Novel Delivery System for α‐Linolenic Acid for GLP‐1 Release and Weight Management

Abstract

BackgroundNovel strategy and treatment methods for obesity and metabolic diseases are urgently needed. Various nutrients such as carbohydrate, fat, and proteins are involved in meal‐stimulated Glucagon like peptide‐1 (GLP‐1) release. GLP‐1 plays critical roles in maintaining euglycemia and controlling appetite, however it has a very short half‐life. Hence, novel delivery system for nutritional compounds could be potential approach to prolong GLP‐1 release. For that, Porous Silicon (PSi) is a promising carrier due to its biodegradable and non‐toxic nature. The objective of this study was investigating if PSi could be used as a delivery system for nutritional compounds to stimulate GLP‐1 release and thereby reduce food intake. We hypothesize that α‐Linolenic acid (αLA) encapsulated PSi particles will prolong the stimulation of enteroendocrine signals and inhibit food intake.MethodsαLA was loaded into PSi particles by impregnation method. For release experiment, αLA loaded PSi particles were incubated in Simulated Gastric Fluid (SGF, pH 1.2 PBS + 3.2 mg/ml pepsin) for 2h and in Simulated Intestinal Fluid (SIF, pH 4.8 PBS) for 2h, then SIF (pH 7.4 PBS + 1.6 mg/ml pancreatin) for up to 20 h at 37 °C. In vitro GLP‐1 secretion with PSi particles with or without αLA was studied in enteroendocrine STC‐1 cells. The cells were incubated with the supernatant from the release experiments for 1h and GLP‐1 level was measured by ELISA kit. The in vivo effect of αLA and αLA loaded PSi were investigated in C57/BL6 male mice (10 weeks old), housed individually with free access to food (commercial rodent chow) and tap water. The mice were orally gavage with αLA loaded PSi or empty particle suspended in vehicle along with positive controls at single dose 1h before the light off. The following samples were used: control, αLA (100, 200 and 500 mg/kg B.W.), 20% αLA loaded PSi (equivalent amount of αLA 200 mg/kg B.W.), and empty PSi. Food and water intake were monitored for 48 hours in an automated monitoring system.ResultsαLA was successfully loaded into PSi particles with a high loading degree (20% w/w). 26.7 ± 4.0% of loaded αLA was released from particles into SGF during 2h incubation period, and 50.0 ± 5.0% was released into SIF in 24h. The release of αLA from PSi was controlled by diffusion. αLA and αLA loaded PSi particles significantly increased GLP‐1 secretion from STC‐1 cells. αLA in a dose of 200 and 500 mg/kg B.W. significantly inhibited food intake compared to control. In addition, αLA loaded PSi significantly reduced food intake, while empty PSi did not. The area under curve of 24h food intake/body weight in αLA 200 mg/kg B.W. and αLA loaded PSi were 18.1% and 15.2% lower than control, respectively.ConclusionPSi particles have a high loading efficiency and release the loaded compounds in a sustained manner, indicating that PSi could be used as a carrier for delivering nutritional compounds to distal part of the intestine. Our results also suggest that αLA loaded PSi particles could be used for weight management via stimulating the secretion of gastrointestinal hormones.