Journal of Lipid Research, Vol 22, 1111-1118, Copyright © 1981 by Lipid Research, Inc.
In vivo regulation of canine intestinal 3-hydroxy-3-methylglutaryl coenzyme A reductase by cholesterol, lipoprotein, and fatty acids
RL Gebhard and WF Prigge
Thirty-Vella-isolated ileal segments in dogs were used to study the
regulation of intestinal cholesterol synthesis. This excluded fistula
enabled independent in vivo manipulation of luminal and vascular influences
on mucosal cells. Segments were studied repeatedly and each animal served
as its own control. Cholesterol synthesis rate was assessed by measuring
mucosal activity of the rate-limiting enzyme 3- hydroxy-3-methylglutaryl
coenzyme A (HMG CoA) reductase. Luminal cholesterol and
25-hydroxycholesterol were shown to reduce HMG CoA reductase activity to 64
+/- 7% and 42 +/- 4%, respectively, of control within 4 hr. Reductase
activity in the excluded segment also responded to alterations in serum
cholesterol produced by cholesterol or cholestyramine feeding. Similarly,
in vitro studies showed that lipoprotein cholesterol inhibited HMG CoA
reductase in mucosa from the excluded segment but not in mucosa from intact
bowel. In contrast to sterols, fatty acids stimulated HMG CoA reductase
activity by luminal contact. These findings suggest that the cholesterol
needs of canine intestinal epithelial cells are acutely balanced by
absorption and synthesis of cholesterol. Mucosal cells may also utilize
lipoprotein cholesterol under certain conditions, perhaps via low density
lipoprotein receptors. Fatty acid absorption stimulated cholesterol
synthesis in the absence of luminal cholesterol, perhaps to facilitate
chylomicron formation.
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