Journal
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
Volume 294, Issue 1, Pages G344-G352Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpgi.00123.2007
Keywords
very low-density lipoprotein; lymph
Categories
Funding
- NHLBI NIH HHS [HL-38180] Funding Source: Medline
- NIDDK NIH HHS [DK-52574, DK-56863, DK-59630, DK-38180, P30 DK056341, P30 DK056341-07, DK-56910, DK-76928, P30 DK056341-08, DK-56260] Funding Source: Medline
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R37HL038180, R01HL038180] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P01DK056863, P30DK052574, U2CDK059630, P30DK056341, R01DK056260, R01DK056910, U24DK059630, R01DK076928] Funding Source: NIH RePORTER
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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 mu mol/h of triolein). KO mice transported triacylglycerol (TG) as efficiently as WT mice when infused with the lower lipid dose; when infused with 6 mu mol/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.
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