Circulating Lipoprotein Profiles are Modulated Differently by Lipoprotein Lipase in Obese Humans

Abstract

Background

Several genetic analyses have suggested that lipoprotein lipase (LpL) genotypes causing decreased LpL activity correlate with increased triglyceride concentrations and risk for coronary artery disease. In contrast, in some other studies LpL activity was positively correlated with plasma low-density lipoprotein (LDL) cholesterol concentrations.

Objective

To assess whether these different associations represent physiologic differences in lipoprotein metabolism.

Methods

We correlated postheparin lipase activities, postprandial lipemia, and fasting lipoprotein concentrations in obese (BMI ≥ 30 kg/m², n = 26) and non-obese (BMI ≤ 30 kg/m², n = 57) individuals. LpL was measured using specific inhibitory antibodies.

Results

Surprisingly, LpL activity was significantly correlated with triglyceride area under the curve after a fat load in the non-obese, but not the entire group. Moreover, in non-obese individuals, LpL activity correlated directly (r= 0.40) and hepatic lipase activity correlated inversely (r = −0.32) with high-density lipoprotein (HDL) cholesterol concentrations. These relationships were not found in the obese group, in whom LpL correlated with LDL cholesterol concentrations (r = 0.54).

Conclusions

We conclude that postheparin LpL activity relates to different lipoproteins in obese and non-obese individuals. In obesity, greater LpL activity may enhance conversion of very-low-density lipoprotein cholesterol to LDL cholesterol, whereas in non-obese individuals the correlation is with HDL cholesterol. Whether this is due to differences in the source of LpL (muscle or fat), or to other associated alterations in lipoprotein metabolism is unknown. These results may explain the non-uniformity of correlations between LpL and atherogenic lipoproteins in different populations.