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Biomedical subjects

M Hamosh

Publications and source records attributed to M Hamosh.

At least 37 records · Page 2Linked to original sources

Digestive lipases of the newborn ferret: compensatory role of milk bile salt-dependent lipase.

The amount of mRNA hybridizing to bile salt-dependent lipase and to colipase-dependent lipase probes as well as their translation into active proteins were quantified in the adult and newborn pancreas and lactating mammary gland from the ferret, a species whose milk, similar to that of the human, has bile salt-dependent lipase. The concentration of colipase-dependent lipase mRNA correlated with the amount of activity found in the adult and newborn pancreas, whereas neither mRNA nor activity of this enzyme was detected in the kit pancreas or in the lactating mammary gland. These data indicate that colipase-dependent lipase is actually expressed in adult pancreas and might represent the main lipolytic system in the adult. mRNA hybridizing to the bile salt-dependent lipase probe used in this study were detected in adult and in newborn ferret pancreas as well as in lactating mammary gland. However, the bile salt-dependent lipase activity expressed in the newborn pancreas was very low when compared with the activity expressed either in the mammary gland or in the adult pancreas. These data argue for a compensatory role of milk bile salt-dependent lipase in lipid digestion in the newborn. The hydrolysis of dietary fat might be initiated by preduodenal lipase, the activity of which is only two times lower in the gastric mucosa of the newborn than in the adult ferret. The high concentration of mRNA hybridizing to the bile salt-dependent lipase probe associated with a very poor bile salt-dependent lipase activity and protein suggests either that these mRNA are very unstable or that they are poorly translated into an active pancreatic bile salt-dependent lipase.

Animals↗

Effect of human milk or formula on gastric function and fat digestion in the premature infant.

The effect of diet, human milk or formula, on gastric function (lipase and pepsin activity, pH, and volume) and intragastric digestion of fat was assessed in 28 appropriate for gestational age preterm infants (gestational age, 28.9 +/- 1.4, 29.1 +/- 0.9, 29.5 +/- 0.6 wk; birth weight, 1.00 +/- 0.14 to 1.18 +/- 0.07 kg). The infants were fed either human milk (n = 11), SMA Super Preemie formula (n = 9), or Similac, Special Care formula (n = 8). Fasting and postprandial activity of digestive enzymes, pH, and gastric volume (measured before or during 50 min after gavage feeding) did not differ as a function of diet among the three groups of infants. Gastric lipase output, 23.1 +/- 5.1, 28.3 +/- 6.6, and 22.5 +/- 6.4 (U/kg of body weight) in human milk-, SMA SP-, or Similac SC-fed infants was comparable to the gastric lipase output of healthy adults fed a high fat diet (22.6 +/- 3.0). Pepsin output was, however, significantly lower (597 +/- 77, 743 +/- 97, and 639 +/- 142 U/kg of body weight) in human milk-, SMA SP-, and Similac SC-fed infants) than in healthy adults (3352 +/- 753 U/kg). The hydrolysis of dietary fat was 1.7-2.5-fold higher (p < 0.01) in human milk-fed infants than in infants fed either formula. We conclude that differences in type of feeding, i.e. different fatty acid profiles (long chain or medium chain triglycerides), different emulsions (natural or artificial), and different fat particle sizes do not affect the level of activity of gastric enzymes. However, the triglyceride within milk fat globules appears to be more accessible to gastric lipase than that within formula fat particles. We suggest that the contribution of gastric lipase to overall fat digestion might be greater in the newborn (a period of pancreatic insufficiency) than in the adult.

Dietary Fats↗

Breastfeeding and the working mother: effect of time and temperature of short-term storage on proteolysis, lipolysis, and bacterial growth in milk.

BACKGROUND: Women who breastfeed have to store expressed milk while at work for later feeding to their infants; however, storage conditions are often not optimal. OBJECTIVE: Top assess microbial growth and stability of milk protein and lipid at 15 degrees C to 38 degrees C for up to 24 hours. METHODS: Sixteen healthy women who breastfed exclusively, either at home (n=11) or who expressed milk for their infants (n=5), were studied during early (1 month) or late (5 to 6 months) lactation. Expressed milk was stored at 15 degrees C, 25 degrees C, and 38 degrees C for 1 to 24 hours for quantitation of pH, proteolysis, and lipolysis; bacterial growth was quantified at 0, 4, 8, and 24 hours of storage. RESULTS: Milk pH decreased 2 units by 24 hours of storage at all temperatures tested. Proteolysis was minimal during milk storage at 15 degrees C or at 25 degrees C for 24 hours and was apparent only after 24 hours of storage at 38 degrees C. Lipolysis was rapid, starting in the first hours of storage and progressing to 8% at 24 hours. Thus, while the greatest increment in proteolysis products was a 40% increase above baseline after 24 hours of storage at 38 degrees C, free fatty acid concentration at this storage time was 440% to 710% higher than in freshly expressed milk. Bacterial growth was restricted mainly to nonpathogens, was minimal at 15 degrees C throughout the 24 hours of storage, was low at 25 degrees C for the first 4 to 8 hours, and was considerably higher at 38 degrees C even during the relatively short period of 4 hours. CONCLUSIONS: Storage of human milk is safe at 15 degrees C for 24 hours, whereas at 25 degrees C it is safe for 4 hours. Milk should not be stored at 38 degrees C. Minimal proteolysis during storage suggests that milk proteins probably maintain their structure and function during short-term storage, while the marked lipolysis might slow bacterial growth during this time.

Adult↗

Digestion in the newborn.

Although the various aspects of digestion in the newborn have been studied for decades, we still lack quantitative information about the contribution of individual enzymes to the overall process. The information to date indicates that in spite of immaturity of many of the classical digestive mechanisms of the adult, the infant uses a number of compensatory systems to achieve adequate digestion of nutrients (Fig. 1). Thus, whereas in the infant gastric proteolysis is probably extremely limited, intestinal protein digestion is adequate. Although starch supplements are better tolerated in breast-fed infants, because of the compensation provided by human milk amylase, the infant is able to digest lactose and short-chain glucose polymers with endogenous brush border enzymes. Fat digestion is markedly aided by gastric lipase and, in breast-fed infants, the bile salt-dependent lipase of human milk. Thus, in the infant, gastric lipolysis is quantitatively much more significant than in adults. The absorption of human milk whey proteins (and probably also cow milk proteins) is probably associated more with the highly glycosylated form of these proteins than with immaturity of neonatal digestive enzymes.

Adult↗

Breastfeeding: Unraveling the Mysteries of Mother's Milk.

Most of the major progress in understanding the unique and complex features of human breast milk has emerged in just the past 2 decades. Since the late 1970s, key research has examined such aspects as the composition of breast milk, effects of maternal and environmental factors on human milk, and the effect of human milk on the infant, including the protection against disease that breast milk can confer on the newborn. The composition of human breast milk includes growth factors, hormones, enzymes, and other substances that are immune-protective and foster proper growth and nutrition in the newborn. Research suggests that lactation is robust and that a mother's breast milk is adequate in essential nutrients, even when her own nutrition is inadequate. Mature breast milk usually has constant levels of about 7g/dL carbohydrate and about 0.9g/dL proteins. But the composition of fats essential for neonatal growth, brain development, and retinal function varies according to a woman's intake, the length of gestation, and the period of lactation. Vitamins and minerals also vary according to maternal intake. But even when these nutrients are lower in breast milk than in formulas, their higher bioactivity and bioavailability more nearly meet the complete needs of neonates than do even the best infant formulas. Also, in many instances human milk components compensate for immature function, such as a neonate's inability to produce certain digestive enzymes, immunoglobulin A (IgA), taurine, nucleotides, and long-chain polyunsaturated fatty acids.

Journal Article↗

Lipoprotein lipase activity and its relationship to high milk fat transfer during lactation in grey seals.

Lipoprotein lipase regulates the hydrolysis of circulating triglyceride and the uptake of fatty acids by most tissues, including the mammary gland and adipose tissue. Thus, lipoprotein lipase is critical for the uptake and secretion of the long-chain fatty acids in milk and for the assimilation of a high-fat milk diet by suckling young. In the lactating female, lipoprotein lipase appears to be regulated such that levels in adipose tissue are almost completely depressed while those in the mammary gland are high. Thus, circulating fatty acids are directed to the mammary gland for milk fat production. Phocid seals serve as excellent models in the study of lipoprotein lipase and fat transfer during lactation because mothers may fast completely while secreting large quantities of high fat milks and pups deposit large amounts of fat as blubber. We measured pup body composition and milk fat intake by isotope (deuterium oxide) dilution and plasma post-heparin lipoprotein lipase activity in six grey seal (Halichoerus grypus) mother-pup pairs at birth and again late in the 16-day lactation period. Maternal post-heparin lipoprotein lipase activity increased by an average of four-fold by late lactation (P = 0.027), which paralleled an increase in milk fat concentration (from 38 to 56%; P = 0.043). Increasing lipoprotein lipase activity was correlated with increasing milk fat output (1.3-2.1 kg fat per day) over lactation (P = 0.019). Maternal plasma triglyceride (during fasting) was inversely correlated to lipoprotein lipase activity (P = 0.027) and may be associated with the direct incorporation of long-chain fatty acids from blubber into milk. In pups, post-heparin lipoprotein lipase activity was already high at birth and increased as total body fat content (P = 0.028) and the ratio of body fat: protein increased (P = 0.036) during lactation. Although pup plasma triglyceride increased with increasing daily milk fat intake (P = 0.023), pups effectively cleared lipid from the circulation and deposited 70% of milk fat consumed throughout lactation. Lipoprotein lipase may play an important role in the mechanisms involved with the extraordinary rates of fat transfer in phocid seals.

Animals↗

Lipid metabolism in pediatric nutrition.

The abrupt transition from carbohydrate to fat as the main energy source that occurs at birth is not matched by commensurate endogenous fat-digesting capacity in the newborn. Newborn infants are, however, able to digest fat efficiently through the activities of gastric lipase and the exogenous digestive lipase of human milk, which compensate for the low activity of pancreatic lipase. Fat absorption is well-developed at birth and is commensurate with the high fat intake of the infant. Tissue uptake of dietary fat is also adequate, based on sufficient lipoprotein lipase (above 26 to 27 weeks' gestation) and rapid postnatal increase of lecithin:cholesterol acyl transferase, the enzymes that regulate tissue uptake of circulatory lipoprotein triglyceride and cholesterol.

Child↗

Dietary fat modulates gastric lipase activity in healthy humans.

The aim of this study was to determine whether the amount of dietary fat modulates the activity of gastric lipase in humans. Gastric juice was collected from six healthy subjects after 2-wk periods of either a high-fat (50% of energy as fat) or low-fat (25% of energy as fat) diet. The collection period lasted 2 h, the first hour under baseline conditions and the second hour after pentagastrin stimulation (6 micrograms/kg body wt). Gastric lipase and pepsin activities were quantitated at 15-min intervals and total enzyme outputs were calculated. Under baseline conditions there was a tendency for higher output of gastric lipase and pepsin after the high-fat diet than after the low-fat diet (gastric lipase: 745 compared with 446 U/h, pepsin: 107,677 compared with 78,505 U/h). The difference in output between diet groups was significant after pentagastrin stimulation (gastric lipase: 1323 compared with 875 U/h, pepsin: 191,751 compared with 128,961 U/h, for high-fat compared with low-fat diet, respectively, P < 0.05). This study is the first to report that a high-fat diet leads to an increase in the activity of gastric enzymes in humans.

Adaptation, Physiological↗

Plasma lecithin: cholesterol acyltransferase and plasma lipolytic activity in preterm infants given total parenteral nutrition with 10% or 20% Intralipid.

The effect of 10% or 20% Intralipid on lipid clearing enzymes, plasma lipids and apoproteins was investigated during the first 5 days after birth in 37 premature infants maintained on total parenteral nutrition; 21 infants received 20% and 16 received 10% Intralipid, respectively. Lipid was infused over a 20-h period at rates of 1, 2 and 3 g/kg/day on consecutive days. Plasma lecithin: cholesterol acyltransferase (LCAT) activity was low and increased significantly (p<0.05) only during infusions of 3 g/kg/day in both groups of infants. Plasma lipolytic activity was generally not affected by the regimen or preparation (10% or 20%) of Intralipid infused, except for higher (p<0.05) levels at 3 g/kg/day of 20% compared with prelipid infusion. Plasma triglyceride concentrations wer similar after 10% or 20% Intralipid, whereas plasma total cholesterol was significantly higher during infusion of 2 and 3 g/kg/day of 10% compared with 20% Intralipid. The efficient clearing of 20% Intralipid might be related to the lower lecithin: triglyceride ration which is compatible with the low LCAT activity of premature infants.

Apolipoproteins A↗

Fatty acid and positional selectivities of gastric lipase from premature human infants: in vitro studies.

Gastric lipase activity in aspirates from premature human infants was tested for fatty acid and positional selectivity using racemic diacid triacylglycerols (TG) as substrates. The resulting free fatty acids and monoacylglycerols (MG) were recovered and analyzed. Octanoic acid (8:0) and decanoic acid (10:0) were hydrolyzed with a preference of 61.5:1 and 2.4:1 compared to palmitic acid (16:0) from rac-16:0-8:0-8:0 and rac-16:0-10:0-10:0, respectively. The ratio of lauric acid (12:0) to oleic acid (18:1) hydrolyzed from rac-18:1-12:0-12:0 was 13:1. Myristic acid (14:0), 18:1 and linoleic acid (18:2) were released at similar rates. These data and the composition of the MG suggest that, in vitro, the lipase is selective for shorter chain fatty acids and for fatty acids on the primary positions of the TG backbone.

Caprylates↗

Use of high-fat formula for premature infants with bronchopulmonary dysplasia: metabolic, pulmonary, and nutritional studies.

The use of dietary fat in preference to carbohydrate offers the theoretic advantage of diminishing carbon dioxide production and thus the respiratory quotient, which may be beneficial for babies with chronic lung disease. Ten premature infants (birth weight (mean +/- SEM), 1.13 +/- 0.12 kg; postnatal age, 9 +/- 1 weeks) with bronchopulmonary dysplasia were alternately fed a high-fat and a high-carbohydrate formula each for 1 week, in randomized order. Lower rates of carbon dioxide production (6.6 +/- 0.3 versus 7.4 +/- 0.4 ml/kg per minute; p < 0.05), and consequently lower respiratory quotients (0.80 +/- 0.02 versus 0.94 +/- 0.01 ml/kg per minute; p < 0.005), were observed during the administration of the high-fat formula. There were no significant differences in results of pulmonary function tests with the use of either formula. Both formulas were equally well tolerated and able to promote adequate growth and normal biochemical profiles. However, weight gain was significantly greater with the administration of the high-carbohydrate formula, possibly because of an increase in the accretion of body fat. We conclude that the short-term use of high-fat formula for infants with bronchopulmonary dysplasia decreases carbon dioxide production while maintaining adequate growth and nutritional status.

Bottle Feeding↗

Milk fat yield and composition during abomasal infusion of cis or trans octadecenoates in Holstein cows.

The role of trans-C18:1 fatty acids in milk fat depression was examined. Six rumen-cannulated Holstein cows were assigned to two Latin squares with 21-d periods. The common basal diet contained 40% forage and 60% concentrate. Treatments were the uninfused control, 750 g/d of a mixture of cis fat (65% high oleic sunflower oil and 35% cocoa butter), and 750 g/d of a mixture of trans fat (93% shortening and 7% corn oil) infused into the abomasum via a tube that passed through the rumen cannula. Milk yield was similar among treatments. Milk fat percentage and yield were lower, and milk citrate concentration was higher, for the trans than the cis treatment. Changes in the fatty acid composition of milk were similar for the cis and trans treatments compared with the control except for trans-C18:1. The concentration of trans-C18:1 was greater for the cis and trans treatments than for the control and was greater for the trans than for the cis treatment. These data clearly demonstrated that infusion of trans-C18:1 fatty acids into the abomasum depressed milk fat percentage and yield. We speculate that reduced synthesis of fatty acids and reduced activity of acyl transferase in mammary tissue contributed to depressed milk fat percentage for the trans treatment.

Abomasum↗

Human milk in disease: lipid composition.

Differences in the lipid composition of human milk have been described in maternal diseases known to affect fat metabolism. Diseases such as diabetes, cystic fibrosis, hypobetalipoproteinemia and Type I hyperlipoproteinemia affect the quantity and quality of human milk fat. Increased fatty acid chain elongation and changes in desaturation (especially delta 6 desaturase), as well as changes in lipid class composition, have been shown in diabetes and cystic fibrosis, whereas compensatory increases in medium-chain fatty acids have been described in hypobetalipoproteinemia and Type I hyperlipoproteinemia. It is important to realize that these observations were made either on single women or on very small groups of women. In infant diseases, such as breast milk jaundice and ectopic eczema, changes in polyunsaturated fatty acids in maternal milk have been described.

Cystic Fibrosis↗

Human mammary gland function at the onset of lactation: medium-chain fatty acid synthesis.

The onset of medium-chain fatty acid synthesis in the human mammary gland was investigated. Colostrum and serum were collected from 31 healthy women and the fatty acid composition of total lipid was analyzed by gas-liquid chromatography. Although colostrum/serum ratios for most fatty acids range from 0.7-2.4, very low levels of 10:0 and 12:0 were present in serum lipids as compared to much higher concentrations of these fatty acids in colostrum lipids (colostrum/serum ratio 16.23 and 17.11 for 10:0 and 12:0, respectively). We have previously found that medium-chain fatty acid levels are very low in prepartum mammary secretions (6-10 wk before term delivery) but are higher and similar in colostrum of women who deliver preterm (3-14 wk) or at full term. The data indicate that parturition, irrespective of length of pregnancy, is the trigger for medium-chain fatty acid synthesis in the human mammary gland.

Breast↗