Clinical Translational Metabolism Group

Currently, the Clinical Translational Metabolism group is working within different research areas related to clinical obesity research:

The RESETTLE Study

At least 25% of adolescents with childhood-onset obesity are untreatable by lifestyle changes. This group of adolescents is very vulnerable as they have a high risk of developing morbid obesity, type 2 diabetes and cardiovascular disease already as young adults. Moreover, psychological consequences such as social isolation, anxiety, body-dissatisfaction and depression are commonly seen along with lower health-related quality-of life. Thus, there is an urgent need for early identification of risk factors and implementation of new treatment modalities in adolescents with childhood-onset obesity, who do not respond to structured lifestyle interventions.

Why they develop untreatable obesity is unknown and is not explained by socioeconomic factors or genetic variants. However, inappropriate eating behavior such as emotional and uncontrolled eating as well as increased reward responses to high-calorie food may be underlying factors behind childhood-onset obesity. Glucagon-like peptide-1 (GLP-1) is a hormone secreted from the gut upon food intake and promotes satiety. Due to the appetite inhibiting effects of GLP-1, agonists of the GLP-1 receptor (GLP-1 RAs) leads to weight loss of around 10 %, and the GLP-1 RA liraglutide is approved for long-term weight management as supplement to caloric restriction and increased physical activity in adults with a BMI above 30. Moreover, GLP-1 RA treatment may lower food cravings and reduce inappropriate eating behavior.

Thus, the primary objective is to evaluate the effect of supplementing caloric restriction and physical activity with appetite inhibition in form of the GLP-1 RA liraglutide in order to achieve weight loss in otherwise treatment resistant young adults with childhood-onset obesity.

We hypothesize that GLP-1 RA supplement, as add on to caloric restriction and physical activity can facilitate weight loss and improve appetite dysfunctions and eating behavior in young adults with treatment-resistant childhood-onset obesity.

We will test this by investigating the effect of applying GLP-1 RA treatment on top of life style changes in young adults with early-onset treatment resistant obesity

Our overall goal is to provide evidence for a new intervention regimen, allowing the health care sector to help vulnerable adolescents with childhood-onset obesity by early identification and focused evidence-based therapy to improve health and quality of life.

The S-LiTE study

"S-LiTE" is an abbreviation for "Synergy effect of the appetite hormone GLP-1 (LiragluTide) and Exercise in maintenance of weight loss and health after a low calorie diet. The randomized controlled trial started recruitment in August 2016 and is running for several years. See the project's facebook site

Obesity affects 1 billion people and impairs all aspects of health; therefore there is an acute need for better treatment strategies. Chronic inflammation is an established part of the pathogenesis of obesity. Glucagon-like-peptide-1 (GLP-1) reduces food intake. We have previously shown that: 1) obese people have low endogenous GLP-1 response; 2) weight loss induces a marked increase in GLP-1 response, and 3) treatment with GLP-1 analogues facilitates long term weight loss maintenance accompanied by substantial improvement in metabolic health, compared to diet-induced weight loss maintenance. Exercise seem to ensure a more healthy weight loss maintenance and immuno-metabolic profile compared to diet-induced weight loss alone, by influencing systemic and adipose tissue inflammatory pathways. Emerging evidence identify GLP-1 as a potentially important immuno-modulator. Thus, both exercise and GLP-1 analogue treatment seem to facilitate weight loss maintenance, improve metabolic health and reduce systemic inflammation. We therefore hypothesize that combined treatment with GLP-1 and exercise exerts positive synergistic effects on immuno-metabolic health. Following a diet-induced weight loss we will test the individual and combined effects of GLP-1 analogue and exercise treatment on  immuno-metabolic health biomarkers, remission of metabolic syndrome and weight loss maintenance; enrichment of the microbiota and amelioration of the epigenetic signature of spermatozoa.

Thus the goal is to establish novel and interdisciplinary strategies to improve immuno-metabolic health and maintain weight loss. By applying state-of-the-art methods, we wish to identify new pathways and generate targets for sustainable and immuno-metabolic health-promoting weight loss strategies.

Melanocortin-4 receptor mutations and GLP-1

Mutations in the melanocortin-4 receptor (MC4R) gene represent the most common monogenic cause of severe childhood obesity. The MC4R is expressed in the hypothalamus in the brain and is an important regulator of food intake, energy expenditure and glucose homeostasis. Glucagon-like peptide (GLP) -1 is an incretin hormone that potentiates glucose-stimulated insulin secretion and also acts as an appetite-inhibiting hormone affecting the appetite center in the hypothalamus.

The aim of this project is to explore if the MC4R is part of the appetite inhibiting effect of GLP-1 and to investigate the physiological role of GLP-1 concerning body weight and appetite regulation in MC4R mutation carriers. Our hypothesis is that GLP-1 acts independently of the MC4R in the hypothalamus, and analogues of GLP-1 thus may serve as a treatment option for these patients.

Glucose metabolism in patients with mutations in voltage-gated potassium channels (long QT patients)

Voltage gated-potassium channels are located in the heart but also in glucose-regulating organs such as the pancreas and the intestine.
Therefore, we investigate the glucose metabolism in patients with loss of function mutations in the Voltage-gated potassium channels (long QT syndrome patients).

Read article about the project

Member of the NNF TrlC consortium: Discovery and validation of novel targets for therapy, characterization and response to treatment in immuno-metabolic diseases

The programmes both combine the fields of immunology and metabolic research and bring together investigators from three institutions; University of Copenhagen, Denmark, University of Oxford, Great Britain, and the Karolinska Institute, Sweden

Instructors: Jens Juul Host and Signe Sørensen Torekov. 

This diabetes course will give you the newest state of the art updates on diabetes research in the fields of clinical aspects of diabetes and regulation of insulin secretion, epidemiology of diabetes, heritability of diabetes, genetic aspects of diabetes, prevention of diabetes and insulin resistance, molecular insulin resistance, cellular aspects of diabetes, physiological regulation of blood glucose, type 1 diabetes and stem cell research in diabetes. Each section will be covered by world leading professors (to be announced) in the specific areas. 

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In June 2017, Associate professor Signe Sørensen Torekov was awarded the Anders Jahre Prize for young researchers based on her research in obesity and diabetes.  

Anders Jahre's medical prizes reward excellent research in basic and clinical medicine. The prizes are awarded by the University in Oslo and are among the largest in medicine in the Nordic region.

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