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M Hamosh

Publications and source records attributed to M Hamosh.

At least 73 records · Page 4Linked to original sources

Gastric lipase: localization in the human stomach.

The aim of this study was to determine the range of activity and the location of lipase in the human stomach. The range of lipase activity in gastric mucosa of surgical specimens from the fundic area of 22 subjects was 594 to 3350 mU [mean, 1598 +/- 144 mU tri[3H]olein, (1 mU-1 nmol [3H]oleic acid released from tri[3H]olein per minute per milligram protein)]. For localization of activity, pinch biopsy specimens of gastric mucosa from 6 subjects were taken from the greater and lesser curvatures within 2 cm of the gastroesophageal junction (upper greater curvature and upper lesser curvature) and within 2 cm of the pylorus (lower greater curvature and lower lesser curvature). Lipase activity was higher in the upper greater curvature (405 +/- 92 mU) than in the upper lesser curvature (32 +/- 13 mU) and lowest in the antral area (16 +/- 9 mU in the lower lesser curvature and 10 +/- 2 mU in the lower greater curvature). The data show that in the human, lipase activity is localized primarily in the fundic area of the stomach. Comparison of the lipase activity levels in the gastric mucosa with lingual lipase activity levels in specimens of lingual serous glands indicates that in humans, gastric lipase is the main lipase active in the stomach.

Adult↗

Effect of heparin dose and infusion rate on lipid clearance and bilirubin binding in premature infants receiving intravenous fat emulsions.

The effect of heparin dose and infusion rate on plasma lipids, lipases, and unbound bilirubin was investigated in 22 premature infants with physiologic jaundice. Infants were randomly assigned to receive low or high intravenous doses (24 vs 137.3 U/day) of heparin. Each patient then received 2 g/kg/day of 10% Intralipid on 2 successive days: one day during a 15-hour period and the other day over 24 hours, with the order assigned randomly. The results demonstrate a significantly greater change in serum-free fatty acids in infants receiving the high heparin dose during the 15-hour lipid infusion period. Lipoprotein lipase activity rose more with the high heparin dose and equally at either infusion rate. We conclude that lipid infusions of 2 g/kg/day with low heparin dosage infused over 24 hours resulted in less elevation in serum-free fatty acids. There were no adverse effects on unbound bilirubin at either infusion rate or heparin dosage.

Bilirubin↗

Effect of total parenteral nutrition on lipase activity in the stomach of very low birth weight infants.

Lipase activity was quantitated in gastric aspirates of 7 premature infants (gestational age 24-29 weeks) during periods of total parenteral nutrition (TPN), mixed parenteral nutrition and gavage feeding or exclusive gavage feeding. The infants were studied from birth until the establishment of exclusive gastric gavage feeding. Lipase activity in gastric aspirates (quantitated by the hydrolysis of 3H-triolein at pH 4.2 and expressed in nmol 3H-oleic acid released/min/ml gastric aspirate) did not differ significantly as a function of mode of feeding: 570 +/- 235 during TPN, 260 +/- 145 during mixed parenteral nutrition and gavage feeding, and 374 +/- 149 during exclusive gastric gavage feeding. The data suggest that, contrary to the intestine and pancreas, the digestive function of the stomach is not impaired during TPN in the very preterm infant.

Humans↗

Low levels of apolipoprotein A1 are not contributors to the low lecithin-cholesterol acyl transferase activity in premature newborn infants.

Umbilical cord sera were obtained from three groups of newborn infants; group I (n = 8) and group II (n = 12) weighed less than 1500 g and between 1500 and 2500 g, respectively. Group III (n = 16) was full term and weighed more than 2500 g. Lecithin-cholesterol acyl transferase activities, determined as the rates of esterification of [3H]cholesterol, were 0.13 +/- 0.01, 0.17 +/- 0.01, and 0.26 +/- 0.01 (mean +/- SEM) nmol/h/ml for groups I, II, and III, respectively. The adult value (n = 8) was 0.96 +/- 0.01 nmol/h/ml. The respective apolipoprotein A1 (apo-A1) levels were 52 +/- 6, 59 +/- 4, and 67 +/- 4 (mean +/- SEM) mg/dl. Serum level of apo-A1 in adults was 137 +/- 6 mg/dl. Plasma high-density lipoprotein cholesterol levels increased with gestational age. However, in newborn infants, high-density lipoprotein apo-lipoprotein B, total cholesterol, and triglyceride levels, were significantly lower than in adults. These data indicate that serum levels of lecithin-cholesterol acyl transferase activity significantly (p less than 0.01) increase whereas the levels of apo-A1 do not significantly change with the gestational age. Also, in full-term newborns, lecithin-cholesterol acyl transferase activity is only 27%, whereas apo-A1 levels are 49% of adult values. Therefore, lower levels of apo-A1 do not account for the significantly lower activity of lecithin-cholesterol acyl transferase in preterm as compared to full-term newborn infants.

Apolipoproteins A↗

Role of nonpancreatic lipolytic activity in exocrine pancreatic insufficiency.

Patients with exocrine pancreatic insufficiency may absorb greater than 50% of dietary fat despite the absence of measurable pancreatic lipase activity. Nonpancreatic lipolytic activity was measured in gastric and duodenal aspirates from 5 patients with exocrine pancreatic insufficiency secondary to alcoholism and in aspirates from 5 alcoholics without evidence of exocrine pancreatic dysfunction (controls). Samples were collected under fasting and postprandial conditions. All patients with exocrine pancreatic insufficiency had nonpancreatic lipolytic activity in gastric and duodenal aspirates. Lipolytic activity in gastric aspirates was not significantly different between the patients with exocrine pancreatic insufficiency and the controls during the fasting and postprandial periods. Pancreatic insufficiency was associated with significantly (p less than 0.05) higher nonpancreatic lipolytic activity in the duodenum under fasting conditions. No significant difference between the groups was found in postprandial nonpancreatic lipolytic activity. Nonpancreatic lipolytic activity accounted for approximately 90% of total lipolytic activity at the ligament of Treitz in patients with exocrine pancreatic insufficiency as opposed to 7% in the control subjects. These observations suggest a significant role for nonpancreatic lipolytic activity (lingual lipase and gastric lipase) in fat digestion in patients with pancreatic insufficiency secondary to chronic alcohol abuse.

Alcoholism↗

Lipid metabolism in premature infants.

Fats provide 40-50% of the total calories in human milk or infant formula. The milk secreted by mothers of preterm infants differs in fat composition from that of mothers of full-term infants in having higher levels of medium chain fatty acids (C12, C14) throughout the first 3 months of lactation, and higher levels of long chain polyenoic fatty acids during the first 3 months of lactation. These differences in composition benefit the preterm infant by providing higher levels of rapidly absorbed medium chain fatty acids and long chain polyenoic fatty acids needed for brain development. Fat digestion: The low levels of pancreatic lipase and bile salts in the preterm infant are compensated for by lipolysis in the stomach by lingual and gastric lipase and by the intestinal hydrolysis of fat through the action of human milk bile salt-stimulated lipase. Fat digestion is efficient in the preterm infant who absorbs about 80-90% of ingested fat. Lipid clearing from the circulation depends upon the activity of the enzymes lipoprotein lipase, hepatic lipase, and lecithin-cholesterol acyltransferase. The activity of these enzymes is lower or equal to that of term infants, depending upon the degree of prematurity and the nutritional regimen, especially in parenterally fed infants.

Fatty Acids↗

Lipid composition of milk from mothers with cystic fibrosis.

Milk lipids from six mothers with cystic fibrosis were compared with milk lipids from six mothers without cystic fibrosis. Mean neutral lipids (in g/dL) were colostrum, 2.4; transitional, 2.9; mature milk, 2.9, suggesting that milk fat content was sufficient to support energy needs of the infant. Lipid class composition was normal, 98% being present as triglyceride. Cholesterol and cholesteryl ester concentrations were similar in the milk of both groups of lactating women. Phospholipid class distribution of cystic fibrosis milk was different from that in control milk. Approximately 85% of the lipids were present in six major fatty acids from 12:0 to 18:2 in both groups, indicating that the profile of most of the lipid was similar. The linoleic acid content of cystic fibrosis milk was decreased significantly to 75% of normal values. Other polyunsaturated fatty acids were elevated in cystic fibrosis milk. Concentrations of 16:2, 18:3, and several longer chain polyunsaturated fatty acids were twice that in the milk of the control women, suggesting increased delta 6-desaturation. Elevated proportions of several other polyunsaturated fatty acid metabolites suggested increased chain elongation to C20 and C22 polyunsaturated fatty acids. These differences in fatty acid patterns in cystic fibrosis milk were similar to differences found in blood lipid patterns of children with cystic fibrosis. These results suggest abnormal polyunsaturated fatty acid nutrition or metabolism in cystic fibrosis.

Cholesterol↗

Bile salt-stimulated lipase in non-primate milk: longitudinal variation and lipase characteristics in cat and dog milk.

We report the presence of bile salt-stimulated lipase in milk collected from dog and cat. This enzyme has previously been found only in the milk of human and gorilla. Bile salt-stimulated lipase activity in individual dog milk specimens (range: 4.8-107.4 U/ml; 1 U = 1 mumol [3H]oleic acid released/min) was similar, while that in cat milk specimens (range: 2.2-16.9 U/ml) was lower than in human milk (range: 10-80 U/ml). Longitudinal patterns for bile salt-stimulated lipase activity differed depending upon the enzyme source: in dog milk, lipase activity was lowest in colostrum, while in cat milk, lipase activity was highest in colostrum and decreased at mid-lactation. In human milk, bile salt-stimulated lipase activity levels remain fairly constant throughout the first 3 months of lactation. Dog, cat and human milk bile salt-stimulated lipase activity had a neutral-to-alkaline pH optimum of 7.3-8.5, was stable at low pH (above 3.0 for at least 1 h), and was inhibited 95-100% by eserine (at concentrations greater than 0.6 mM). The lipase in the milk of the three species studied had an absolute requirement for primary bile salts (tauro- and glycocholate), and was inhibited by secondary bile salts (tauro- and glycodeoxycholate). These data are the first to report bile salt-stimulated lipase activity in milk from mammals other than the highest primates. Presence of this lipase in non-primate milk will permit the study of the factors that regulate the ontogeny, synthesis and secretion of the enzyme during pregnancy and lactation as well as its function in neonatal fat digestion.

Animals↗

Lingual lipase.

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Animals↗

Intravenous administration of lipid emulsions to premature infants.

This article describes the mechanisms responsible for hydrolysis and clearance of triglyceride from the circulation and focuses on the factors that affect lipid clearance in the newborn infant. The potential beneficial and adverse effects of IV lipid administration to premature infants are reviewed in detail. Several practical considerations for IV lipid administration are also discussed.

Bilirubin↗

Secretion of human gastric lipase from dispersed gastric glands.

The presence of a triacylglycerol lipase in human gastric juice was described in previous studies. Its source and role in intragastric lipolysis was, however, uncertain. Our study presents definitive evidence for gastric origin of a lipase and its release by secretagogues. Both carbachol and cholecystokinin-8 stimulate release of this enzyme for dispersed human gastric glands. While the two secretagogues had similar efficacies, with nearly a 3-fold stimulation over basal rates, cholecystokinin-8 was about four orders of magnitude more potent in releasing lipolytic activity than carbachol (maximum stimulation at concentrations of 1 X 10(-9) and 1 X 10(-5) M, respectively). Lipolytic activity measured against triolein (18:1), tricaprylin (8:0) and tributyrin (4:0) emulsions was 1.18 +/- 0.12, 4.48 +/- 0.64, and 12.17 +/- 0.88 units (1 unit = 1 mumol free fatty acid released/min per mg protein), respectively. Characterization of the pH optimum for each substrate showed maximum lipolysis at 4.5 for tributyrin, and at 5.5 for tricaprylin and triolein. These results indicate that a lipase which hydrolyzes long-, medium- and short-chain triacylglycerols is secreted by human gastric mucosa. At pH 6.0, the pH of the duodenum, there is appreciable lipolytic activity in the presence of bile salts. This suggests that gastric lipase, in addition to initiating lipolysis in the stomach, might also aid in the digestion of lipids in the duodenum. It remains to be determined whether gastric lipase is distinct from lingual lipase, or is the same enzyme secreted by the lingual serous glands and the gastric mucosa.

Bile Acids and Salts↗

Gastric lipolysis of milk lipids in suckling rats.

Fatty acid composition of the major lipid classes in stomach contents of suckling rats at 1, 5, 10, 17 and 20 days of lactation was compared to that of milk lipids. In milk, 98% of fatty acids were in triacylglycerols at all lactation times. Medium-chain fatty acid concentrations increased from 8% in colostrum to 26% at day 5. Fatty acid composition of stomach acylglycerols at all lactation times was different from that of milk triacylglycerols, containing less medium-chain fatty acids, 8:0 and 10:0. This preferential hydrolysis was also shown by higher concentrations of medium-chain fatty acids in the free fatty acid fraction. The lipolysis of medium-chain fatty acids from triacylglycerols resulted in the appearance of di- and monoacylglycerols with 50-100% higher amounts of 14:0 and 16:0. The similar fatty acid composition of products suggests that considerable lipolysis occurred in stomachs of suckling rats even at 1 day of age. Although there was a 10-fold increase in milk consumption, the extent of lipolysis was similar throughout the suckling period because of a parallel rise in lingual lipase levels.

Animal Population Groups↗

Lipase secretion from dispersed rabbit gastric glands.

We have measured gastric lipase activity in dispersed glands of rabbit stomach by quantitating the hydrolysis of tri[3H]olein. Lipase activity in isolated gastric glands was 200-400 nmol [3H]oleic acid released per milligram dry weight per minute. The percentage of lipase activity released during incubation for 30 min at 37 degrees C under basal conditions was 1.5-4.5%. Lipase release was stimulated by secretagogues: 10 nM cholecystokinin octapeptide (CCK-8) and 100 microM carbachol led to four- to sixfold and two- to threefold higher enzyme secretion, respectively, while histamine had no effect. Carbonyl cyanide m-chlorophenylhydrazone (30 microM) completely inhibited the CCK-8-induced lipase release, indicating that lipase secretion is dependent on mitochondrial oxidative energy; dibutyryl cGMP (1 mM) inhibited 1 nM CCK-8-stimulated but not 100 microM carbachol-stimulated secretion; atropine (1 microM) had the opposite effect. These studies suggest that secretion of lipase from isolated gastric glands is stimulated by at least two receptor mechanisms. These studies show that a lipase that hydrolyzes long-chain triglyceride is secreted by rabbit stomach mucosa and that the secretion of gastric lipase is stimulated by two different receptor mechanisms.

Animals↗

Lipid clearing in premature infants during continuous heparin infusion: role of circulating lipases.

The nature of the lipases released into the circulation during low level continuous infusion of heparin (1 unit/ml total parenteral nutrition) and after bolus heparin injection (10 units/kg) was investigated in a group of 11 low birth weight infants (gestational age 27-34 wk, and postnatal age of 7-26 days) receiving total parenteral nutrition with Intralipid (0.5 g/kg). Hepatic lipase and extra-hepatic lipoprotein lipase were differentiated with the aid of an antibody specific for human hepatic lipase. The data show that continuous low level heparin infusion leads to a constant baseline postheparin lipolytic activity of 0.77 +/- 0.18 mumol free fatty acids released per milliliter serum per hour. Bolus heparin injection leads to peak lipolytic activity levels of 3.77 +/- 0.46 mumol free fatty acids per milliliter serum per hour, 10 min after injection. About two-thirds of the total postheparin lipolytic activity was of the hepatic type during low level continuous infusion or after bolus injection of heparin.

Birth Weight↗

Lipids in milk and the first steps in their digestion.

Human milk contains 3.0% to 4.5% fat. The fat is contained within membrane-enclosed milk fat globules. The core of the globules consists of triglycerides (98% to 99% of total milk fat) whereas the globule membrane (which originates from the mammary secretory cell's Golgi and cell membranes) is composed mainly of phospholipids, cholesterol, and proteins. Milk fat content and composition change during lactation. Whereas the triglyceride level rises, the phospholipid and cholesterol concentrations decrease during the transition from colostrum to mature milk, resulting in an increase in the size of the milk fat globules. Digestion of milk fat depends on the consecutive action of several lipases. The first step is the partial hydrolysis of the milk fat globule core by lingual and gastric lipases in the stomach. Hydrolysis continues in the duodenum, where the bile salt-stimulated lipase of human milk and pancreatic lipase complete the process initiated in the stomach.

Animals↗

Hydrolysis of neutral lipids and phospholipids in the isolated, perfused rat lung.

We have measured the hydrolysis of tri-, di- and monoacylglycerols and of phosphatidylcholine in the lung and have quantitated the incorporation of glyceride and phospholipid fatty acids into lung lipids. Lipolytic activity was studied in the isolated, ventilated, rat lung perfused for 100 min in a recycling system with Krebs-Ringer bicarbonate buffer containing 3% bovine serum albumin, 5.6 mM glucose, and the lipid emulsions. Triacylglycerols were hydrolyzed at significantly (P less than 0.05) lower rates than partial acylglycerols. Hydrolysis of di- and triacylglycerols was significantly lower in lungs of animals given i.v. heparin 60 min prior to death. The incorporation of fatty acids released from acylglycerols was greater into lung neutral fats than into lung phospholipids. Phosphatidylcholine was also hydrolyzed in the isolated perfused lung. The data show that (a) neutral glycerides and phospholipids are hydrolyzed in the isolated, ventilated, perfused rat lung; (b) the hydrolysis of tri- and diacylglycerols is markedly inhibited in lungs isolated from rats given heparin (100 U/kg) 1 h prior to death, whereas the hydrolysis of monoacylglycerol is unaffected by heparin administration, suggesting that tri- and diacylglycerols are hydrolyzed by endothelial lipoprotein lipase, whereas hydrolysis of monoacylglycerol is catalyzed by a separate monoacylglycerol lipase; (c) free fatty acids released by lipoprotein lipase are used by the lung for metabolic needs.

Animals↗