Why does the gut choose apolipoprotein B48 but not B100 for chylomicron formation?
Chylomicrons produced by the human gut contain apolipoprotein (apo) B48, whereas very-low-density lipoproteins made by the liver contain apo B100. To study how these molecules function during lipid absorption, we examined the process as it occurs in apobec-1 knockout mice (able to produce only apo B100; KO) and in wild-type mice (of which the normally functioning intestine makes apo B48, WT). Using the lymph fistula model, we studied the process of lipid absorption when animals were intraduodenally infused with a lipid emulsion (4 or 6 micromol/h of triolein). KO mice transported triacylglycerol (TG) as efficiently as WT mice when infused with the lower lipid dose; when infused with 6 micromol/h of triolein, however, KO mice transported significantly less TG to lymph than WT mice, leading to the accumulation of mucosal TG. Interestingly, the size of lipoprotein particles from both KO and WT mice were enlarged to chylomicron-size particles during absorption of the higher dose. These increased-size particles produced by KO mice were not associated with increased apo AIV secretion. However, we found that the gut of the KO mice secreted fewer apo B molecules to lymph (compared with WT), during both fasting and lipid infusion, leading us to conclude that the KO gut produced fewer numbers of TG-rich lipoproteins (including chylomicron) than the wild-type animals. The reduced apo B secretion in KO mice was not related to reduced microsomal triglyceride transfer protein lipid transfer activity. We propose that apo B48 is the preferred protein for the gut to coat chylomicrons to ensure efficient chylomicron formation and lipid absorption.
Lo
Chun-Min
CM
Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH 45237, USA.
Nordskog
Brian K
BK
Nauli
Andromeda M
AM
Zheng
Shuqin
S
Vonlehmden
Sarah B
SB
Yang
Qing
Q
Lee
Dana
D
Swift
Larry L
LL
Davidson
Nicholas O
NO
Tso
Patrick
P
D000071479:APOBEC-1 Deaminase; D000818:Animals; D053299:Apolipoprotein B-100 / Q000378:metabolism*; D053283:Apolipoprotein B-48 / Q000378:metabolism*; D001054:Apolipoproteins A / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002914:Chylomicrons / Q000378:metabolism*; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000201:enzymology / Q000378:metabolism*; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D007441:Intubation, Gastrointestinal; D008196:Lymph / Q000378:metabolism*; D008208:Lymphatic System / Q000601:surgery; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D010316:Particle Size; D013997:Time Factors; D014304:Triolein / Q000008:administration & dosage / Q000378:metabolism*
D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001054:Apolipoproteins A; D002352:Carrier Proteins; D002914:Chylomicrons; C022205:apolipoprotein A-IV; C106092:microsomal triglyceride transfer protein; D014304:Triolein; D000071479:APOBEC-1 Deaminase; C000605089:APOBEC1 protein, human; C000605090:Apobec1 protein, mouse; D003564:Cytidine Deaminase