Metabolic effects of the gastrointestinal hormone secretin with focus on brown adipose tissue
Year: 2021
Type: dissertation
Abstract: In recent years, brown adipose tissue (BAT) has been of interest in metabolic research, because its activity is associated with reduced cardiovascular risk, insulin resistance and obesity. Since cardiovascular disease accounts for the greatest cause of death globally, new treatments and methods of prevention are needed. BAT can burn fat instead of storing it, but it is likely that energy dissipation alone does not explain its health benefits. Meal induced BAT thermogenesis has recently been shown in humans, but its regulators and significance have never been pursued in detail. Since some gastric hormones have already shown both cardioprotective and appetite suppressing effects, they provide an interesting target for further studies. Secretin is the oldest known hormone and belongs to a family of gastrointestinal peptides, secreted during feeding. The aim of this thesis was to study the metabolic effects of secretin beyond its well-known pancreatic exocrine stimulation. Mouse models were first implemented by collaborators at the Technical University of Munich to investigate the potential of using secretin to activate BAT thermogenesis and induce satiation. A placebo-controlled crossover study was then conducted at the Turku PET Centre with healthy male volunteers to study BAT activation, but also the broader pleiotropic effects of secretin. Tissue metabolic activity was quantified with positron emission tomography, using a fluoride labelled glucose tracer. Appetite was studied with functional magnetic resonance imaging. Mouse models showed that secretin directly activates BAT thermogenesis through binding to the secretin receptor and that BAT thermogenesis in turn suppresses appetite. This novel satiation stimulating gut – BAT – brain axis was then shown in this thesis work to also translate to humans. Furthermore, myocardial glucose uptake was increased by secretin in humans. Previous studies have shown increased cardiac output by secretin and this thesis supports an inotropic effect. All in all, these results indicate that further clinical trials on secretin are warranted, as it could have potential applications in weight control and both preventing and treating heart disease.
Source: UTUPub (University of Turku)
Author: Laurila, Sanna
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7011281059