Activation of the Enzymic Activity of Hepatic Lipase by Apolipoprotein A‐II

Human post‐heparin plasma contains two major lipases, lipoprotein lipase and hepatic lipase. Lipoprotein lipase has been investigated extensively and in the presence of a specific activator, apolipoprotein C‐II, is of major importance in modulating the hydrolysis of triacylglycerol rich lipoprotein particles in plasma. The metabolic function and regulation of hepatic lipase is less well established. We have reported previously that apolipoprotein A‐II(apoA‐II) in vitro increased the activity of hepatic lipase by 3.6‐fold [Jahn et al. (1981) FEBS Lett. 131 , 366–368]. We have extended these studies and report here the effects of normal plasma, very low density, low density and high density lipoproteins (VLDL, LDL and HDL) and apolipoproteins A‐I, A‐II, C‐I, C‐II and C‐III on hepatic lipase enzymic activity. Normal plasma and HDL activated hepatic lipase by 255 ± 53% (n = 9) and 288 ± 55% (n = 7) respectively, whereas VLDL inhibited hepatic lipase to 25% and LDL did not affect hepatic lipase enzymic activity (n = 7). Isolated apoA‐I, apoC‐I, apoC‐II, and apoC‐III inhibited hepatic lipase enzymic activity to 25 ± 8% (n = 5), 25 ± 15% (n = 5), 23 ± 7% (n = 5) and 13 ± 10% (n = 5) of the basal level. ApoA‐II recombined with HDL lipids activated by 273 ± 42% (n = 5) whereas apoC‐III recombined with HDL lipids inhibited hepatic lipase to 30% of basal activity. Activation of hepatic lipase by apoA‐II was dependent on temperature and pH, with maximal activation (5.75‐fold over basal levels) occurring at pH 7.5 and 37°C. The addition of lipid‐free apoA‐II 10 min after the hydrolysis of triacylglycerol by hepatic lipase had begun resulted in an increase in rate from 1.9 nmol min −1 ml −1 to 7.0 nmol min −1 ml −1 . The rate observed by the addition of apoA‐II before the start of the reaction was 9.5 nmol min −1 ml −1 . These results are consistent with the concept that apoA‐II modulates the enzymic activity of hepatic lipase, and may play a role in vivo in the regulation of hepatic lipase activity and HDL lipoprotein metabolism.