The biochemistry of algal bioactives : their role in modulation of digestive processes

Abstract

Obesity is a serious global threat to public health causing serious chronic metabolic diseases. The drug Orlistat has been used for obesity treatment; however, orlistat causes unpleasant gastrointestinal side-effects. Recent research has investigated bioactive compounds from seaweeds, like alginate, as pancreatic lipase inhibitors to modulate fat digestion and reduce caloric intake. Previous work has shown that certain alginates can inhibit pancreatic lipase activity in vitro by up to 72%. The aim of this thesis is to investigate the effect of alginate on lipase activity in vitro, using three different approaches: turbidimetric assay, a kinetic assay and a synthetic model gut system. The turbidimetric assay for pancreatic lipase showed alginates can inhibit pancreatic lipase, with the level of inhibition depending on alginate structure and concentration. Alginate with a high content of guluronate residues can inhibit pancreatic lipase activity more than alginate rich in mannuronate residues. Kinetic analysis showed that alginates act as mixed inhibitors that can bind to both the free enzyme and the enzyme-substrate complex. Alginate passed through the gastric phase of the synthetic model gut reduced glyceryl trioctanoate digestion, but not the digestion of olive or sunflower oil. However, alginate added at the small intestinal phase reduced olive oil digestion. The regulatory effect of alginate was affected by gastric pH resulting in gel formation and precipitation, reducing or preventing the release of free alginate and reducing lipase inhibition. Alginate bread was digestible within the synthetic model with most alginate release occurring in the small intestinal phase. Alginate incorporated into bread did not reduce fat digestion, which may be due to alginate fragmentation resulting from high temperatures during the cooking process. The capacity of unfragmented alginates to inhibit pancreatic lipase activity in vitro supports future investigations of alginate in vivo as a pancreatic lipase inhibitor to reduce fat digestion and absorption and hence, treat obesity.