Relationships of plasma and hepatic variables with rates of plasma low-density lipoprotein apolipoprotein B metabolism in baboons fed low- and high-fat diets

Abstract

These studies were conducted to determine relationships of plasma low-density lipoprotein (LDL) cholesterol concentrations and hepatic mRNA levels for apolipoprotein (apo) B, LDL receptor, and hepatic hydroxymethyl glutaryl coenzyme A (HMG CoA) synthase with plasma LDL apo B production and catabolic rates in baboons maintained on a low-cholesterol, low-fat chow diet and on a high-cholesterol, high-fat (HCHF) diet. Twelve baboons with LDL cholesterol levels ranging from low to high on the HCHF diet but with similar high-density lipoprotein (HDL) cholesterol levels were selected from a colony of selectively bred pedigreed baboons. LDL apo B turnover and hepatic mRNA concentrations for apo B, LDL receptor, and HMG CoA synthase were measured on a chow diet and again on a HCHF diet fed for 14 weeks. LDL apo B fractional catabolic rates decreased and production rates increased on the HCHF diet. Hepatic mRNA concentrations for apo B were not affected by the HCHF diet. Hepatic LDL receptor and HMG CoA synthase mRNA concentrations decreased on the HCHF diet as compared with the chow diet. LDL apo B fractional catabolic rate was negatively correlated with plasma cholesterol, LDL cholesterol, LDL apo B, and LDL apo B production and positively correlated with hepatic LDL receptor and HMG CoA synthase mRNA concentrations and with plasma LDL triglyceride to cholesterol ratio on the chow diet but not on the HCHF diet. LDL apo B production was positively correlated with plasma cholesterol, LDL cholesterol, and LDL apo B on the HCHF diet and negatively correlated with LDL triglyceride to cholesterol ratio on both chow and HCHF diets. Hepatic apo B mRNA concentrations were not correlated with either the fractional catabolic rate or production rate on either diet. When baboons were grouped by LDL cholesterol 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 responders had high LDL apo B production on the HCHF diet as compared with those having no or moderate response. These results suggest that LDL 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 determinant of LDL cholesterol in the plasma on a HCHF diet, and production of LDL apo B is not associated with hepatic apo B mRNA concentrations.