 
      sensing signaling pathway and analyzed whether induction of hepatic autophagy was 
      involved. Mice are fed with high fat diet (HFD) or KAA replacement in high-fat 
      diet (30% fat in food; HFD)-fed (HFD(KAAR)) and sacrificed at 8, 12, 16 weeks 
      after initiation of experimental food. Hepatic autophagy was analyzed in protein 
      expression of several autophagy-associated molecules and in light chain-3 green 
      fluorescent protein (LC-3 GFP) transgenic mice. HFD(KAAR) showed increased 
      AMP-activated protein kinase (AMPK) phosphorylation and enhanced liver kinase B1 
      (LKB1) expression compared to control HFD-fed mice. The KAA-HFD-induced 
      activation of AMPK was associated with an increased protein expression of sirtuin 
      1 (Sirt1), decreased forkhead box protein O3a (Foxo3a) level, and suppression of 
      mammalian target of rapamycin (mTOR) phosphorylation compared with the HFD-fed 
      mice. The intervention study revealed that a KAA-replacement diet also 
      ameliorated all the established metabolic and autophagy defects in the HFD-fed 
      mice, suggesting that a KAA-replacement diet can be used therapeutically in 
      established diseases. These results indicate that KAA replacement in food could 
      be a novel strategy to combat hepatic steatosis and metabolic abnormalities 
      likely involvement of an induction of autophagy.
CI  - Copyright (c) 2013 Elsevier B.V. All rights reserved.
FAU - Xu, Ling
AU  - Xu L
AD  - Kanazawa Medical University, Uchinada, Ishikawa, Japan.
FAU - Kanasaki, Megumi
AU  - Kanasaki M
FAU - He, Jianhua
AU  - He J
FAU - Kitada, Munehiro
AU  - Kitada M
FAU - Nagao, Kenji
AU  - Nagao K
FAU - Jinzu, Hiroko
AU  - Jinzu H
FAU - Noguchi, Yasushi
AU  - Noguchi Y
FAU - Maegawa, Hiroshi
AU  - Maegawa H
FAU - Kanasaki, Keizo
AU  - Kanasaki K
FAU - Koya, Daisuke
AU  - Koya D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130511
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Amino Acids, Essential)
RN  - 0 (Dietary Fats)
SB  - IM
MH  - Amino Acids, Essential/*administration & dosage
MH  - Animals
MH  - *Autophagy
MH  - Body Weight
MH  - *Diet, Ketogenic
MH  - Dietary Fats/administration & dosage
MH  - Fatty Liver/*diet therapy
MH  - Macrophages/physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Organ Size
OTO - NOTNLM
OT  - AMPK
OT  - Amino acid
OT  - Atg
OT  - Autophagy
OT  - Fatty liver
OT  - Foxo
OT  - HFD
OT  - KAA
OT  - LC-3
OT  - LKB1
OT  - Metabolic syndrome
OT  - Nutritional intervention
OT  - Obesity
OT  - adenine monophosphate-activated protein kinase
OT  - autophagy-related protein
OT  - forkhead homeobox type O
OT  - high fat diet
OT  - ketogenic amino acids
OT  - light chain-3
OT  - liver kinase B1
OT  - mTOR
OT  - mammalian target of rapamycin
EDAT- 2013/05/15 06:00
MHDA- 2013/09/24 06:00
CRDT- 2013/05/15 06:00
PHST- 2013/01/22 00:00 [received]
PHST- 2013/05/03 00:00 [revised]
PHST- 2013/05/06 00:00 [accepted]
PHST- 2013/05/15 06:00 [entrez]
PHST- 2013/05/15 06:00 [pubmed]
PHST- 2013/09/24 06:00 [medline]
AID - S0925-4439(13)00157-9 [pii]
AID - 10.1016/j.bbadis.2013.05.003 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2013 Oct;1832(10):1605-12. doi: 
      10.1016/j.bbadis.2013.05.003. Epub 2013 May 11.