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Obesity, which increases the risk of developing type 2 diabetes, has grown into a global challenge, and more knowledge of how to prevent and treat it is urgently needed. To that end, in her PhD project, Stephanie Holm intends to reveal the part played by a special type of fatty acid – known as medium-chain fatty acids – in controlling our appetite.

You have probably heard of saturated and unsaturated fat, but what are medium-chain fatty acids? Fatty acids consist of chains of carbon atoms, and medium-chain fatty acids are saturated fatty acids six, eight, ten or twelve carbon atoms long. Medium-chain fatty acids are found, for example, in dairy products and coconut oil.

‘It has been shown that foodstuffs containing large quantities of medium-chain fatty acids (MCFAs) reduce calorie intake both in rodents and in humans. However, the signalling mechanisms behind the properties of high MCFA intake have not yet been elucidated. Large quantities of MCFA are absorbed directly by the liver from the portal vein, so an obvious thing to investigate is whether the appetite-regulating effect of MCFA is mediated via the liver’, explains Stephanie Holm, who recently completed her master’s in human biology at the University of Copenhagen.

It is the liver that produces a hormone called liver-expressed antimicrobial peptide 2 (LEAP2). We already know that LEAP2 can suppress appetite by blocking a so-called ghrelin receptor. Stephanie Holm intends to examine whether it may be medium-chain fatty acids from food that increase LEAP2 production via the liver and thereby suppress the appetite.

‘This is an important step in identifying the significance of LEAP2 and the liver in relation to body weight regulation, and it may point the way to new methods of obesity treatment’, says Stephanie Holm.

Three mouse-to-human studies, three collaborative partners and a trip to Australia

Stephanie Holm will carry out three studies in her PhD project. In the first study, she will find out whether medium-chain fatty acids raise the level of LEAP2 in liver cells taken from both mice and humans. To see whether findings in mice can be transferred to humans, she will also conduct a clinical study in which she will measure whether medium-chain fatty acid intake increases the volume of LEAP2 in the blood. The clinical study will be carried out in collaboration with Professor Sten Madsbad at Hvidovre Hospital.

The second study will investigate whether medium-change fatty acids’ appetite suppression takes place via LEAP2. Stephanie Holm will investigate this using mice that lack either LEAP2 or the ghrelin receptor. This study will be conducted in collaboration with Dr Zane B. Andrews at the Monash Biomedicine Discovery Institute in Australia, where Stephanie Holm plans a six-month research visit.

In the final study, Stephanie will get right down to detail and examine which cell mechanisms control LEAP2 production. This third study will take place in collaboration with Siv Annegrethe Hjort of the Center for Basic Metabolic Research at the University of Copenhagen.

The principal supervisor on the project is Birgitte Holst MD, PhD, a researcher recognized as an international leader in the field.

By Nina Jensen, Project Manager, Danish Diabetes Academy

Facts

Name and title: Stephanie Holm MSc, b. 1994

Awarded DKK 1.1 million by the Danish Diabetes Academy.

Project title: The Impact of Medium Chain Fatty Acids in the Regulation of the Appetite Modulating Hormone, Liver Expressed Antimicrobial Peptide 2 (LEAP2)

Research centre: Department of Biomedical Sciences, University of Copenhagen
Principal supervisor: Birgitte Holst MD, PhD

Email: stephanie.holm@sund.ku.dk

Tel: +45 27 82 46 41

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Contact Danish Diabetes Academy

Tore Christiansen, Managing Director

Email: tore.christiansen@rsyd.dk

Tel: +45 2964 6764