Prevention of free fatty acid-induced hepatic lipotoxicity by carnitine via reversal of mitochondrial dysfunction.
Liver Int
; 31(9): 1315-24, 2011 Oct.
Article
em En
| MEDLINE
| ID: mdl-22093454
ABSTRACT
BACKGROUND:
Mitochondria are the main sites for fatty acid oxidation and play a central role in lipotoxicity and nonalcoholic steatohepatitis.AIMS:
We investigated whether carnitine prevents free fatty acid (FFA)-induced lipotoxicity in vitro and in vivo.METHODS:
HepG2 cells were incubated with FFA, along with carnitine and carnitine complexes. Mitochondrial ß-oxidation, transmembrane potential, intracellular ATP levels and changes in mitochondrial copy number and morphology were analysed. Otsuka Long-Evans Tokushima Fatty and Long-Evans Tokushima Otsuka rats were segregated into three experimental groups and fed for 8 weeks with (i) normal chow, (ii) a methionine choline-deficient (MCD) diet or (iii) an L-carnitine-supplemented MCD diet.RESULTS:
Carnitine prevented FFA-induced apoptosis (16% vs. 3%, P < 0.05). FFA treatment resulted in swollen mitochondria with increased inner matrix density and loss of cristae. However, mitochondria co-treated with carnitine had normal ultrastructure. The mitochondrial DNA copy number was higher in the carnitine treatment group than in the palmitic acid treatment group (375 vs. 221 copies, P < 0.05). The carnitine group showed higher mitochondrial ß-oxidation than did the control and palmitic acid treatment groups (597 vs. 432 and 395 ccpm, P < 0.05). Carnitine treatment increased the mRNA expression of carnitine palmitoyltransferase 1A and peroxisome proliferator-activated receptor-γ, and carnitine-lipoic acid further augmented the mRNA expression. In the in vivo model, carnitine-treated rats showed lower alanine transaminase levels and lesser lobular inflammation than did the MCD-treated rats.CONCLUSIONS:
Carnitine and carnitine-lipoic acid prevent lipotoxicity by increasing mitochondrial ß-oxidation and reducing intracellular oxidative stress.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Mitocôndrias Hepáticas
/
Carnitina
/
Ácido Tióctico
/
Ácidos Graxos não Esterificados
/
Fígado Gorduroso
/
Fígado
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article