Effect of Gum Acacia on the Intestinal Bioavailability of n-3 Polyunsaturated Fatty Acids in Rats.

Lipid emulsification is a technique that is being explored for improving the bioavailability of omega 3 (n-3) long chain (LC) fatty acid (FA). The nature of the emulsifiers can differently impact the lipid bioavailability via a modification of the lipolysis step. Among natural emulsifiers, gum acacia (GA), an indigestible polysaccharide, provides protective encapsulation of n-3 by forming a specifically crown-like shape around lipid drops, which could also impact the digestion step. Despite the interest in lipolysis rate, the impact of GA on lipid bioavailability has never been explored in a complete physiological context. Thus, we followed in a kinetics study the n-3 bioavailability in rat lymph, orally administered DHA-rich oil, formulated based on GA compared to the bulk phase form of the oil. The AUC values were significantly improved by +121% for total TG and by 321% for n-3 PUFA, specifically for EPA (+244%) and for DHA (+345%). Benefits of GA have also been related to the transport of FA in lymph, which was 2 h earlier (Tmax = 4 h), compared to the Tmax (6 h) obtained with the bulk phase oil. All the data showed that GA is one of the most favorable candidates of natural emulsifiers to improve n-3 bioavailability and their rate of absorption for health targets.

Slowing down fat digestion and absorption by an oxadiazolone inhibitor targeting selectively gastric lipolysis.

Based on a previous study and in silico molecular docking experiments, we have designed and synthesized a new series of ten 5-Alkoxy-N-3-(3-PhenoxyPhenyl)-1,3,4-Oxadiazol-2(3H)-one derivatives (RmPPOX). These molecules were further evaluated as selective and potent inhibitors of mammalian digestive lipases: purified dog gastric lipase (DGL) and guinea pig pancreatic lipase related protein 2 (GPLRP2), as well as porcine (PPL) and human (HPL) pancreatic lipases contained in porcine pancreatic extracts (PPE) and human pancreatic juices (HPJ), respectively. These compounds were found to strongly discriminate classical pancreatic lipases (poorly inhibited) from gastric lipase (fully inhibited). Among them, the 5-(2-(Benzyloxy)ethoxy)-3-(3-PhenoxyPhenyl)-1,3,4-Oxadiazol-2(3H)-one (BemPPOX) was identified as the most potent inhibitor of DGL, even more active than the FDA-approved drug Orlistat. BemPPOX and Orlistat were further compared in vitro in the course of test meal digestion, and in vivo with a mesenteric lymph duct cannulated rat model to evaluate their respective impacts on fat absorption. While Orlistat inhibited both gastric and duodenal lipolysis and drastically reduced fat absorption in rats, BemPPOX showed a specific action on gastric lipolysis that slowed down the overall lipolysis process and led to a subsequent reduction of around 55% of the intestinal absorption of fatty acids compared to controls. All these data promote BemPPOX as a potent candidate to efficiently regulate the gastrointestinal lipolysis, and to investigate its link with satiety mechanisms and therefore develop new strategies to "fight against obesity".