RELATIONSHIP BETWEEN LIPOPROTEIN-LIPASE AND HIGH-DENSITY-LIPOPROTEIN CHOLESTEROL IN MICE - MODULATION BY CHOLESTERYL ESTER TRANSFER PROTEINAND DIETARY STATUS

Plasma lipoprotein lipase (LPL) activity correlates with high density lipoprotein (HDL) cholesterol levels in humans. However, in several mo use models created either through transgenesis or targeted inactivatio n of LPL, no significant changes in HDL cholesterol values have been e vident. One possible explanation for this species difference could be the absence of plasma cholesteryl ester transfer protein (CETP) activi ty in mice. To explore this possibility and further investigate intera ctions between LPL and CETP modulating HDL cholesterol levels in vivo, we examined the relationship between LPL activity and HDL levels in m ice expressing the simian CETP transgene, compared with littermates no t carrying the CETP gene. On a chow diet, increasing LPL activity was associated with a trend towards increased HDL levels (51 +/- 29 vs. 31 +/- 4 mg/dL highest vs. lowest tertiles of LPL activity, P = 0.07) in mice expressing CETP, while no such effects were seen in the absence of CETP (65 +/- 12 vs. 61 +/- 15 mg/dL). Furthermore, in the presence of CETP, a significant positive correlation between LPL activity and H DL cholesterol was evident (r = 0.15, P = 0.006), while in the absence of CETP no such correlation was detected (r = 0.15, P = 0.36), highli ghting the interactions between LPL and CETP in vivo. When mice were c hallenged with a high fat, high carbohydrate diet, strong correlations between LPL activity and HDL cholesterol were seen in both the presen ce (r = 0.45, P = 0.03) and absence (r = 0.73, P < 0.001) of CETP. The refore, under altered metabolic contexts, such as those induced by die tary challenge, the relation between LPL activity and HDL cholesterol may also become evident. Here we have shown that both genetic and envi ronmental factors may modulate association between LPL activity and HD L cholesterol, and provide explanations for the absence of any changes in HDL values in mice either transgenic or with targeted disruption o f the LPL gene.