A novel system for delivery of nutritional compounds to regulate appetite

Thesis event information

Date and time of the thesis defence

Place of the thesis defence

Auditorium F101 of the Faculty of Biochemistry and Molecular Medicine (Aapistie 7)

Topic of the dissertation

A novel system for delivery of nutritional compounds to regulate appetite

Doctoral candidate

Master of science Remi Kamakura

Faculty and unit

University of Oulu Graduate School, Faculty of Medicine, Research Unit of Biomedicine

Subject of study

Physiology

Opponent

Professor Jens Juul Holst, University of Copenhagen

Custos

Professor Karl-Heinz Herzig, University of Oulu

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A novel system for delivery of nutritional compounds to regulate appetite

The increasing number of obese and overweight people is a serious global health concern. Obesity is known as a major risk factor for cardiovascular diseases, type 2 diabetes mellitus, and metabolic disorders. Therefore, novel treatments and preventions methods for obesity and overweight are urgently needed.
Glucagon-like peptide 1 (GLP-1) is a gastrointestinal hormone, secreted from the L-cells in the distal ileum and colon in response to the ingested nutrients. GLP-1 regulates appetite and food intake via gut-brain communications and stimulates insulin secretion from pancreatic β-cells. Even though GLP-1 is an effective appetite regulator, its half-life is less than 2 min due to rapid degradation by enzyme, and only 10–15% of endogenously secreted GLP-1 reaches the systemic circulation. In humans, GLP-1 secreting L-cells are highly localized in the distal part of the intestine, while digested food components are mainly absorbed in the small intestine. These difficulties hinder the use of nutritional compounds for appetite regulation via stimulating endogenous GLP-1 release. Hence, a novel system for delivery of nutritional compounds to the distal part of the intestine might increase and prolong GLP-1 secretion, and lead to a suppression of food intake.
α-linolenic acid (αLA) and porous silicon (PSi) particles were selected as a model nutrient and carrier, respectively. αLA is an essential long-chain fatty acid, highly abundant in seed and vegetable oils. PSi particles have been used in drug delivery systems due to their advantages as a carrier material, such as biodegradable, non-toxic, and non-immune-reactive. Freshly prepared PSi particles need surface modification to stabilize and optimize the particles. The aims of this thesis were to evaluate the biodegradation properties of different surface types of PSi particles, to determine the ability of αLA loaded PSi particles to stimulate GLP-1 secretion, and to examine the effects of orally administered αLA loaded PSi particles on the plasma GLP-1 level and food intake of mice.
The surface chemistry of PSi particles significantly affected their in vitro dissolution and in vivo biodegradation rate. For loading αLA, thermally hydrocarbonized PSi (THCPSi) particles were selected. αLA was released from THCPSi particles by diffusion, and αLA loaded PSi particles significantly increased GLP-1 secretion from enteroendocrine cells. Moreover, orally given αLA loaded PSi particles stimulated and prolonged the plasma GLP-1 concentration and inhibited the food intake of mice. In conclusion, nutrient-loaded PSi particles could serve as a novel treatment approach for obesity and overweight, by stimulating the endogenous release of gastrointestinal hormones.
Last updated: 22.4.2022