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- Sternby, Berit, et al.
(författare)
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Degree of in vivo inhibition of human gastric and pancreatic lipases by Orlistat (Tetrahydrolipstatin, THL) in the stomach and small intestine.
- 2002
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Ingår i: Clinical Nutrition. - : Elsevier BV. - 1532-1983 .- 0261-5614. ; 21:5, s. 395-402
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Orlistat, a lipase inhibitor, strongly inhibits the activities of all gastric/pancreatic lipases except pancreatic phospholipase A(2)in vitro. In clinical use, for obesity treatment, it induces a variable degree of weight loss and steatorrhoéa. The aim of this study was to examine the degree of in vivo inhibition of individual gastric/pancreatic lipases by Orlistat in man, when given as a capsule or mixed into a test meal in the form of an optimal substrate for the lipases.METHODS: Twelve male volunteers were intubated twice with a triple lumen nasal-gastric-duodenal tube and were given a balanced test meal with or without 60mg Orlistat. Three conditions were compared: (a) Orlistat given as a capsule with the meal, (b) Orlistat mixed into the test meal before ingestion, and (c) test meal without Orlistat. Samples were collected at six 30min intervals, from stomach, mid-duodenum, and ligament of TreitY. Activities and immune-reactive masses of gastric lipase, pancreatic lipase, carboxyl ester lipase, colipase, and mass of non-polar lipid classes were determined.RESULTS: In vivo effects on the enzyme activities were more pronounced when Orlistat was mixed with the meal than when given as a capsule (7%, 10%, 1% vs 49%, 54%, 34% of normal activity), respectively. Despite efficient inhibition of the lipases, an extensive hydrolysis of the emulsified lipids of the test meal occurred. Orlistat did not affect the immune-reactive amounts of lipases.CONCLUSIONS: Orlistat causes a pronounced in vivo inhibition of gastric and pancreatic lipases in humans. The mixing with the substrate and the fact that little residual lipase activity is necessary to hydrolyse optimally emulsified lipids are likely to be limiting factors for the effect of the drug in clinical practice.
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| 2. |
- Zhou, Li, et al.
(författare)
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Hydrolysis of the cubic liquid-crystalline phase of glyceryl monooleate by human pancreatic lipases
- 2002
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Ingår i: Lipid and Polymer-Lipid Systems (Progress in Colloid and Polymer Science). - 0340-255X. - 9783540430018 ; 120, s. 92-98
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Konferensbidrag (refereegranskat)abstract
- Glyceryl monooleate (GMO) and other unsaturated long-chain monoglycerides show peculiar phase behaviour characterised by the presence of one or more cubic liquid-crystalline phases. In the present study, hydrolysis of cubic lipid-water phases formed by GMO were determined. Human pancreatic carboxyl ester lipase (CEL), colipase-dependent lipase with colipase, human duodenal contents and rat pancreas homogenate were added and the release of free oleic acid from GMO was determined. It was found that pancreatic enzymes hydrolyse GMO cubic lipid-water phases in vitro. In the presence of concentrations of sodium taurocholate, sodium taourodeoxycholate or sodium glycocholate, above 3 mM, the hydrolysis by pancreatic enzymes was stimulated. The optimal pH for the hydrolysis of GMO by CEL was 7.5-8.5, by colipase-dependent lipase 6-9 with a peak at 6.5 and by rat pancreas homogenate 6-8.5 with a peak at 7.3. The hydrolysis of GMO with human duodenal content was slow but increased with time. These results indicated that pancreatic enzymes hydrolyse GMO in cubic lipid-water phases. The hydrolysis is effected by pH and the concentration of bile salts.
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