Abstract 1024: Phospholipid Transfer Protein (PLTP) Deficient Mice Absorb Less Cholesterol
Apolipoprotein B (apoB)-dependent and apoA-I-dependent pathways for cholesterol transport across the small intestine have been described in vivo. Phospholipid transfer protein (PLTP) knockout (KO) mice have significantly lower levels of plasma cholesterol, apoB, and apoA-I. Here, we show that PLTP KO mice absorbed significantly less radiolabeled cholesterol but not triglyceride after multiple feedings of the lipids within 5 days (35%– 45%, P < 0.01, respectively) than WT mice. The transport of the radiolabeled cholesterol into the plasma, small intestine, and liver during this period of time were significantly reduced (57%, 23%, and 35%, P < 0.01, P < 0.05 and P < 0.05, respectively) in PLTP KO mice, compared to WT ones. The absorption of a bolus of radiolabeled cholesterol (short-term) but not triglyceride in PLTP KO mice was also significantly lower than that of wild type (WT) mice (38%, P < 0.01). Also, cholesterol transport to the plasma, small intestine, and liver was significantly lower in PLTP KO mice than that of WT ones (51%, 24%, and 30%, P < 0.01, P < 0.05, and P < 0.05, respectively). Moreover, we found that, compared to WT mice, PLTP KO primary enterocytes secrete significant less cholesterol through apoB- and apoA-I-dependent pathways (51% and 33%, P < 0.01, respectively) and PLTP KO small intestine contains more cholesterol, which may be related to significant reduction of Niemann-Pick C1 like 1 (NPC1L1) (46%, P < 0.01) and HMGCoA reductase (85%, P < 0.01), and significant induction of ATP-binding cassette transporter G5 (ABCG5) (60%, P < 0.01) expressions. Furthermore, PLTP KO primary enterocytes absorb significant less cholesterol than that of control cells (P < 0.01). In conclusion, PLTP KO mouse small intestine secretes less and accumulates more cholesterol, which, in turn, inhibit cholesterol absorption and this may provide another mechanism for the reduction of atherosclerotic lesions in these mice.