Effects of fenofibrate on hyperlipidemia and postprandial triglyceride metabolism in human apolipoprotein C1 transgenic mice

To study the in vivo role of apolipoprotein (apo) C1 in lipoprotein metabolism, we have generated transgenic mice expressing the human apo C1 gene. Apo C1 is a small 6.6 kDa protein that is primarily synthesized by the liver and is present on chylomicrons, very low density lipoproteins (VLDL) and high density lipoproteins (HDL). In recent years, studies by our group have shown that apo C1 transgenic mice develop hyperlipidemia due to an accumulation of VLDL-sized lipoprotein particles. The underlying metabolic defect in apo C1 transgenic mice is an impaired uptake of VLDL particles by the liver. Although a role for apo C1 in human disease remains to be established, data presented in the current paper show that apo C1 transgenic mice are an instructive model of hyperlipidemia to (i) elucidate possible mechanisms underlying this disorder and (ii) test the activity and mode of action of hypolipidemic drugs.