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, while 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. Nicodinamide adenine dinucleotide levels and sirtuin 1 expression, as well as endothelial nitric oxide (eNOS) and mammalian/mechanistic target of rapamycin (mTOR) signaling pathways, were down-regulated 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.
A specific amino acid formula prevents alcoholic liver disease in rodents / L. Tedesco, G. Corsetti, C. Ruocco, M. Ragni, F. Rossi, M.O. Carruba, A. Valerio, E. Nisoli. - In: AMERICAN JOURNAL OF PHYSIOLOGY: GASTROINTESTINAL AND LIVER PHYSIOLOGY. - ISSN 0193-1857. - 314:5(2018 May), pp. G566-G582.
|Titolo:||A specific amino acid formula prevents alcoholic liver disease in rodents|
NISOLI, ENZO (Corresponding)
|Parole Chiave:||alcoholic liver disease; branched-chain amino acids; endothelial nitric oxide synthase; mechanistic target of rapamycin; mitochondrial biogenesis|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||mag-2018|
|Data ahead of print / Data di stampa:||25-gen-2018|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1152/ajpgi.00231.2017|
|Appare nelle tipologie:||01 - Articolo su periodico|