The unique inborn
hypertriglyceridemia seen in FLS (
fatty liver Shionogi) mice was relieved by the administration of purified
apolipoprotein (
apo) C-II.
Lipoprotein lipase (LPL) and its cofactor,
apoC-II, play a pivotal role in VLDL metabolism. Therefore, we investigated the genetic background involved in this
hypertriglyceridemia. Plasma levels of TG and total
cholesterol as well as LPL activity were measured in male FLS mice and C57/BL6J mice.
Agarose gel electrophoresis and fast
protein liquid chromatography were used to analyze the
lipoprotein profile. A cross experiment was done to determine the genetic background of
hypertriglyceridemia observed in FLS mice.
cDNA sequences of
apoC-II and
apoC-III of FLS mice were determined. Prealpha-
lipoprotein was the predominant
lipoprotein class in FLS mouse plasma. LPL activity remained in the range observed in C57/BL6J mice, and purified
apoC-II transiently relieved FLS mice from
hypertriglyceridemia. Prealpha-lipoproteinemia was inherited in an autosomal recessive manner.
ApoC-III appeared to be a causal factor for this unique
hypertriglyceridemia. Microsatellite analysis, however, revealed that the responsible chromosome was not 7; rather,
apoC-III mapped onto chromosome 9. Therefore, we suggest
apoC-III as a candidate causative factor for the
hypertriglyceridemia observed in FLS mice because an excessive amount of
apoC-III attenuates LPL activity in vivo and in vitro.