Reduced high density lipoprotein cholesterol in severe hypertriglyceridemic ApoCIII transgenic mice via lowered hepatic ApoAI synthesis

Clinical and epidemiological investigations confirm that patients with loss-of-function mutations (R19X, etc.) in Apolipoprotein CIII (ApoCIII) showed beneficial lipid profile including decreased plasma triglyceride and increased high density lipoprotein (HDL) levels. However, whether HDL level would be reduced in hypertriglyceridemia (HTG) induced by high ApoCIII expression has not been demonstrated yet. Here we showed, ApoCIII transgenic mice (ApoCIIItg) displayed severe HTG and had significantly lower HDL level. Analysis of apolipoproteins in lipoprotein fractions by SDS-PAGE revealed marked decrease of apolipoprotein AI (ApoAI) in HDL in transgenic mice compared with the wild type mice (WT) as controls. Further examination demonstrated that hepatic but not intestinal ApoAI mRNA was significantly reduced. Therefore, the decreased ApoAI synthesis might be accounted for the lower plasma HDL level in ApoCIII transgenic mice.