Colonic Delivery of α‐Linolenic Acid by an Advanced Nutrient Delivery System Prolongs Glucagon‐Like Peptide‐1 Secretion and Inhibits Food Intake in Mice

SCOPE: Nutrients stimulate the secretion of glucagon‐like peptide‐1 (GLP‐1), an incretin hormone, secreted from enteroendocrine L‐cells which decreases food intake. Thus, GLP‐1 analogs are approved for the treatment of obesity, yet cost and side effects limit their use. L‐cells are mainly localized in the distal ileum and colon, which hinders the utilization of nutrients targeting GLP‐1 secretion. This study proposes a controlled delivery system for nutrients, inducing a prolonged endogenous GLP‐1 release which results in a decrease food intake. METHODS AND RESULTS: α‐Linolenic acid (αLA) was loaded into thermally hydrocarbonized porous silicon (THCPSi) particles. In vitro characterization and in vivo effects of αLA loaded particles on GLP‐1 secretion and food intake were studied in mice. A total of 40.4 ± 3.2% of loaded αLA is released from particles into biorelevant buffer over 24 h, and αLA loaded THCPSi significantly increased in vitro GLP‐1 secretion. Single‐dose orally given αLA loaded mesoporous particles increased plasma active GLP‐1 levels at 3 and 4 h and significantly reduced the area under the curve of 24 h food intake in mice. CONCLUSIONS: αLA loaded THCPSi particles could be used to endogenously stimulate sustain gastrointestinal hormone release and reduce food intake.