Loss of wild-type carrier-mediated L-carnitine transport activity in hepatocytes of juvenile visceral steatosis mice
✍ Scribed by Koichi Yokogawa; Masayuki Yonekawa; Ikumi Tamai; Rikiya Ohashi; Yasuaki Tatsumi; Yasuhiko Higashi; Masaaki Nomura; Noriyoshi Hashimoto; Hiroko Nikaido; Jun-ichiro Hayakawa; Jun-ichi Nezu; Asuka Oku; Miyuki Shimane; Ken-ichi Miyamoto; Akira Tsuji
- Book ID
- 102240438
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 109 KB
- Volume
- 30
- Category
- Article
- ISSN
- 0270-9139
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✦ Synopsis
Juvenile visceral steatosis (JVS) mice, which show systemic L-carnitine deficiency, may be an animal model of Reye's syndrome because of its phenotype of fat deposition and mitochondrial abnormalities in the liver. In this study, we compared the characteristics of the L-carnitine transport in isolated hepatocytes from wild-type and JVS mice. The uptake of L-carnitine by wild-type hepatocytes was saturable and the Eadie-Hofstee plot showed 2 distinct components. The apparent Michaelis constant (K m ) and the maximum transport rate (V max ) were 4.6 mol/L and 59.5 pmol/15 min/10 6 cells, respectively, for the high-affinity component, and 404 mol/L and 713 pmol/15 min/10 6 cells, respectively, for the low-affinity component. The high-affinity L-carnitine uptake occurred via an active carriermediated transport mechanism, which is characterized by Na ؉ -, energy-, and pH-dependency. On the other hand, the high-affinity uptake was absent in JVS hepatocytes, and the values of K m and V max for the low-affinity uptake were 475 mol/L and 557 pmol/15 min/10 6 cells, respectively. The hepatic carnitine transport properties in wild-type hepatocytes were similar to those of high-affinity mouse Octn2transfected HEK293 cells. This study suggests that Octn2type carnitine transporter is dysfunctional in hepatocytes of JVS mice. (HEPATOLOGY 1999;30:997-1001.