Alterations in Piglet Small Intestine after Cholesterol Deprivation

Abstract

ABSTRACT. Mammalian cells require cholesterol for normal cell function. This requirement can be fulfilled by endogenous biosynthesis or by extracellular supplementation. Infants fed with human milk receive greater quantities of cholesterol than those fed commercial formulas. Whether this lack of cholesterol in commercial formulas poses a threat to normal neonatal cell function is not known. We compared small intestinal microvillus membrane fluidity, hydrolase activities, protein concentration, permeability to nonabsorbable markers, and weight gain in neonatal piglets receiving restricted intake of isocaloric formulas containing either normal amounts of cholesterol (145 mg/dl) or very low levels of cholesterol (<2 mg/dl). Using the fluorescent probe, diphenylhexatriene, and fluorescence polarization, microvillus membranes from cholesterol deprived piglets demonstrated higher fluidities than did microvillus membranes from animals fed normal concentrations of cholesterol. Cholesterol-deprived animals, even though their caloric intake was similar to cholesterol-fed animals, demonstrated a net weight loss per animal whereas the cholesterol-fed animals demonstrated a weight gain. These results demonstrate that in a pig model on a restricted intake, cholesterol deprivation alters the biophysical properties of the microvillus membrane. Little is known about the effect of dietary cholesterol on the developing small intestine. Human infants who are breast-fed have a higher cholesterol intake compared to formula-fed infants. Certain other mammalian species have even higher cholesterol concentrations in their milk, prompting inferences that cholesterol may be an important functional component of the diet. Some concepts that may mitigate the possible functional role of cholesterol in milk are: first, the membrane-stabilizing effect of cholesterol is a phenomenon described for many membrane systems (1-3) and motional freedom (fluidity) of lipids in the MVM (4) of the small intestine. The alterations in cholesterol content are associated with changes in the transport properties of glucose and bile acids in the ileum (5). In the rat, as the transport of active bile acids in the ileum develops during maturation, MVM fluidity decreases inversely with the increase in cholesterol-to-phospholipid ratio (5). These factors suggest a relationship between concentration of membrane cholesterol and function. Even though deprivation of dietary cholesterol may elevate endogenous biosynthesis of cholesterol (6), no evidence is available to demonstrate that the neonatal small intestine can adapt to cholesterol deprivation by accelerating cholesterol biosynthesis. Whether dietary cholesterol deprivation produces a threat to normal small intestinal function is unknown. The purpose of this investigation was to determine the effects of cholesterol deprivation on the small intestinal MVM of the neonatal pig on a restricted formula intake. METHODSAnimals. Neonatal pigs were farrowed at the University of Florida Swine Center. On day 1 10 of gestatio...

Apolipoprotein E knockout mice have accentuated malnutrition with mucosal disruption and blunted insulin-like growth factor I responses to refeeding

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Carboxyl ester lipase activity in milk prevents fat-derived intestinal injury in neonatal mice

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