title: Human apolipoprotein C-III - a new intrahepatic protein factor promoting assembly and secretion of very low density lipoproteins.
abstract: Apolipoprotein (apo) C-III is a small protein (79 amino acids) and a component of triacylglycerol (TAG)-rich very low density lipoproteins (VLDL) and high density lipoproteins. We have unraveled a new intracellular role of apoCIII in promoting hepatic VLDL(1) (Sf > 100) assembly/secretion under lipid-rich conditions. Feeding apoc3-null mice with a high fat diet for two weeks or palm oil gavage failed to stimulate VLDL(1) production in vivo. Reconstitution of apoC-III expression using adenovirus encoding human apoC-III resulted in robust production of VLDL(1) containing apoB-100 or apoB-48. The stimulatory effect of human apoC-III on the assembly and secretion of VLDL(1) was recapitulated ex vivo in McA-RH7777 cells cultured in lipid-rich media. Metabolic labeling experiments showed that apoC-III plays a central role in (i) the formation of lumenal lipid droplets (LLD) rich in TAG, and (ii) promoting bulk TAG incorporation during VLDL(1) assembly. Structure-function analysis of naturally occurring apoC-III variants (Ala23Thr and Lys58Glu) defined two functional domains that play respective roles in LLD formation and VLDL(1) assembly. Unraveling the intracellular role of apoC-III in the atherogenic TAG-rich VLDL(1) production provides new insights into the strong influence of the APOA5-A4-C3-A1 gene locus on plasma TAG concentrations and premature atherosclerosis.
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Ontario, Canada. zyao@uottawa.ca
authors.forename: Zemin
authors.initials: Z
authors.lastname: Yao
mesh_terms: D000818:Animals; D053305:Apolipoprotein C-III / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008079:Lipoproteins, VLDL / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*
chemical_list: D053305:Apolipoprotein C-III; D008079:Lipoproteins, VLDL