Hepatocyte ABCA1 deficiency is associated with reduced HDL sphingolipids

ATP binding cassette transporter A1 (ABCA1) limits the formation of high density lipoproteins (HDL) as genetic loss ABCA1 function causes virtual HDL deficiency in patients with Tangier disease. Mice a hepatocyte-specific knockout (Abca1 HSKO) have 20% wild type (WT) plasma HDL-cholesterol levels, suggesting major contribution hepatic to phenotype. Whether sphingolipids are reduced disease and what extent contributes sphingolipid (SL) levels is unknown. Here, we report drastic reduction total SL patient compound heterozygosity for mutations ABCA1. Compared mutation-free controls, heterozygous had no significant effect on SLs plasma; however, apoB-depleted showed also het carriers. Similarly, liver specific Abca1 KO mice liver. In parallel, apoM sphingosine-1-phosphate (S1P) were HSKO mice. Primary hepatocytes from modest, but concentration compared WT hepatocytes, although de novo synthesis secretion slightly increased hepatocytes. We conclude that signficant contributor maintaining pool sphingolipids, including sphingomyelins S1P.