How do hormones from the gastrointestinal tract lead to lowered appetite and increased weight loss? A new postdoc project will investigate
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Can the effect of obesity surgery be achieved by drug treatment alone? And what actually happens in the brain when a combination of appetite-suppressing hormones is administered? Hannah Louise Zakariassen will investigate in a new postdoctoral project supported by the Danish Diabetes Academy.
The incidence of obesity and complications such as type 2 diabetes is rising steeply worldwide. At the same time, there are few treatment options. Today, surgery is the most effective treatment for obesity.
‘Unfortunately, surgery is associated with serious side effects, which means that there is still a need for effective pharmacological obesity treatment options that don’t cause unacceptable side effects at the same time’, says Hannah Louise Zakariassen, who holds a master’s degree in veterinary medicine and obtained her PhD from the University of Copenhagen in 2019.
Intestinal hormone plays a beneficial role
However, some of the mechanisms leading to weight loss from surgery may possibly be achievable through drug treatment. Intensive research is therefore being carried out to understand exactly how obesity operations lead to weight loss. The operations work partly by increasing the release of appetite-suppressing hormones from the gastrointestinal tract.
‘We have recently shown that the intestinal hormone neurotensin (NT) is important to appetite regulation and plays a part in the beneficial effects achieved by obesity surgery’, says Hannah Louise Zakariassen.
However, the effect of individual hormones such as neurotensin cannot explain the full effect of obesity operations, as numerous hormones are released. Hannah Louise Zakariassen will therefore investigate the synergy effect that occurs when the gastrointestinal hormones neurotensin and GLP-1 are administered at the same time.
Initial studies have shown that the hormones activate special regions in the brain that are involved in controlling the body’s energy balance. Hannah Louise Zakariassen therefore wants to look more closely at what happens in the brain. She hopes to come up with new knowledge that can be used to develop new forms of anti-obesity medication.
Elucidating the underlying mechanisms behind the appetite-suppressing and weight-lowering effect of combination treatment with NT and GLP-1 may lead to the identification of new targets for anti-obesity drugs. This may assist the development of new medications to treat metabolic diseases associated with obesity, such as type 2 diabetes’, says Hannah Louise Zakariassen.
Industrial collaboration and research visit to the USA
In collaboration with Gubra A/S, Hannah Louise Zakariassen will use advanced microscopy to take 3D images of mouse brains in order to compare post-treatment brain area activation with either one or both of the gastrointestinal hormones.
In addition, she is planning a three-month visit to Michigan State University in the USA, where, in collaboration with researcher Gina Leinninger, she will use mouse models to dig deeper into the molecular mechanisms behind the effect of the gastrointestinal hormones on the brain.
Thue Schwartz of the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen will also take part in the project, to which she will bring her expertise in the use of mouse models to study the role of the vagus nerve.
Internationally recognized researcher Birgitte Holst of the Department of Biomedical Sciences, University of Copenhagen, is PI on the project.
By Nina Jensen, Project Manager, Danish Diabetes Academy
Name and title: Hannah Louise Zakariassen PhD, b. 1986
Awarded DKK 1.8 million by the Danish Diabetes Academy.
Project title: Mechanisms underlying appetite suppressing and weight lowering effects of combination treatment with neurotensin and GLP-1 agonists in mice
Research centre: Department of Biomedical Sciences, University of Copenhagen
PI: Birgitte Holst, MD PhD
Tel: +45 2396 7960
Danish Diabetes Academy
Tore Christiansen, Managing Director
Tel: +45 2964 6764