A single oral dose of a polyglucosamine influences the bioavailability of [9-14C]-Oleic acid in adult female Göttingen minipigs

Abstract

BackgroundWorldwide obesity has nearly doubled since 1980 and is a leading risk for global deaths, profoundly affecting morbidity, mortality, health-care costs, and professional and personal quality of life. Treatment of obesity and its consequences include lifestyle intervention, pharmacotherapy, and bariatric surgery. Polyglucosamines have been proposed as an alternative strategy for treating obesity, by reducing the amount of absorbed fat through interaction with dietary fat through various mechanisms. The objective of this study is to investigate the influence of polyglucosamine on the bioavailability of the model compound [9-14C]-oleic acid in female Göttingen minipigs.MethodThe study consisted of two treatment groups, each consisting of six adult female Göttingen minipigs with a catheterized vena jugularis to enable frequent blood sampling. One group served as the untreated group (control) and the other group was pre-treated with 2 tablets of 500 mg formoline L112. After 30 min, all animals were dosed orally with [9-14C]-oleic acid. Excreta and blood samples were collected for analysis of radioactivity from 48 h pre-dose up to 144 h post-dosing. At sacrifice, the liver and contents of the gastrointestinal tract were collected for radioanalysis.ResultsUpon treatment with polyglucosamine (formoline L112), the Tmax of [14C]-oleic acid in plasma was shifted from 4 to 16 h, and the Cmax decreased significantly from 14.1 μg/g to 3.3 μg/g. In addition, upon treatment with polyglucosamine the internal exposure to [14C]-oleic acid as reflected by the area under the curve during the 0–12 h post-dose time interval (AUC0-12h), is significantly decreased to 32.9 % of the plasma value of [14C]-oleic acid in untreated animals. Even up to 24 h post-dose, the AUC0-24h is significantly decreased to 50.7 % of the plasma value in untreated animals and this significant effect is prolonged up to 60 h post-dose.ConclusionsThis study shows that treatment with polyglucosamine (formoline L112) reduces (as judged by Cmax & AUC) and delays (as judged by Tmax) fat absorption from the gastrointestinal tract into the systemic circulation and limits peak exposure to free fatty acids which may contribute to a more beneficial condition in overweight humans.

Body Weight Reduction with L112: Review of Double Blind Randomized Controlled Clinical Trials

“…This is an important characteristic, since the omental fat is one of the causes of the inflammatory processes that are known to facilitate the tendency towards type II diabetes and cardiovascular diseases. This mechanism of the reduction of fat absorption was also determined experimentally, using the labelled oleic acid as marker [6]. It was clearly shown that oleic acid absorption was reduced by the administration of PG.…”

Long-Term Treatment of Overweight and Obesity with Polyglucosamine (PG L112): Randomized Study Compared with Placebo in Subjects after Caloric Restriction

“…PG is a low-MW chitosan used in fixed combinations with ascorbic and tartaric acids. Pharmacologic studies have shown that PG reduces BW and increases the glucose elimination in feces ( 10 ), and the concomitant oral administration of [9- 14 C]oleic acid in mini pigs has been found to lead to a consistent decrease in fecal fat content ( 11 ). Gut bacteria seem to use the fats bound to PG and released in the large intestine as a source of energy, thus helping to restrict caloric intake and reduce steatorrhea ( 9 , 10 ).…”

Meta-analysis of studies on body weight and cholesterol reduction using the chitosan derivative polyglucosamine L112

“…The standardized PG has been shown in preclinical studies to reduce the absorption of labelled (C14) oleic acid in Göttingen minipigs, to reduce the BW and increase fat excretion in rats and to increase the acetate excretion in rats [16][17][18]. This last aspect is considered important for the satiety, since acetate was shown to stimulate the grehlin secretion inducing hyperphagia and related sequelae [19].…”