The effects of group and single housing and automated animal monitoring on urinary corticosterone levels in male C57BL/6 mice

Abstract Mice are used extensively in physiological research. Automated home‐cage systems have been developed to study single‐housed animals. Increased stress by different housing conditions might affect greatly the results when investigating metabolic responses. Urinary corticosteroid concentration is considered as a stress marker. The aim of the study was to compare the effects of different housing conditions and an automated home‐cage system with indirect calorimetry located in an environmental chamber on corticosterone levels in mice. Male mice were housed in different conditions and in automated home‐cage system to evaluate the effects of housing and measuring conditions on urine corticosterone levels. Corticosterone levels in single‐housed mice in the laboratory animal center were consistently lower compared with the group‐housed mice. Single‐housed mice in a separate, small animal unit showed a rise in their corticosterone levels a day after they were separated to their individual cages, which decreased during the following 2 days. The corticosterone levels of group‐housed mice in the same unit were increased during the first 7 days and then decreased. On day 7, the corticosterone concentrations of group‐housed mice were significantly higher compared with that of single‐housed mice, including the metabolic measurement protocol. In conclusion, single housing caused less stress when compared with group‐housed mice. In addition, the urine corticosterone levels were decreased in single‐housed mice before the metabolic measurement started. Thus, stress does not affect the results when utilizing the automated system for measuring metabolic parameters like food and water intake and calorimetry

Colonic delivery of nutrients for sustained and prolonged release of gut peptides:a novel strategy for appetite management

Abstract Obesity is one of the major global threats to human health and risk factors for cardiometabolic diseases and certain cancers. Glucagon-like peptide-1 (GLP-1) plays a major role in appetite and glucose homeostasis and recently the USFDA approved GLP-1 agonists for the treatment of obesity and type 2 diabetes. GLP-1 is secreted from enteroendocrine L-cells in the distal part of the gastrointestinal (GI) tract in response to nutrient ingestion. Endogenously released GLP-1 has a very short half-life of <2 min and most of the nutrients are absorbed before reaching the distal GI tract and colon, which hinders the use of nutritional compounds for appetite regulation. The review article focuses on nutrients that endogenously stimulate GLP-1 and peptide YY (PYY) secretion via their receptors in order to decrease appetite as preventive action. In addition, various delivery technologies such as pH-sensitive, mucoadhesive, time-dependent, and enzyme-sensitive systems for colonic targeting of nutrients delivery are described. Sustained colonic delivery of nutritional compounds could be one of the most promising approaches to prevent obesity and associated metabolic diseases by, e.g., sustained GLP-1 release

Inorganic mesoporous particles for controlled α-linolenic acid delivery to stimulate GLP-1 secretion in vitro

Novel treatment methods for obesity are urgently needed due to the increasing global severity of the problem. Gastrointestinal hormones, such as GLP-1 and PYY, are secreted by the enteroendocrine cells, playing a critical role in regulating food intake. Digested nutrients trigger the secretion of these hormones, which have a very short half-life. α-Linolenic acid (αLA) has been shown to stimulate GLP-1 secretion, however, chemical instability and fast uptake in the small intestine hinder its use in body weight management. We developed a novel delivery system based on inorganic mesoporous particles for αLA to increase secretion of gastrointestinal peptides. αLA was loaded to thermally hydrocarbonized porous silicon particles (THCPSi). 47.9 ± 3.84% and 30.7 ± 2.86% of αLA was released during 6 h from 3.0% and 9.2% loading degree (w/w) samples in vitro, respectively. Native αLA (50 µM) significantly increased GLP-1 secretion from enteroendocrine STC-1 and GLUTag cell lines. αLA loaded THCPSi significantly and dose dependently stimulated GLP-1 secretion from STC-1 cells, whereas empty particles did not. We demonstrated in vitro that THCPSi particles have the potential to be used as a controlled delivery system for nutrients such as αLA, increasing GLP-1 secretion. Our results justify further in vivo investigations

Colonic delivery of α-linolenic acid by an advanced nutrient delivery system prolongs glucagon-like peptide-1 secretion and inhibits food intake in mice

Abstract 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