Abstract

To test whether lipoprotein lipase or hepatic lipase activities are associated with lipoprotein subclasses, and to assess the effects of dietary manipulations on these associations, enzyme activities were measured in postheparin plasma (75 U heparin/kg) from 43 healthy men who were randomly allocated to a low-fat (24% fat, 60% carbohydrate) and a high-fat (46% fat, 38% carbohydrate) diet for 6 weeks each in a cross-over design. The high-fat diet significantly increased both lipoprotein lipase (+20%, P = 0.02) and hepatic lipase (+8%, P = 0.007) activities. On both diets, hepatic lipase activity was significantly positively correlated (P < 0.01) with plasma apolipoprotein (apo)B concentrations, and with levels of small dense low density lipoprotein (LDL) III, measured by analytic ultracentrifugation as mass of lipoproteins of flotation rate (Sof) 3-5, while lipoprotein lipase activity was inversely associated with levels of LDL III (P < 0.05). Despite the cross-sectional correlations, increased hepatic lipase activity was not significantly correlated with the reduction in LDL III mass observed on the high-fat diet. Rather, changes in hepatic lipase were correlated inversely with changes in small very low density lipoproteins (VLDL) of Sof 20-40, and small intermediate density lipoproteins (VLDL) of Sof 10-16. Moreover, changes in lipoprotein lipase activity were not significantly correlated with changes in small LDL, but were positively associated with changes in small IDL of Sof 10-14, and large LDL I of Sof 7-10. Thus, while increased levels of small dense LDL are associated with a metabolic state characterized by relatively increased hepatic lipase and decreased lipoprotein lipase activity, changes in these enzymes do not appear to be primary determinants of diet-induced changes in levels of this LDL subfraction. On the other hand, increased lipoprotein lipase activity induced by high-fat feeding may contribute to the accumulation in plasma of both large LDL I and small IDL, whereas increased hepatic lipase may promote catabolism or clearance of triglyceride-rich lipoprotein remnants.

Highlights

  • NB concentrations, and with levels of small dense low density lipoprotein (LDL) 111, measured by analytic ultracentrifugation as mass of lipoproteins of flotation rate (Si') 3-5, while lipoprotein lipase activity was inversely associated with levels of LDL 111(P < 0.05)

  • In humans, cross-cultural and observational studies indicate that large LDL particle size is associated with consumption of diets that are higher in saturated fat [49, 56]

  • Large LDL particles are increased in cholesteryl ester content and are strong predictors of atherosclerosis [57]

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Summary

Introduction

N (apo)B concentrations, and with levels of small dense low density lipoprotein (LDL) 111, measured by analytic ultracentrifugation as mass of lipoproteins of flotation rate (Si') 3-5, while lipoprotein lipase activity was inversely associated with levels of LDL 111(P < 0.05). Differences among LDL particles in physical and chemical properties ( 3 , 4), metabolic characteristics [5], oxidative susceptibility [6, 7], carbohydrate content [8], and cellular uptake [9] may be related to differing roles in the development of coronary artery disease (CAD) [10,11,12] Several metabolic factors such as lipoprotein and hepatic lipase and cholesteryl ester transfer protein are involved in the formation of LDL from triglyceride-rich lipoprotein precursors [12,13,14]. Postheparin plasma lipoprotein lipase activities have been positively associated with high density lipoprotein (HDL)cholesterol and negatively with VLDL cholesterol concentrations [18,19,20].

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