Effect of combined lipase deficiency (cld/cld) on hepatic and lipoprotein lipase activities in liver and plasma of newborn mice.

Combined lipase deficiency (cld/cld) is a recessive mutation in mice which results in massive hyperlipemia and death within 3 days after birth. We studied the effect of this deficiency on lipolytic activities in liver and in pre- and postheparin plasma of mice less than 2 days old. Anti-hepatic lipase serum inhibited more than 85% of the lipolytic activity in liver and plasma of normal newborn mice when assayed in high-salt medium, validating the use of this medium for measuring hepatic lipase activity in mice. Anti-lipoprotein lipase serum, in contrast, inhibited only two-thirds of the lipolytic activity in liver and plasma when assayed in serum low-salt medium, and anti-hepatic lipase serum inhibited the rest. This indicates that assay with serum low-salt medium alone is not specific for lipoprotein lipase activity in mice. Therefore, immunoinhibition was used, as needed, for measuring lipoprotein lipase activity. The livers of unaffected newborn mice contained high levels of both hepatic and lipoprotein lipase activities, 228 and 187 mU/g, respectively. The plasma of unaffected mice contained a high level of hepatic lipase activity, 244 mU/ml, but practically no lipoprotein lipase activity. Heparin injected intraperitoneally increased plasma lipoprotein lipase activity to 152 mU/ml, but had no effect on plasma hepatic lipase activity, in unaffected mice. Hepatic lipase activity was virtually absent from both liver and plasma of cld/cld mice. Lipoprotein lipase activity was present in the liver at a surprisingly high level, 40% of that in normals, but was barely detectable in plasma. Heparin injection increased plasma lipoprotein lipase activity in cld/cld mice, but the increment was less than 10% of that in unaffected mice. Heparin had no significant effect on plasma hepatic lipase activity in defective mice. These findings confirm preliminary observations that hepatic lipase activity in liver and plasma and lipoprotein lipase activity in plasma are markedly reduced in combined lipase deficiency. The unexpected high level of lipoprotein lipase activity in liver of cld/cld mice suggests that regulation of lipoprotein lipase activity in liver of neonatal mice is different from that in other tissues.