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Journal of Lipid Research, Vol 28, 388-402, Copyright © 1987 by Lipid Research, Inc.
Intestinal apolipoprotein A-I and B-48 metabolism: effects of sustained alterations in dietary triglyceride and mucosal cholesterol flux
NO Davidson, AM Magun, TA Brasitus and RM Glickman
In recent studies (1985. J. Lipid Res. 26:368-379 and 1986. J. Lipid Res.
27:30-39) we characterized aspects of synthesis of rat intestinal
apolipoproteins (apo) A-I and B-48 in vivo, and their short term regulation
by dietary and biliary lipid flux. We now report studies extending these
observations to the effects on intestinal apoA-I and apoB-48 metabolism of
sustained (3 or 6 weeks) isocaloric intake of diets containing 0-30% (by
weight) triglyceride, the latter as either butter fat (saturated) or corn
oil (polyunsaturated). Additional studies were conducted to determine,
separately, the effects of perturbations of intestinal mucosal cholesterol
flux and hypothyroidism on intestinal apoA-I and apoB-48 metabolism.
Intestinal synthesis (% total protein) of apoA-I and apoB-48 was not
influenced by either dietary triglyceride quantity or quality (saturated
vs. polyunsaturated fat); the values that were obtained were strictly
comparable to those of both chow-fed animals and animals maintained for 3
weeks on fat-free chow. Intestinal apoA-I synthesis was not influenced by
either acute or chronic perturbations of mucosal cholesterol flux.
Hypothyroid rats demonstrated a 50% suppression of jejunal apoA-I
synthesis. Intestinal synthesis of apoB-48, by contrast, appeared to
undergo regulation by chronic (but not acute) perturbations of mucosal
cholesterol flux. Maneuvers that augmented intestinal cholesterol uptake
(particularly hypothyroidism) appeared to suppress intestinal apoB-48
synthesis by over 40%, while Surfomer (AOMA) administration reduced
cholesterol absorption (control, 54 +/- 7%; AOMA, 26 +/- 8%; P less than
0.0005) and resulted in a 24% increase in apoB-48 synthesis by jejunal
enterocytes. Intracellular intestinal lipoproteins demonstrated marked
cholesteryl ester enrichment of the triglyceriderich lipoprotein fractions
in hypercholesterolemic, hypothyroid rats. When all the groups were
compared, cholesterol absorption (used as an index of mucosal cholesterol
uptake) was negatively correlated with jejunal apoB- 48 synthesis (r =
-0.92, P less than 0.05). The data suggest that regulation of rat
intestinal apoA-I and apoB-48 metabolism is independent of triglyceride
flux. It is further concluded that an important regulatory effect of
mucosal cholesterol flux can be demonstrated on enterocyte apoB-48
synthesis. Finally, the data suggest the additional possibility that
circulating levels of thyroid hormone may exert an independent effect on
the expression of rat intestinal apolipoproteins A-I and B-48.

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Copyright © 1987 by the American Society for Biochemistry and Molecular Biology.
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