Lipoprotein lipase and hepatic lipase deficiencies associated with impaired chylomicron clearance in D-(+) galactosamine hepatitis.
D-(+) galactosamine (GaIN) produces a reversible from of hepatic injury in the rat, accompanied by alterations in morphology and composition of plasma lipoproteins in the fasting state. Lipoprotein lipase (LPL) and hepatic lipase (HL) activities were measured in fasting control and GaIN rats 24 hr after GaIN injection and initiation of fasting. Significant (p less than 0.001) deficiencies of both enzymes were noted in GaIN animals as compared to controls with LPL activity decreasing to 37.6% and HL activity to 23.2% of control values in GaIN animals. Serial enzyme determinations performed in both GaIN and control animals after gastric fat loading revealed an early persistent HL deficiency (p less than 0.025) at 9 hr after GaIN injection and initiation of fasting which persisted after the fat loading at 15 hr, and a later appearing LPL deficiency (p less than 0.025) was noted at 24 hr after GaIN injection and at 9 hr after fat loading. Serial compositional studies of plasma lipoproteins in pooled specimens after a gastric fat load revealed a marked chylomicronemia in GaIN animals compared to controls which reached a maximum at 12 hr after fat loading. A slight increase in VLDL (very low density lipoprotein) triglyceride and total cholesterol (CH) and a late-appearing (16 hr after fat loading) LDL (low density lipoprotein) CH peak, consisting mostly of unesterified CH, were also noted in GaIN rats as compared to control animals. These data demonstrate a defect in chylomicron (CM) catabolism in GaIN hepatopathy in the rat which is probably secondary to the observed severe LPL and HL deficiencies, although other factors such as activator deficiency, plasma inhibitory substances, and a defective CM particle may be important.
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology*; D002914:Chylomicrons / Q000378:metabolism*; D004041:Dietary Fats / Q000494:pharmacology; D005215:Fasting; D005260:Female; D005688:Galactosamine; D008049:Lipase / Q000097:blood*; D008071:Lipoprotein Lipase / Q000097:blood*; D008074:Lipoproteins / Q000097:blood; D008099:Liver / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains
D002914:Chylomicrons; D004041:Dietary Fats; D008074:Lipoproteins; D005688:Galactosamine; D008049:Lipase; D008071:Lipoprotein Lipase