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

• Published in: Liver international 2011-10, Vol.31 (9), p.1315-1324
• Main Authors: Jun, Dae Won, Cho, Won Kyeong, Jun, Jin Hyun, Kwon, Hyuk Jin, Jang, Ki-Seok, Kim, Hyun-Jeong, Jeon, Hye Jun, Lee, Kang Nyeong, Lee, Hang Lak, Lee, Oh Young, Yoon, Byung Chul, Choi, Ho Soon, Hahm, Joon Soo, Lee, Min Ho
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - metabolism; Animals; Apoptosis - drug effects; carnitine; Carnitine - analogs & derivatives; Carnitine - pharmacology; Carnitine O-Palmitoyltransferase - genetics; Carnitine O-Palmitoyltransferase - metabolism; Choline Deficiency - complications; Disease Models, Animal; DNA, Mitochondrial - metabolism; Fatty Acids, Nonesterified - metabolism; Fatty Liver - etiology; Fatty Liver - genetics; Fatty Liver - metabolism; Fatty Liver - pathology; Fatty Liver - prevention & control; Gene Expression Regulation - drug effects; Hep G2 Cells; Humans; lipotoxicity; Liver - drug effects; Liver - metabolism; Liver - pathology; Lysosomes - drug effects; Lysosomes - metabolism; Membrane Potential, Mitochondrial - drug effects; Methionine - deficiency; mitochondria; Mitochondria, Liver - drug effects; Mitochondria, Liver - metabolism; Mitochondria, Liver - pathology; Non-alcoholic Fatty Liver Disease; Oxidation-Reduction; Oxidative Stress - drug effects; PPAR gamma - genetics; PPAR gamma - metabolism; Rats; Rats, Inbred OLETF; Rats, Long-Evans; RNA, Messenger - metabolism; Thioctic Acid - analogs & derivatives; Thioctic Acid - pharmacology; Time Factors
• ISSN: 1478-3223; 1478-3231
• DOI: 10.1111/j.1478-3231.2011.02602.x

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