최호순
2018-04-11T14:47:22Z
2018-04-11T14:47:22Z
2011-12
Liver International, 2011, 31(9), P.1315-1324
1478-3223
https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1478-3231.2011.02602.x
http://hdl.handle.net/20.500.11754/65597
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 β-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 β-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 β-oxidation and reducing intracellular oxidative stress.
en
Blackwell Publishing Ltd
carnitine
lipotoxicity
mitochondria
Prevention of free fatty acid-induced hepatic lipotoxicity by carnitine via reversal of mitochondrial dysfunction
Article
9
31
10.1111/j.1478-3231.2011.02602.x
1315-1324
LIVER INTERNATIONAL
JunJun, D. W.Cho, W. K.Jun, J. H.Kwon, H. J.Jang, K. S.Kim, H. J.Jeon, H. J.Lee, K. N.Lee, H. L.Lee, O. Y. D. W.
Cho, W. K.
Jun, J. H.
Kwon, H. J.
Jang, K. S.
Kim, H. J.
Jeon, H. J.
Lee, K. N.
Lee, H. L.
Lee, O. Y.
2011211589
S
COLLEGE OF MEDICINE[S]
DEPARTMENT OF MEDICINE
hschoi96