RELATIONSHIPS OF PLASMA AND HEPATIC VARIABLES WITH RATES OF PLASMA LOW-DENSITY-LIPOPROTEIN APOLIPOPROTEIN-B METABOLISM IN BABOONS FED LOW-FAT AND HIGH-FAT DIETS

These studies were conducted to determine relationships of plasma low- density lipoprotein (LDL) cholesterol concentrations and hepatic mRNA levels for apolipoprotein (ape) B, LDL receptor, and hepatic hydroxyme thyl glutaryl coenzyme A (HMG CoA) synthase with plasma LDL apo B prod uction and catabolic rates in baboons maintained on a low-cholesterol, low-fat chow diet and on a high cholesterol, high-fat (HCHF) diet. Tw elve baboons with LDL cholesterol levels ranging from low to high on t he HCHF diet but with similar high-density lipoprotein (HDL) cholester ol levels were selected from a colony of selectively bred pedigreed ba boons. LDL apo B turnover and hepatic mRNA concentrations for apo B, L ot. receptor, and HMG CoA synthase were measured on a chow diet and ag ain on a HCHF diet fed for 14 weeks. LDL apo B fractional catabolic ra tes decreased and production rates increased on the HCHF diet. Hepatic mRNA concentrations for apo B were not affected by the HCHF diet. Hep atic LDL receptor and HMG CoA synthase mRNA concentrations decreased o n the HCHF diet as compared with the chow diet. LDL apo B fractional c atabolic rate was negatively correlated with plasma cholesterol, LDL c holesterol, Lot. apo B, and LDL apo a production and positively correl ated with hepatic LDL receptor and HMG CoA synthase mRNA concentration s and with plasma LDL triglyceride to cholesterol ratio on the chow di et but not on the HCHF diet. LDL apo B production was positively corre lated with plasma cholesterol, LDL cholesterol, and LDL apo B on the H CHF diet and negatively correlated with LDL triglyceride to cholestero l ratio on both chow and HCHF diets. Hepatic apo a mRNA concentrations were not correlated with either the fractional catabolic rate or prod uction rate on either diet. When baboons were grouped by LDL cholester ol response, high responders had lower LDL apo B fractional catabolic rate and lower hepatic LDL receptor mRNA on the chow diet as compared with those having no or moderate response. On the other hand, high res ponders had high LDL apo B production on the HCHF diet as compared wit h those having no or moderate response. These results suggest that Lot . catabolism regulates LDL cholesterol in plasma on the chow diet, and that hepatic LDL receptor mRNA concentrations are associated with LDL catabolic rate. However, LDL apo B production is the major determinan t of LDL cholesterol in the plasma on a HCHF diet, and production of L DL apo B is not associated with hepatic apo a mRNA concentrations. Cop yright (C) 1995 by W.B. Saunders Company