PMID- 29368944
OWN - NLM
STAT- MEDLINE
DCOM- 20190703
LR  - 20190703
IS  - 1522-1547 (Electronic)
IS  - 0193-1857 (Linking)
VI  - 314
IP  - 5
DP  - 2018 May 1
TI  - A specific amino acid formula prevents alcoholic liver disease in rodents.
PG  - G566-G582
LID - 10.1152/ajpgi.00231.2017 [doi]
AB  - Chronic alcohol consumption promotes mitochondrial dysfunction, oxidative stress, 
      defective protein metabolism, and fat accumulation in hepatocytes (liver 
      steatosis). Inadequate amino acid metabolism is worsened by protein malnutrition, 
      frequently present in alcohol-consuming patients, with reduced circulating 
      branched-chain amino acids (BCAAs). Here we asked whether dietary supplementation 
      with a specific amino acid mixture, enriched in BCAAs (BCAAem) and able to 
      promote mitochondrial function in muscle of middle-aged rodents, would prevent 
      mitochondrial dysfunction and liver steatosis in Wistar rats fed on a 
      Lieber-DeCarli ethanol (EtOH)-containing liquid diet. Supplementation of BCAAem, 
      unlike a mixture based on the amino acid profile of casein, abrogated the 
      EtOH-induced fat accumulation, mitochondrial impairment, and oxidative stress in 
      liver. These effects of BCAAem were accompanied by normalization of leucine, 
      arginine, and tryptophan levels, which were reduced in liver of EtOH-consuming 
      rats. Moreover, although the EtOH exposure of HepG2 cells reduced mitochondrial 
      DNA, mitochondrial transcription factors, and respiratory chain proteins, the 
      BCAAem but not casein-derived amino acid supplementation halted this 
      mitochondrial toxicity. Nicotinamide adenine dinucleotide levels and sirtuin 1 
      (Sirt1) expression, as well as endothelial nitric oxide (eNOS) and 
      mammalian/mechanistic target of rapamycin (mTOR) signaling pathways, were 
      downregulated in the EtOH-exposed HepG2 cells. BCAAem reverted these molecular 
      defects and the mitochondrial dysfunction, suggesting that the mitochondrial 
      integrity obtained with the amino acid supplementation could be mediated through 
      a Sirt1-eNOS-mTOR pathway. Thus a dietary activation of the mitochondrial 
      biogenesis and function by a specific amino acid supplement protects against the 
      EtOH toxicity and preserves the liver integrity in mammals. NEW & NOTEWORTHY 
      Dietary supplementation of a specific amino acid formula prevents both fat 
      accumulation and mitochondrial dysfunction in hepatocytes of alcohol-consuming 
      rats. These effects are accompanied also by increased expression of anti-reactive 
      oxygen species genes. The amino acid-protective effects likely reflect activation 
      of sirtuin 1-endothelial nitric oxide synthase-mammalian target of rapamycin 
      pathway able to regulate the cellular energy balance of hepatocytes exposed to 
      chronic, alcoholic damage.
FAU - Tedesco, Laura
AU  - Tedesco L
AD  - Department of Medical Biotechnology and Translational Medicine, Center for Study 
      and Research on Obesity, University of Milan , Milan , Italy.
FAU - Corsetti, Giovanni
AU  - Corsetti G
AD  - Department of Clinical and Experimental Sciences, University of Brescia , Brescia 
      , Italy.
FAU - Ruocco, Chiara
AU  - Ruocco C
AD  - Department of Medical Biotechnology and Translational Medicine, Center for Study 
      and Research on Obesity, University of Milan , Milan , Italy.
FAU - Ragni, Maurizio
AU  - Ragni M
AD  - Department of Medical Biotechnology and Translational Medicine, Center for Study 
      and Research on Obesity, University of Milan , Milan , Italy.
FAU - Rossi, Fabio
AU  - Rossi F
AD  - Department of Medical Biotechnology and Translational Medicine, Center for Study 
      and Research on Obesity, University of Milan , Milan , Italy.
FAU - Carruba, Michele O
AU  - Carruba MO
AD  - Department of Medical Biotechnology and Translational Medicine, Center for Study 
      and Research on Obesity, University of Milan , Milan , Italy.
FAU - Valerio, Alessandra
AU  - Valerio A
AD  - Department of Molecular and Translational Medicine, University of Brescia , 
      Brescia , Italy.
FAU - Nisoli, Enzo
AU  - Nisoli E
AUID- ORCID: 0000-0002-6670-1630
AD  - Department of Medical Biotechnology and Translational Medicine, Center for Study 
      and Research on Obesity, University of Milan , Milan , Italy.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180125
PL  - United States
TA  - Am J Physiol Gastrointest Liver Physiol
JT  - American journal of physiology. Gastrointestinal and liver physiology
JID - 100901227
RN  - 0 (Amino Acids, Branched-Chain)
RN  - 0 (Reactive Oxygen Species)
RN  - 0U46U6E8UK (NAD)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
SB  - IM
MH  - Alcohol Drinking/*adverse effects/metabolism
MH  - *Amino Acids, Branched-Chain/metabolism/pharmacology
MH  - Animals
MH  - Dietary Supplements
MH  - Disease Models, Animal
MH  - Energy Metabolism/physiology
MH  - *Fatty Liver/etiology/metabolism/prevention & control
MH  - Hep G2 Cells
MH  - Hepatocytes/drug effects/metabolism
MH  - Humans
MH  - Liver/metabolism/pathology
MH  - *Mitochondria/drug effects/physiology
MH  - *Mitochondrial Diseases/chemically induced/metabolism/prevention & control
MH  - NAD/metabolism
MH  - Nitric Oxide Synthase Type III/metabolism
MH  - Oxidative Stress/drug effects
MH  - Rats
MH  - Rats, Wistar
MH  - Reactive Oxygen Species/metabolism
OTO - NOTNLM
OT  - alcoholic liver disease
OT  - branched-chain amino acids
OT  - endothelial nitric oxide synthase
OT  - mechanistic target of rapamycin
OT  - mitochondrial biogenesis
EDAT- 2018/01/26 06:00
MHDA- 2019/07/04 06:00
CRDT- 2018/01/26 06:00
PHST- 2018/01/26 06:00 [pubmed]
PHST- 2019/07/04 06:00 [medline]
PHST- 2018/01/26 06:00 [entrez]
AID - 10.1152/ajpgi.00231.2017 [doi]
PST - ppublish
SO  - Am J Physiol Gastrointest Liver Physiol. 2018 May 1;314(5):G566-G582. doi: 
      10.1152/ajpgi.00231.2017. Epub 2018 Jan 25.