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      The modulation of pancreatic lipase activity by alginates

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          Highlights

          • Certain alginates are effective inhibitors of pancreatic lipase.

          • The level of lipase inhibition by alginates is related to the structure of the polymer.

          • High guluronate alginates achieve greater lipase inhibition than high mannuronate.

          • Alginates have the potential to be a well-tolerated obesity treatment.

          Abstract

          Alginates are comprised of mannuronic (M) and guluronic acid (G) and have been shown to inhibit enzyme activity. Pancreatic lipase is important in dietary triacylglycerol breakdown; reducing pancreatic lipase activity would reduce triacylglycerol breakdown resulting in lower amounts being absorbed by the body.

          Lipase activity in the presence of biopolymers was assessed by enzymatic assay using natural and synthetic substrates. Alginate inhibited pancreatic lipase by a maximum of 72.2% (±4.1) with synthetic substrate (DGGR) and 58.0% (±9.7) with natural substrate. High-G alginates from Laminaria hyperborea seaweed inhibited pancreatic lipase to a significantly higher degree than High-M alginates from Lessonia nigrescens, showing that inhibition was related to alginate structure.

          High-G alginates are effective inhibitors of pancreatic lipase and are used in the food industry at low levels. They could be included at higher levels in foods without altering organoleptic qualities, potentially reduce the uptake of dietary triacylglycerol aiding in weight management.

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          Most cited references27

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          The digestion of dietary triacylglycerols.

          H Mu (2004)
          Dietary triacylglycerols (TAGs) are the major lipid components in the human diet and they are carriers of energy as well as important fatty acids. Many factors affect the digestion and absorption of TAGs. Evidence is accumulating that, in addition to the overall fatty acid profile, the TAG structure and the species composition are of importance when considering the nutritional effects of a dietary fat. There is good evidence that in addition to its short-term effects in the intestine on absorption of fatty acids the TAG structure also has long-term effects resulting from differences in the profile of absorbed fatty acids. Observations on the different atherogenic potential of dietary fats have given us a clear indication of the importance of the TAG structure for absorption of saturated fatty acids. In this context, one may focus on the effects of the structure of dietary fats as such, or one may speculate additionally on the possibilities of modifying the structure of fats to affect their absorption and the distribution of the fatty acids in the body after digestion and uptake. In this review we will summarize diverse aspects of TAG digestion and absorption, as well as the influences of the fatty acid composition and the intramolecular structure of dietary TAGs on their digestion and absorption.
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            Inhibition of pancreatic lipase in vitro by the covalent inhibitor tetrahydrolipstatin.

            Tetrahydrolipstatin inhibits pancreatic lipase from several species, including man, with comparable potency. The lipase is progressively inactivated through the formation of a long-lived covalent intermediate, probably with a 1:1 stoichiometry. The lipase substrate triolein and also a boronic acid derivative, which is presumed to be a transition-state-form inhibitor, retard the rate of inactivation. Therefore, in all probability, tetrahydrolipstatin reacts with pancreatic lipase at, or near, the substrate binding or active site. Tetrahydrolipstatin is a selective inhibitor of lipase; other hydrolases tested were at least a thousand times less potently inhibited.
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              Retrospective population-based analysis of the dose-response (fecal fat excretion) relationship of orlistat in normal and obese volunteers.

              Orlistat, an inhibitor of gastrointestinal lipases, limits the absorption of ingested fat and could become a potential treatment for obesity. This analysis was performed to elucidate the relationship between orlistat dose and intensity of inhibition of dietary fat absorption (assessed by measuring fecal fat excretion). In 11 phase I double-blind, placebo-controlled, parallel-group randomized studies, a total of 171 subjects received oral daily doses that ranged from 30 to 1200 mg orlistat or matching placebo three times a day for 9 to 10 days. The results of the daily mean fecal fat excretion percentage (relative to ingested fat) were correlated to the orlistat daily dose. A simple maximum-effect model that included a basal value was used to fit the dose-response relationship for all evaluable subjects. The mean maximum percentage of ingested fat excreted in the feces was approximately 32% during orlistat administration compared with 5% during placebo administration. The orlistat daily dose that produced 50% of the maximum effect was 98 mg/day. The model-fitting suggests the existence of a steep portion of the dose-response curve up to approximately 400 mg/day, with a subsequent tendency to plateau at higher doses. Such an analysis was instrumental in identifying appropriate doses to be used in therapeutic trials for weight loss in obese patients.
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                Author and article information

                Contributors
                Journal
                Food Chem
                Food Chem
                Food Chemistry
                Elsevier Applied Science Publishers
                0308-8146
                01 March 2014
                01 March 2014
                : 146
                : 100
                : 479-484
                Affiliations
                [a ]Institute for Cell and Molecular Biosciences, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne, Tyne and Wear NE2 4HH, UK
                [b ]Technostics Ltd., Daisy Building (2nd floor), Castle Hill Hospital, Castle Road, Hull HU16 5JQ, UK
                Author notes
                [* ]Corresponding author. Tel.: +44 (0)191 222 5013; fax: +44 (0)191 222 7424. matthew.wilcox@ 123456ncl.ac.uk
                [1]

                Present address: Food & Human Nutrition, Newcastle University (Singapore), Nanyang Polytechnic Campus, Singapore.

                Article
                S0308-8146(13)01340-X
                10.1016/j.foodchem.2013.09.075
                4018670
                24176371
                12f14a5c-4153-414e-a3a7-3978863eb797
                © 2013 The Authors

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/).

                History
                : 2 May 2013
                : 4 July 2013
                : 12 September 2013
                Categories
                Article

                Food science & Technology
                alginate,lipase,inhibition,obesity,weight management
                Food science & Technology
                alginate, lipase, inhibition, obesity, weight management

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