In Search of Mechanisms that Make Weight Loss Difficult | Danish Diabetes and Endocrine Academy
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In Search of Mechanisms that Make Weight Loss Difficult

Virtually all of us who have struggled to lose weight know that one quickly gains at least as much again. The probable explanation is that the body does not want to lose weight and responds by reducing resting metabolism, whereby less fat is burned. Now new research is setting out to investigate possible new mechanisms for regulating resting metabolism in relation to obesity and weight loss.

“If we can succeed in acquiring this knowledge, it may be beneficial for the development of new drugs that can limit the rapidly increasing obesity epidemic,” says Jens Frey Halling. Thanks to a grant of DKK 600,000 from the Danish Diabetes Academy and with co-financing from Novo Nordisk, he was recently able to embark on his study in a postdoc project.

Jens Frey Halling, MSc, PhD, works at University of Copenhagen, Department of Biology.

He says there is a lack of knowledge about the regulation of human resting metabolism. But the estimate is that about 30% of resting metabolism is spent on producing heat in the mitochondria of body tissue. The production of heat in the mitochondria involves membrane proteins decoupling the combustion of nutrients from the production of energy in the form of ATP. However, we still do not know how the mitochondria vary in the production of heat and energy consumption due to different availability of nutrients. Nor do we know how important the mitochondria are when it comes to resting metabolism after weight loss.

Accordingly, Jens Frey Halling will investigate how resting metabolism can be regulated by so-called post-translational changes in the proteins of the mitochondria. “We will investigate this in muscle biopsies from subjects with both normal weight and excess weight, with and without a diagnosis of type 2 diabetes. We will also investigate the role of the mitochondria in regulating resting metabolism in mini pigs, which show a significant reduction in resting metabolism when their food intake is limited,” says Jens Frey Halling.

In his postdoc work he will collaborate with researchers at University of Southern Denmark, including Professor Martin Røssel Larsen. He will also visit Ottawa University in Canada for a few months to collaborate with Professor Mary-Ellen Harper on the analyses. He is no stranger to opportunities and working methods in Ottawa: he also completed part of his previous postdoc studies there.

Facts about the project

  • Newly-approved drugs can reduce appetite, thereby leading to moderate weight loss of up to 10% of body weight. But then the body lowers the resting metabolism. This probably helps explain why weight loss is usually very difficult to maintain in the long run.
  • The overall objective of the project is to investigate potential new mechanisms for regulating resting metabolism vis-à-vis obesity and weight loss. This knowledge may benefit the development of new drugs to limit the rapidly increasing obesity epidemic.
  • Obesity is the fifth largest risk factor in worldwide mortality, and obesity is closely linked to a number of other diseases such as cardiovascular disease, cancer and diabetes.



  • Jens Frey Halling, MSc, PhD

  • Awarded DKK 600,000 kr. by the Danish Diabetes Academy

  • Project title: Regulation of mitochondrial energy expenditure in obesity

  • Research institution: Department of Biology, University of Copenhagen, and Novo Nordisk A/S

  • Principal investigator: Professor Henriette Pilegaard, Department of Biology, University of Copenhagen

Jens Frey Halling
Tel: +45 22 83 18 96

Danish Diabetes Academy
Managing Director Tore Christiansen
Tel: +45 29 64 67 64