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Changes in high-density lipoprotein (HDL) subclass distribution were evaluated in a group of premature infants during the early postnatal period to ascertain whether enteral feeding brought about a rapid shift from neonatal to adult-like distributions. All infants were fed a combination of breast milk and formula. Cord blood of premature infants had a predominance of large, less dense (HDL2b)gge and a paucity of intermediate-sized (HDL3a)gge particles. Lack of a peak in the (HDL3a)gge is a characteristic feature for cord blood, whereas a prominent (HDL3a)gge peak is characteristic of adult plasma. After the start of enteral feeding, blood was obtained at two time-points: 6-14 days (sample A) and 17-32 days (sample B) postdelivery. With the onset of feeding, triglyceride increased significantly from an average of 34 mg/dl in cord blood to 120 mg/dl in sample B, and cholesterol increased from 86 to 112 mg/dl in the same period. Increases in plasma lipid concentrations were paralleled by a redistribution of subclasses such that three components of almost equal intensity were evident in sample B; these consisted of (HDL2b)gge, (HDL2a2)gge, and (HDL3b)gge. A paucity of (HDL3a)gge particles persisted even after onset of enteral feeding; thus, increases in plasma triglyceride and cholesterol per se are not sufficient to induce the adult-like distribution. It is suggested that development of the normal adult HDL subclass pattern is complex and is probably related to the development and interaction of several factors, including plasma enzymes involved in lipid hydrolysis and esterification, lipid exchange proteins, and hormonal status.

Hydrocortisone administration to infant rats enhanced cellobiase and maltase activities and induced precocious expression of sucrase and trehalase activities along the length of the small intestine. These activity changes reflected proportional concentration increases in the enzymes lactase (EC 3.2.1.23), maltase/glucoamylase (EC 3.2.1.20) and sucrase-isomaltase (EC 3.2.1.48/10). Administration of an equivalent tracer dose of [3H]leucine (by body weight) to control and hydrocortisone-treated infant rats resulted in greater accumulation of label in the carbohydrase pools of the treated rats, suggesting their increased de novo synthesis. The increased concentrations of lactase and maltase/glucoamylase induced by exogenous hydrocortisone were matched by the presence of corresponding greater amounts of label in their brush border pools. Accumulation of label in each of the lactase, maltase/glucoamylase and sucrase-isomaltase pools was generally similar in the hydrocortisone-treated rats, suggesting equivalent stimulation of their synthesis as a group by the humoral agent. The turnover rates of the carbohydrases as a group were found to be similar and did not appear to differ in control and hydrocortisone-treated rats. Total protein synthesis rates were slightly greater in the intestine of the hydrocortisone-treated group of rats.

Plasma lipid concentrations and high density lipoprotein (HDL) subclass distributions were evaluated in 22 newborn infants nourished with intravenous (iv)-fat. The majority of infants were premature with respiratory distress syndrome. Based on baseline (prior to iv-fat) HDL subclass profiles determined by gradient gel electrophoresis (GGE), infants fell into two classes, one with two or more pronounced peaks within the normal HDL spectrum (group I, 17 subjects) and the other with highly unusual HDL distribution (group II, five subjects). Total plasma cholesterol increased in both groups during low and high fat intravenous feeding. HDL-cholesterol, however, did not change with iv-fat where mean values for groups I and II at baseline, iv-low fat and -high fat were: group I, 31.2 +/- 7.1, 30.0 +/- 8.8, and 36.6 +/- 16.7 mg/dl, respectively; and group II, 20.0 +/- 7.8, 20.2 +/- 7.4, and 19.8 +/- 8.8 mg/dl, respectively. Unlike HDL-cholesterol levels that remained constant with iv-fat, apolipoprotein (apo) AI concentrations increased significantly: group I, 73.0 +/- 11.0, 88.3 +/- 15.9, and 93.1 +/- 21.9 mg/dl, respectively; and group II, 31.8 +/- 10.5, 41.0 +/- 12.8, and 59.3 +/- 18.5 mg/dl, respectively. In group I infants, iv-fat is associated with an increase in larger-sized particles, particularly in the (HDL2b)gge range; in group II there is an increase in (HDL3b)gge and (HDL3c)gge components and a disappearance of particles that fall outside of the size range of normal HDL. In both groups, enteral feeding is associated with a further normalization of HDL subclass distribution. The aberrant GGE profiles and very low apoAI levels of group II infants at baseline were associated with unusual HDL morphology determined by electron microscopy where discoidal structures were prominent. With iv-fat, discoidal particles decline in number while normal spherical structures increase. Prevalence of discoidal HDL at baseline was associated with low concentrations of lecithin:cholesterol acyltransferase (LCAT) (1.12 +/- 0.5 micrograms/ml); with iv-fat this enzyme rose to 1.61 +/- 0.18 micrograms/ml. Increased LCAT is associated with the normalization of HDL morphology. It is likely that iv-fat improves the nutritional status of premature infants, thereby stimulating increased liver synthesis of important proteins, including apoAI and LCAT, associated with HDL metabolism.

Cells of the intestinal mucosa of the infant and adult rat maintain a pattern of continuous growth, accumulating structural and functional proteins and lipids while migrating the length of the villus column. Cells of jejunal and ileal segments were fractionated sequentially from villus tip to inner crypt and distribution patterns were determined for DNA, total protein, cholesterol, phospholipid, and disaccharidases. Patterns of increasing ratios of protein, lipids, and disaccharidases to DNA were maintained to villus tips, with only slight fall-off of enzymes observed. Distribution profiles of disaccharidases, when computed relative to protein (as seen in previous reports), show distortion of the true cellular distribution pattern of these enzymes as determined by the DNA content of the fractions. Wide variation in cell protein concentrations was evident between jejunal and ileal segments in pre- and postweaned rats. Ileal cells of the suckling rat contained particularly high protein concentrations, which appeared to be largely transitory in nature and related to food intake. Cholesterol and phospholipids were found to be concentrated in the microvillus membrane and account for a significantly large fraction of the cellular content of these lipids.

We have examined the nature of the decline of lactase (EC 3.2.1.23) activity in the maturing rat intestine. It was established in an initial study that the activity decline reflected a proportional reduction in the concentration of the enzyme protein. Accumulation patterns of label into lactase, total intestinal proteins and sucrase (EC 3.2.1.48)-isomaltase (EC 3.2.1.10) were compared, 4 h following administration of a tracer dose of [3H]leucine to weanling rats exhibiting a wide range of lactase decline. Accumulation of increasing amounts of label in total intestinal proteins and sucrase-isomaltase pools was found to accompany the lactase decline, in contrast to accumulation of a constant amount of label in the declining lactase pools. The pattern of increased label accumulation in total intestinal proteins was shown in a corollary study to reflect a corresponding acceleration of total protein synthesis. On this basis, the finding of a constant amount of label in the declining lactase pools suggested a constant synthesis of lactase. We proposed earlier that associated reductions in enterocyte life-span (leading to correspondingly less lactase accumulation) rather than suppressed synthesis may provide the primary causal basis of lactase decline in the postweaned mammal.