Apolipoprotein A-V is present in bile and its secretion increases with lipid absorption in Sprague-Dawley rats.
Apolipoprotein (apo) A-V is a protein synthesized only in the liver that dramatically modulates plasma triglyceride levels. Recent studies suggest a novel role for hepatic apoA-V in regulating the absorption of dietary triglycerides, but its mode of action on the gut remains unknown. The aim of this study was to test for apoA-V in bile and to determine whether its secretion is regulated by dietary lipids. After an overnight recovery, adult male Sprague-Dawley bile fistula rats indeed secreted apoA-V into bile at a constant rate under fasting conditions. An intraduodenal bolus of intralipid (n = 12) increased the biliary secretion of apoA-V but not of other apolipoproteins, such as A-I, A-IV, B, and E. The lipid-induced increase of biliary apoA-V was abolished under conditions of poor lymphatic lipid transport, suggesting that the stimulation is regulated by the magnitude of lipids associated with chylomicrons transported into lymph. We also studied the secretion of apoA-V into bile immediately following bile duct cannulation. Biliary apoA-V increased over time (∼6-fold increase at hour 16, n = 8) but the secretions of other apolipoproteins remained constant. Replenishing luminal phosphatidylcholine and taurocholate (n = 9) only enhanced apoA-V secretion in bile, suggesting that the increase was not due to depletion of phospholipids or bile salts. This is the first study to demonstrate that apoA-V is secreted into bile, introducing a potential route of delivery of hepatic apoA-V to the gut lumen. Our study also reveals the uniqueness of apoA-V secretion into bile that is regulated by mechanisms different from other apolipoproteins.
Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio; zhangld@mail.uc.edu.
Linda S
LS
Zhang
Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio;
Hirokazu
H
Sato
Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio;
Qing
Q
Yang
Center for Prevention of Obesity, Cardiovascular Disease & Diabetes, Children's Hospital Oakland Research Institute, Oakland, California; and.
Robert O
RO
Ryan
Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, Missouri.
David Q-H
DQ
Wang
Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio;
Philip N
PN
Howles
Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio;
Patrick
P
Tso
D000818:Animals; D000072040:Apolipoprotein A-V; D001053:Apolipoproteins / Q000378:metabolism*; D001646:Bile / Q000378:metabolism*; D001658:Biliary Fistula / Q000378:metabolism*; D002914:Chylomicrons / Q000378:metabolism; D004195:Disease Models, Animal; D004386:Duodenum / Q000378:metabolism*; D004655:Emulsions / Q000008:administration & dosage / Q000378:metabolism; D005215:Fasting / Q000378:metabolism; D007408:Intestinal Absorption; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008196:Lymph / Q000378:metabolism; D008297:Male; D010713:Phosphatidylcholines / Q000494:pharmacology; D010743:Phospholipids / Q000008:administration & dosage / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D013024:Soybean Oil / Q000008:administration & dosage / Q000378:metabolism*; D013656:Taurocholic Acid / Q000494:pharmacology; D013997:Time Factors; D015854:Up-Regulation
C514818:Apoa5 protein, rat; D000072040:Apolipoprotein A-V; D001053:Apolipoproteins; D002914:Chylomicrons; D004655:Emulsions; D010713:Phosphatidylcholines; D010743:Phospholipids; C545823:soybean oil, phospholipid emulsion; D013656:Taurocholic Acid; D013024:Soybean Oil
bile fistula; bile salts; chylomicron; fat absorption; negative feedback regulation