PhD defence: The liver-derived hormones GDF15 and FGF21 and their effect on energy balance

Trine Sand Nicolaisen

PhD thesis

Growth differentiation factor 15 (GDF15) and fibroblast growth factor 21 (FGF21) are hormones that are primarily secreted by the liver. While the pharmacological effects of these hormones and their significant impact on energy metabolism have been extensively investigated in mice, their physiological roles remain incompletely understood in both mice and humans.

To address this, the physiological effects of endogenous plasma GDF15 levels on appetite following a single bout of exercise or metformin administration in both humans and mice was investigated. Additionally, the impact of increased endogenous plasma FGF21 levels, induced by a prolonged eucaloric protein-restricted diet, on energy utilization was investigated in lean male volunteers.

Our findings revealed that the endogenous GDF15 levels increased following exercise and metformin administration but was dispensable for the changes in appetite seen with both interventions. Additionally, we observed that a protein-restricted diet led to increased endogenous FGF21 levels and enhanced energy utilization, suggesting that a protein-restricted diet has the potential to prevent weight gain and the development of obesity.

Download Table of contents; Abstract; Resumé (Danish), List of manuscripts; Publication list.

2023, 120 pages.

Time

3 July 2023, 13:00

Place

Aud. 1, August Krogh Building, Universitetsparken 13, DK-2100 Copenhagen.

Opponents

Associate Professor Anke Ninija Karabanov (chair), Department of Nutrition, Exercise and Sports, University of Copenhagen, Denmark.

Professor Ellen Blaak, Department of Human Biology, Faculty of Health, Medicine and Life Sciences, University of Maastricht, Netherlands.

Principal Scientist Matthew Paul Gillum,, Novo Nordisk A/S, Denmark.

Main supervisor

Professor Bente Kiens, Department of Nutrition, Exercise and Sports, University of Copenhagen, Denmark.

Co-supervisor

Associate Professor Christoffer Clemmensen, Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.

(former) Assistant Professor Anders Bue Klein, Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.

The thesis is available for inspection at Nørre Allé 51, DK-2200 Copenhagen N.