CHYLOMICRON-SIZED LIPID PARTICLES ARE FORMED IN THE SETTING OF APOLIPOPROTEIN-B DEFICIENCY

The mechanisms for packaging large quantities of neutral lipids into a polipoprotein (apo) B-containing lipoproteins (chylomicrons or VLDL) a re incompletely understood, However, several lines of evidence have su ggested that the addition of core lipids to apoB to form a lipoprotein particle within the endoplasmic reticulum (ER) may involve two steps: first, the addition of small amounts of core lipids to membrane-bound apoB, generating a lipid-poor, small apoB-containing particle, and se cond, the fusion of that particle with a larger, independently formed triglyceride-rich and apoB-free ''lipid particle.'' We sought to test this two-step hypothesis of apoB core lipidation by using electron mic roscopy to compare chylomicron assembly in mice that are genetically d eficient in the ability to synthesize apoB in the intestine to control mice, In 19-day gestational mice (fasting setting) that were deficien t in intestinal apoB synthesis, chylomicron-sized Lipid particles in t he lumen of the enterocyte ER were even more abundant and were 2- to 3 -fold larger than those in the enterocytes of normal control mice, How ever, there were fewer lipid-staining particles ha the Golgi apparatus , and many fewer particles in the extracellular space, compared with n ormal control mice. In both types of newborn suckling mice, much large r lipid particles were assembled within the lumen of the ER, They were however, less abundant and rarely reached the Golgi apparatus in fatt y enterocytes of intestines deficient in apoB synthesis. These observa tions provide in vivo evidence that chylomicron formation could involv e the synthesis of apoB-free triglyceride-rich particles within the en doplasmic reticulum (ER) lumen, and that the transport of these li:pid particles out of the ER to Golgi apparatus and interstitium is facili tated by the acquisition of apoB.