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Requirement of cholesterol for secretion of the very low density lipoprotein (VLDL) by the rat liver

Conference · · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:6326544
Fatty acids stimulate hepatic secretion of VLDL triglyceride (TG) and cholesterol (C), increase C synthesis, and enhance activity of HMG-CoA reductase. Livers from normal fed male rats were perfused for 4 hr in a medium containing 20..mu..Ci (2-/sup 14/C) acetate, 6g/dl serum albumin, 300 mg/dl glucose in Krebs-Henseleit HCO/sub 3/ buffer (pH 7.4), 0-100 ..mu..g/ml mevinolin, and oleate. TG secretion was decreased 0%, 23%, and 32% from control with 1, 10, and 100 ..mu..g/ml mevinolin, respectively; there was no significant effect on C or C ester (CE) secretion. Specific activity (dpm/..mu..mol) of C synthesized from acetate in the liver decreased 67%, 98%, and 99% from control; incorporation into CE decreased 64%, 81%, and 84%, respectively. TG and phospholipid (PL) activities did not change. Synthesis of TG and PL from (1-/sup 14/C) oleate by isolated hepatocytes from normal fed rats was not affected by addition of 0-100 ..mu..g/ml mevinolin. The mass of C and TG in the liver did not change. Preliminary experiments with perfused liver suggest that output of VLDL TG, C, CE, and PL was diminished; the ratio of C/TG and PL/TG in the VLDL was constant, suggesting secretion of fewer VLDL particles with the same composition. These data suggest that mevinolin acutely reduces biosynthesis of C and secretion of the VLDL, presumably because of a requirement of C for synthesis and secretion of the VLDL.
Research Organization:
Univ. of Tennessee, Memphis
OSTI ID:
6326544
Report Number(s):
CONF-870644-
Conference Information:
Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 46:6
Country of Publication:
United States
Language:
English