Biomedical subjects
M Hamosh
Publications and source records attributed to M Hamosh.
Uptake of blood triglyceride by various tissues.
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Lipoprotein lipase activity during pregnancy and lactation.
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Lipoprotein lipase activity in guinea pig and rat milk.
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Lipoprotein lipase activity of adipose and mammary tissue and plasma triglyceride in pregnant and lactating rats.
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Effects of acute hypertrophy on the contractile properties of skeletal muscle.
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The role of lingual lipase in neonatal fat digestion.
Lingual serous glands (von Ebner) contain a potent lipase that hydrolyses triglycerides to a mixture of partial glycerides (di- and monoglycerides), glycerol and free fatty acids. Studies in man and in rat have shown that similar lipolytic activity is present in oesophageal and gastric aspirates and suggest that the intragastric digestion of dietary fat is initiated by lingual lipase. In the rat the lingual serous glands are initiated in 19- to 20-day fetuses; lipase activity is first detected in 20-day-old fetuses and increases 14-fold by birth. The data suggest that in the fetus lipase activity originates predominantly in the serous demilune cells of mucous glands whereas after birth the enzyme is synthesized and stored in the rapidly differentiating serous glands. In man lipolytic activity is present in gastric aspirates as early as 26 weeks of gestational age. Our studies suggest that the lipolytic activity has characteristics similar to those of adult human and rat lingual lipase; the enzyme is present in the oesophageal pouch of infants with oesophageal atresia indicating that in infants, as in adults, it probably originates in the lingual serous glands. Since the enzyme is active in the absence of bile salts and has a low pH optimum it is ideally suited to act in the stomach and probably compensates in the premature for low pancreatic lipase activity. The lipolytic activity could be important, not only in the digestion of dietary fat, but in helping to overcome the temporary bile salt deficiency and to solubilize dietary fat through the formation of amphiphilic reaction products.
Effect of tobacco smoke on the metabolism of rat lung.
The authors have studied the effect of cigarette smoke on the uptake and metabolism of 3H-palmitate, 3H-leucine, U14C-glucose and 14C-glucosamine utilizing slices of rat lung. The rats were exposed daily for 30 days to University of Kentucky research cigarettes (brands 1A1 or 1R1) in the Walton smoking machine. One group of rats served as intact controls and another were introduced into the machine, but were not exposed to smoke. All animals were weight-matched at the beginning of the experiment (180 +/- 5 g); machine control rats gained 25% less weight, 1A1-exposed rats 40%; and 1R1-exposed rats 26-40% less than controls. Exposure to tobacco smoke had no effect on palmitate uptake and synthesis of phospholipids; exposure to 1A1 cigarettes caused a 25% increase in 14CO2 production and a 30% higher incorporation of glucose into lipids. Exposure to 1R1 cigarettes had no effect on glucose metabolism. Protein synthesis was 30% lower in 1R1-exposed rats and glycoprotein synthesis increased two-fold in both 1A1 and 1R1 exposed rats.
Lipid composition of prepartum human mammary secretion and postpartum milk.
Changes in lipid composition of mammary secretions of five women were studied at two prepartum periods and compared with composition of colostrum, transitional, and mature human milk. Fat content was approximately 1 g/dl during early (-42.0 days before parturition) and late (-9.5 days) prepartum periods and increased to 3-4 g/dl in colostrum (3.0 days post partum), transitional (7.2 days), and mature milk (56.2 days). Most of the lipid present was triglyceride either pre- (93%) or post- (97%) partum. All fat globule core lipids, with the exception of 1,3-diglycerides, increased from prepartum concentrations to levels usually found in milk. Prepartum secretions contained higher amounts of the membrane components, phospholipid (3.2 g/dl), cholesterol (2.3 g/dl), and cholesteryl ester (1.1 g/dl), which declined postpartum to 0.65, 0.37, and 0.09 g/dl, respectively. Thus, the content of core lipids exhibited an opposite pattern to the content of membrane lipids pre- and postpartum. With regard to synthesis of fatty acids, prepartum secretory mechanisms appeared to be very similar to those occurring postpartum since fatty acid composition of prepartum secretions closely resembled that of postpartum milk.
Comparison of the cholesteryl ester composition of human milk from preterm and term mothers.
Milk was obtained on postpartum days 2-3 (colostrum) and days 7, 21, 42, and 84 from mothers of 18 very premature (VPT, 26-30 weeks gestational age), 28 premature (PT, 31-36 weeks), and 6 term (T, 37-40 weeks) infants. Lipids were extracted in chloroform-methanol and analyzed by thin-layer (TLC) and gas liquid chromatography (GLC). Fatty acid composition of cholesteryl esters was determined by GLC after isolation of cholesteryl esters by preparative TLC and preparation of methyl esters of the constituent fatty acids. As lactation progressed, amounts of total cholesterol and cholesteryl esters declined. Cholesteryl esters decreased from about 5 mg/dl in colostrum to 1 mg/dl in mature milk. The cholesteryl esters of colostrum from mothers of premature infants were different in fatty acid composition from those of term infants. Proportions of medium-chain saturated fatty acids (12:0, 14:0, 16:0) of preterm colostrum (VPT and PT) were considerably lower than in term colostrum: 23% of total fatty acids versus 35%. Proportions of 18:3, 20:3, and 20:4 of VPT (5.6%) and PT (6.2%) colostrum were considerably higher than T colostrum (1.8%). The fatty acid composition of cholesteryl esters of VPT, PT, and T milk was relatively similar at all subsequent lactation periods. Fatty acids esterified with cholesterol in weight percents were as follows: 10:0, 0.7; 12:0, 2.6; 14:0, 2.3; 16:0, 11.4; 16:1, 5.0; 18:0, 8.8; 18:1, 32.9; 18:2, 30.6; 18:3, 1.7; 20:3, 0.9; and 20:4, 1.8. Unsaturated fatty acids contributed 73 wt % of fatty acids in cholesteryl esters, which is considerably higher than in milk triglycerides. The greatest difference occurred in 18:2 content, which was 30.6% in cholesteryl esters and only 13.0% of total fatty acids in milk. Results suggest that unsaturated fatty acids are associated preferentially with the cholesteryl ester fraction and that the fatty acid composition of cholesteryl esters differs from the composition of total milk lipid.
Diurnal and within-feed variations in lipase activity and triglyceride content of human milk.
This study examined the diurnal and within-feed variations in the two lipases of human milk, bile-salt-stimulated lipase (BSSL) and lipoprotein lipase (LPL). In addition, all milks were also analyzed for triglyceride content. As compared to BSSL, LPL activity was more variable both among mothers and among different samples from the same mother (largest variation, 0-2.8 U/ml milk). The only significant variation in lipase activity was in LPL activity during a 24-h period (0.96 +/- 0.113, 0.52 +/- 0.21, and 0.57 +/- 0.092 U/ml milk at 0801-1600, 0001-0800, and 1601-2400 h, respectively) (p less than 0.05). Triglyceride content showed no significant diurnal variation but did increase significantly during a single feeding (31 +/- 9.4, 52 +/- 11.7, and 72 +/- 14.8, mumoles triglyceride/ml milk for fore-, mid-, and hind-milks, respectively) (p less than 0.05). There was no correlation between either LPL or BSSL activity and triglyceride content of the milks. Our data indicate that milk obtained for banking or research purposes will contain similar levels of BSSL activity irrespective of diurnal or within-feed timing of milk collections.
Total parenteral nutrition with intralipid in premature infants receiving TPN with heparin: effect on plasma lipolytic enzymes, lipids, and glucose.
Plasma lipolytic activity (lipoprotein lipase and hepatic lipase), free fatty acids (FFA), triglycerides, cholesterol, and glucose levels were measured in 21 premature infants [gestational age 26-37 weeks (mean +/- SEM 30.4 +/- 0.63 weeks), aged 1-8 days (mean +/- SEM 3.00 +/- 0.35 days)]. All infants were maintained on total parenteral nutrition with heparin (1 U/ml) and were given Intralipid, 1, 2, and 3 g/kg/day, over 15 h on days 1, 2, and 3, respectively. Blood samples were drawn before and at the end of Intralipid administration. Baseline plasma lipolytic activity, before the start of lipid infusion, was 1.54 +/- 0.24 U/ml (1 U = 1 mumol [3H]oleic acid released from tri[3H]olein/h). Lipolytic activity increased after lipid infusion to 4.04 +/- 0.96, 4.32 +/- 0.63, and 6.09 +/- 1.00 U/ml on days 1, 2, and 3 of the study. Hepatic lipase amounted to 38-47% of total lipolytic activity. During the 3 days of lipid infusion, there were dose-dependent increases in plasma FFA, triglyceride, and cholesterol. Whereas FFA and triglyceride concentrations returned to prelipid infusion levels 9 h after stopping the infusion of Intralipid, 1, 2, or 3 g/kg, there was a cumulative increase in plasma cholesterol and glucose concentrations. The close correlation between FFA concentrations and plasma lipolytic activity (r = 0.655, p less than 0.001) suggests considerable intravascular lipolysis. The positive correlation between plasma FFA and triglycerides (r = 0.632, p less than 0.001) and FFA and cholesterol (r = 0.582, p less than 0.001) indicate, however, that intravascular lipolysis does not prevent the lipemia associated with Intralipid infusion to low birth weight infants.(ABSTRACT TRUNCATED AT 250 WORDS)
Bile salt-stimulated lipase of human milk: characteristics of the enzyme in the milk of mothers of premature and full-term infants.
Human milk contains a lipase (bile salt-stimulated lipase) that is considered to have an important role in infant fat digestion. In this study we compared the characteristics of bile salt-stimulated lipase activity in milk samples from mothers delivering prematurely (26-30 and 31-37 weeks of gestation) and in milk from mothers delivering at term (38-42 weeks of gestation). Preterm milks were collected at day 1-5 and during week 6 of lactation. Term milks were collected during week 6 of lactation. The characteristics of the enzyme (kinetics, enzyme concentration, pH optimum, and pH stability, effects of bile salt structure and concentration, eserine inhibition) were identical regardless of length of pregnancy or duration of lactation. Bile salt-stimulated lipase had a neutral to alkaline pH optimum (pH 7.3-8.6), was stable for 1 h at a wide pH range (pH 3.1-8.6), was active only in the presence of primary bile salts, and was inhibited by eserine. The data indicate that, following parturition at as early as 26 weeks of gestation, the mammary glands synthesizes bile salt-stimulated lipase with identical characteristics as does the mammary gland after a full-term pregnancy.
Does infant nutrition affect adiposity and cholesterol levels in the adult?
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Ultrasonic homogenization of expressed human milk to prevent fat loss during tube feeding.
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Lingual and gastric lipases.
The 1973 discovery of lingual lipase, which is secreted by lingual serous glands and hydrolyzes medium- and long-chain triglycerides in the stomach, has renewed interest in the gastric phase of fat digestion. In humans, lipase is present in the serous (von Ebner) glands of the tongue, where it is localized in zymogen granules. In the stomach, the highest lipase activity is in the body. By immunocytochemistry, gastric lipase is confined to the chief cells of the fundic mucosa and is colocalized with pepsin. Human lipase purified from lingual serous glands or gastric juice has a MW of 45k to 51K but tends to aggregate (MW 270-300K and 500K) and is highly hydrophobic. Secretion of gastric lipase appears to be stimulated by at least two receptor mechanisms. It has been suggested that the products of gastric lipolysis maintain the sterility of the gastrointestinal tract. These enzymes are essential for the digestion of milk fat in the newborn because, contrary to other digestive lipases (pancreatic or milk digestive lipase), lingual and gastric lipases can penetrate into the milk fat globule and initiate the digestive process. Lingual and gastric lipase activity has been found in subjects with cystic fibrosis and appears to continue in the upper small intestine in these patients, perhaps replacing some of the missing pancreatic lipase. It is possible that lingual and gastric lipase supplements would be more effective in preventing steatorrhea in these patients than are the pancreatic enzyme supplements now given. The same therapeutic utility might be obtained in patients with alcoholic pancreatic insufficiency.