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.