title: Evolution and mechanism of apolipoprotein B-containing lipoprotein assembly.
abstract: OBJECTIVE
  Apolipoprotein B-containing lipoprotein assembly and secretion is critical for lipid absorption and triglyceride homeostasis, and plays a role in atherogenesis and the pathobiology of type 2 diabetes and obesity. This review highlights recent insights into the evolutionary, structural, and cell biology of hepatic and intestinal pathways for lipid mobilization, and the mechanisms and regulation of lipoprotein assembly and secretion.
  
  
  RESULTS
  Until recently it was assumed that microsomal triglyceride transfer protein-dependent apolipoprotein B-containing lipoprotein assembly was a unique adaptation associated with vertebrate lipid homeostasis. However, it is now clear that microsomal triglyceride transfer protein (MTP) exists in species whose last common ancestor diverged over 550 million years ago. In its long evolutionary history, the MTP gene has given rise to a series of paralogous lipid transport proteins, all of which require MTP for their biogenesis. During its evolution, MTP has acquired new functions, enabling it to participate in a disparate array of lipid mobilization and transport pathways, ranging from primitive lipoprotein assembly to antigenic lipid presentation. In addition to the complex and multifunctional role of MTP in apolipoprotein B assembly, other factors responsible for the generation of secretion-coupled lipids and the modulation of apolipoprotein B production are emerging.
  
  
  CONCLUSIONS
  The phylogenic dissection of MTP and apolipoprotein B function, coupled with ongoing structural and biochemical analyses, provide significant insights into the mechanisms of lipid mobilization and secretion. Some of these factors and processes may be targeted therapeutically to modulate the quantitative and qualitative aspects of apolipoprotein B production.
authors.affiliation: Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1040, USA.
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Shelness
authors.forename: Aubrey S
authors.initials: AS
authors.lastname: Ledford
mesh_terms: D001055:Apolipoproteins B / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000502:physiology*; D019143:Evolution, Molecular; D006706:Homeostasis; D006801:Humans; D050356:Lipid Metabolism; D008861:Microsomes; D014280:Triglycerides / Q000378:metabolism
chemical_list: D001055:Apolipoproteins B; D002352:Carrier Proteins; D014280:Triglycerides; C106092:microsomal triglyceride transfer protein