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Does stress make us fat?
Stress hormones promote diabetes and obesity later in life

Ulm University

The fact that stress can cause inflammatory responses in the body and make us sick is old news. Scientists at Ulm University and the University of Vienna have now found out why stress hormones like cortisol have such a tremendous influence on our fat metabolism. They came across a molecular mechanism that can explain the development of obesity and diabetes in older age.

'We blocked the transmission of specific stress signals in fat cells and analysed how this affects glucose metabolism as well as fat build-up and fat reduction,' explains Professor Jan Tuckermann, Director of the Institute of Comparative Molecular Endocrinology at Ulm University. The main focus was put on the effects of cortisol. The stress hormone, which is biochemically classified as glucocorticoid, is not only a key player in the suppression of inflammatory responses, but also controls the mobilisation of energy in stressful and dangerous situations.

This hormone acts on a glucocorticoid receptor (GR) located in the cytoplasm of the cell. When activated, the receptor permeates the cell nucleus and regulates its genetic activity. 'We genetically deactivated this receptor molecule in the fat cells of mice and thus blocked the cortisol-induced stress signal in order to determine how important the effect of cortisol is for metabolism,' Dr. Kerstin Hartmann elaborates. The research assistant from the Tuckerman lab in Ulm, who now works for the company BioNTech Diagnostics, is one of two lead authors of the study, which was published in the journal 'Diabetes'. The other lead author is Dr. Kristina Müller from the Ludwig Boltzmann Institute for Cancer Research in Vienna.

The researchers at Vienna-based Boltzmann Institute looked at how the blockage of the stress hormone receptor affects the metabolism of mice when they are put on a reduction diet. 'Due to the blocked stress response the fasting mice cannot utilise the energy reserves from their fat cells. To compensate the body relies on other energy sources, which fundamentally interferes with the entire metabolism,' says Professor Richard Moriggl, Director of the Ludwig Boltzmann Institute for Cancer Research. He and Jan Tuckermann co-led the research project.

What happens when mice with a blocked GR receptor are put on a high-fat diet, or when they simply age? That's what the scientists in Ulm investigated. Similar to humans, as mice get older their body fat usually increases. 'In this study, the mice with blocked stress signals were much slimmer than the respective wild-type animals in the control group. This was true for both the old ones as well as the ones on a high-fat diet,' Tuckermann reports. They not only had smaller fat depots, but also markedly less fat deposits in the liver than those mice whose cortisol signalling pathways in the fat cells were unimpeded. Furthermore, the glucose metabolism of the genetically modified mice was improved considerably. The result: a significantly reduced risk of diabetes. 'These results imply that stress hormones may speed up weight gain and promote adult-onset diabetes,' the researchers from Ulm and Vienna conclude, who had support from scientists from the Helmholtz Diabetes Center in Munich and the biotech company Joanneum Research. The study was funded by the German Research Foundation (DFG) and the EU.

Now, what is the medical relevance of all this? Age-associated diseases like obesity come with a wide range of serious comorbidities. This includes cardiovascular diseases like cardiac infarction and stroke, but also metabolic diseases like diabetes. 'If we can determine the role played by stress hormones like cortisol, which mediate between inflammatory and metabolic processes, we might be able to identify new ways to positively influence pathologically changed metabolic processes via the involved signalling pathways,' Tuckermann believes.

Text and media contact: Andrea Weber-Tuckermann

Project team member Dr. Sabine Vettorazzi analyses liver slices. As metabolic organ the liver is involved in fat metabolism. (photo: Elvira Eberhardt / Ulm University)
Project team member Dr. Sabine Vettorazzi analyses liver slices. As metabolic organ the liver is involved in fat metabolism. (photo: Elvira Eberhardt / Ulm University)
Foto: Elvira Eberhardt / kiz
Prof. Jan Tuckermann (photo: Elvira Eberhardt / Ulm University)
The fat cells of the wild-type mice in the control group (left) are considerably bigger after a high-fat diet than those of the mice with deactivated GR receptors (right), in which the cortisol-induced stress signal is blocked.
The fat cells of the wild-type mice in the control group (left) are considerably bigger after a high-fat diet than those of the mice with deactivated GR receptors (right), in which the cortisol-induced stress signal is blocked. (microscopic image: Dr. Kerstin Hartmann)
Reconstruction based on micro computer tomography imaging. The figure shows very similar effects: The mice with blocked cortisol-based stress signals have a lower percentage of subcutaneous fat (pink), which is well visible to the naked eye, but also meas
Reconstruction based on micro computer tomography imaging. The figure shows very similar effects: The mice with blocked cortisol-based stress signals have a lower percentage of subcutaneous fat (pink), which is well visible to the naked eye, but also measurably less visceral fat (grey). (figure: Dr. Kerstin Hartmann)