Critical Factors Involved in Intestinal Chylomicron Assembly

Assembly of intestinal chylomicron particles (lipid-protein complexes) is the fundamental mechanism by which we absorb dietary fat. Two intestinal lipid transporters, Cluster of Differentiation 36 (CD36) and fatty acid-binding protein 1 (FABP1), have been shown to play a role in lipid absorption, however, it remains unclear how knockdown of these proteins bleads to aberrant intestinal chylomicron secretion. In an enterocyte-like cell culture model, Caco-2 cells, we hypothesized that knockdown of CD36 or FABP1 using short-hairpin RNA interference techniques would impair triacylglycerol (TG) and apolipoprotein B (apoB) secretion. Surprisingly, knockdown of these lipid transporters lead to an increase in TG and apoB secretion that was associated with an increase in fatty acid synthase and fatty acid transport protein 4 (FATP4) protein levels. De novo fatty acid synthesis was slightly increased in CD36-, but not FABP1-knockdown Caco-2 cells. This study highlights the importance of fatty acid targeting in regulating chylomicron production.MAS