For the next 3 years, Malene Revsbech Christiansen will be on the lookout for the biological factors responsible for weight gain, so as to enable better selection of the genes suitable for treating obesity and type 2 diabetes. She will be doing this for her PhD project at the Metabolism Center at the University of Copenhagen, for which she has just been granted DKK 1.1 million by the Danish Diabetes Academy.

‘Obesity and type 2 diabetes are a massive burden on society and very costly for the health sector. Today, nearly 2 billion people are overweight, and that number is expected to grow in coming decades. We therefore need to combat and prevent obesity in order to avoid further growth in mortality from obesity complications such as type 2 diabetes’, she says.

Malene Revsbech Christiansen’s research interest is leptin, an appetite- and energy-regulating hormone that is produced and secreted by adipose tissue and sends signals to the brain about the body’s energy depots.

She is now setting out to identify and characterize novel genetic variants that regulate leptin levels during weight loss and to examine their role in weight loss maintenance, insulin resistance and the risk of type 2 diabetes.

What researchers know is that severe obesity caused by leptin deficiency can be treated with leptin, which also reduces metabolic complications. However, they do not know how leptin affects metabolic health in the population at large. The latest research has shown that leptin may be regulated by genes that are expressed specifically during weight loss and may help with maintaining the weight loss.

To identify new genetic variants, the group will use data from six international weight loss interventions that measured leptin levels before and after weight loss. In follow-up analyses, they will examine the association between the variants identified and any weight gain following the weight loss. They will also use data from five Danish cohort studies to look into the association between a 5-year weight gain and changes in insulin resistance and other metabolic diseases in the population at large.

‘This way, we can study the association between the genetic variants and the risk of type 2 diabetes and cardiovascular disease, and by using published genome-wide association studies and over half a million individuals from UK Biobank we can investigate whether the genetic variants also affect other complex human diseases’, says Malene Revsbech Christiansen.

The final part of her project will be to study the effect of causal genes in leptin-associated regions on leptin expression, production and secretion by human fat cells stimulated by insulin and steroid hormone.

‘The results of this project will give us a better understanding of the role of leptin during weight loss, and we will also learn about how the genetic variants affect a stable weight and about the risk of metabolic disease in obese people and the general population’, she says.

CONTACT
Malene Revsbech Christiansen
Novo Nordisk Foundation Center for Basic Metabolic Research, and Faculty of Health and Medical Sciences, University of Copenhagen
malene.christiansen@sund.ku.dk
+45 35 32 22 49

‘Obesity and type 2 diabetes are a massive burden on society and very costly for the health sector. Today, nearly 2 billion people are overweight, and that number is expected to grow in coming decades. We therefore need to combat and prevent obesity in order to avoid further growth in mortality from obesity complications such as type 2 diabetes.’