Chylomicron and very low-density lipoprotein apolipoprotein B metabolism: mechanism of the response to stanozolol in a patient with severe hypertriglyceridemia.
Studies of simultaneous autologous 131I-chylomicron (Sf greater than 400) and 125I-very low density lipoprotein (VLDL) (Sf 20 to 400) apolipoprotein B (apo B) were performed both before (triglyceride level c 1500 mg/dL) and during treatment with stanozolol, a 17 alpha-methyl anabolic androgenic steroid (triglyceride level c 750 mg/dL) in a 74-year-old woman with a past history of recurrent chylomicronemic pancreatitis. Both before and during stanozolol treatment chylomicron apo B disappeared rapidly and directly, little appearing in VLDL and virtually none in intermediate (IDL) or low density lipoproteins (LDL). Multicompartmental analysis indicated that the great majority of chylomicron apo B was removed via an extremely rapid compartment (estimated fractional catabolic rate [FCR], 5.0/h), accounting for 66% before and 88% during stanozolol treatment. The remaining 131I-apo B decayed biphasically, with total Sf greater than 400 residence times of 8.6 hours before and 3.7 hours during stanozolol treatment. Hence, despite a moderately depressed adipose tissue lipoprotein lipase activity, the subject's hypertriglyceridemia did not appear to proceed solely from retarded chylomicron removal, nor was the dramatic decrease in triglyceride in response to stanozolol a function only of the acceleration of such removal. VLDL apo B kinetics were analyzed by a multicompartmental model featuring a rapid, stepwise delipidation chain which proceeds either rapidly to IDL and LDL or to a slowly turning over compartment within VLDL. While VLDL. apo B synthesis remained essentially constant, the major effect of stanozolol was a substantial reduction in the fraction of VLDL apo B diverted to this slowly turning over compartment, which decreased from 5.0% before to 1.2% during treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
D000368:Aged; D001055:Apolipoproteins B / Q000097:blood*; D002914:Chylomicrons / Q000097:blood*; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood* / Q000188:drug therapy / Q000209:etiology; D007700:Kinetics; D008049:Lipase / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood*; D010195:Pancreatitis / Q000097:blood / Q000150:complications; D013197:Stanozolol / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood*
D001055:Apolipoproteins B; D002914:Chylomicrons; D005938:Glucocorticoids; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D013197:Stanozolol; D008049:Lipase