Chloroplast membranes retard fat digestion and induce satiety: effect of biological membranes on pancreatic lipase/co-lipase

Abstract

Human obesity is a global epidemic, which causes a rapidly increased frequency of diabetes and cardiovascular disease. One reason for obesity is the ready availability of refined food products with high caloric density, an evolutionarily new event, which makes over-consumption of food inevitable. Fat is a food product with high caloric density. The mechanism for regulation of fat intake has therefore been studied to a great extent. Such studies have shown that, as long as fat stays in the intestine, satiety is promoted. This occurs through the fat-released peptide hormones, the best known being CCK (cholecystokinin), which is released by fatty acids. Hence, retarded fat digestion with prolonged time for delivery of fatty acids promotes satiety. Pancreatic lipase, together with its protein cofactor, co-lipase, is the main enzymatic system responsible for intestinal fat digestion. We found that biological membranes, isolated from plants, animals or bacteria, inhibit the lipase/co-lipase-catalysed hydrolysis of triacylglycerols even in the presence of bile salt. We propose that the inhibition is due to binding of lipase/co-lipase to the membranes and adsorption of the membranes to the aqueous/triacylglycerol interface, thereby hindering lipase/co-lipase from acting on its lipid substrate. We also found that chloroplast membranes (thylakoids), when added to refined food, suppressed food intake in rats, lowered blood lipids and raised the satiety hormones, CCK and enterostatin. Consequently, the mechanism for satiety seems to be retardation of fat digestion allowing the fat products to stay longer in the intestine.

The effect of heat treatment of thylakoids on their ability to inhibit in vitro lipase/co-lipase activity

“…In a series of previous studies we have found that thylakoid membranes, the photosynthetic membrane in plant cells, inhibit pancreatic lipase/co-lipase in a dose-dependent way in vitro, an effect confirmed both in animal studies on rat 12 and mice 13 as well as in human studies 14,15 .…”

Chloroplast thylakoids reduce glucose uptake and decrease intestinal macromolecular permeability

“…The thylakoid membranes are negatively charged at neutral pH, with an isoelectric point of 4·7 (27) . Thylakoids expose both hydrophilic and hydrophobic surface groups and have also been found to adsorb onto the surface of oil droplets and form stable oil-in-water emulsions (4,28) . Due to the large size of the thylakoid surface the number of exposed groups per thylakoid particle is large so that, even if the individual group interactions are weak, the sum of them will be large.…”

“…The swelling and unfolding may allow the thylakoids to cover a larger surface of the intestine. Native thylakoids have an area of about 2 m 2 /mg chlorophyll (4,15) , and the exposed area may increase significantly upon the unfolding caused by bile salts and fatty acids. It thus appears that this thylakoid network is responsible for the decreased passage through the intestinal wall.…”

“…This retardation in turn stimulates the release of satiety hormones, such as cholecystokinin (4,5) and leptin (6) , while reducing the hunger hormones ghrelin and insulin (6) . The long-term effect of thylakoid administration was thus a reduced food intake and body weight, as demonstrated both in mice (5) and in rat models (4) . To our surprise, a reduction in blood glucose levels after oral administration of thylakoids was also observed (5) .…”

“…chloroplast membranes from green leaves, retard fat digestion both in vitro and in vivo (4) . This retardation in turn stimulates the release of satiety hormones, such as cholecystokinin (4,5) and leptin (6) , while reducing the hunger hormones ghrelin and insulin (6) . The long-term effect of thylakoid administration was thus a reduced food intake and body weight, as demonstrated both in mice (5) and in rat models (4) .…”