Prevention of free fatty acid-induced hepatic lipotoxicity by carnitine via reversal of mitochondrial dysfunction

Title
Prevention of free fatty acid-induced hepatic lipotoxicity by carnitine via reversal of mitochondrial dysfunction
Author
최호순
Keywords
carnitine; lipotoxicity; mitochondria
Issue Date
2011-12
Publisher
Blackwell Publishing Ltd
Citation
Liver International, 2011, 31(9), P.1315-1324
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 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.
URI
https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1478-3231.2011.02602.xhttp://hdl.handle.net/20.500.11754/65597
ISSN
1478-3223
DOI
10.1111/j.1478-3231.2011.02602.x
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COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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