Loss of wild-type carrier-mediated L-carnitine transport activity in hepatocytes of juvenile visceral steatosis mice

Hepatology. 1999 Oct;30(4):997-1001. doi: 10.1002/hep.510300423.

Abstract

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 micromol/L and 59.5 pmol/15 min/10(6) cells, respectively, for the high-affinity component, and 404 micromol/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 carrier-mediated 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 micromol/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 Octn2-transfected HEK293 cells. This study suggests that Octn2-type carnitine transporter is dysfunctional in hepatocytes of JVS mice.

MeSH terms

  • 2,4-Dinitrophenol / pharmacology
  • Animals
  • Anions / pharmacology
  • Biological Transport
  • Carnitine / pharmacokinetics
  • Carrier Proteins / metabolism*
  • Cations / pharmacology
  • Fatty Liver / metabolism*
  • Hydrogen-Ion Concentration
  • Liver / metabolism*
  • Liver / pathology
  • Male
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Organic Cation Transport Proteins*
  • Reference Values
  • Sodium / pharmacology
  • Sodium Azide / pharmacology
  • Solute Carrier Family 22 Member 5

Substances

  • Anions
  • Carrier Proteins
  • Cations
  • Membrane Proteins
  • Organic Cation Transport Proteins
  • SLC22A5 protein, human
  • Solute Carrier Family 22 Member 5
  • Sodium Azide
  • Sodium
  • 2,4-Dinitrophenol
  • Carnitine