(Vienna, 3 October 2016) A team of researchers led by Richard Moriggl from the Ludwig Boltzmann Institute for Cancer Research (LBI-CR), VetMedUni Vienna and the Medical University of Vienna, with international participation from universities in Ulm and Munich, has investigated the effect of a diminished stress hormone signal on fat cells. The main observation in the animal model was that a diminished stress signal in fat cells results in leaner old mice and protects against adult-onset diabetes.
More than 600,000 people in Austria suffer from diabetes and an even greater number are very overweight, which can trigger or accelerate many diseases. Prophylactic drugs to prevent typical diseases are therefore an important health topic.
Glucocorticoids are hormones that act on every cell in the body. The best known amongst them is cortisone, which has been successfully used for many years as a medication to suppress inflammation, autoimmune diseases and chronic allergies. Glucocorticoids also play an important role in metabolism and are equally regarded as stress hormones. They are important for mobilising energy, which is crucial in dangerous situations, such as in the face of infections or during long periods of food shortage. The hormones coordinate the complex interaction between the brain, glands, fat deposits, liver and even the muscle tissue. Hormones can bring about great changes in the metabolic process. For example, the typical age-related weight gain with associated fatty liver or diabetes can be partially due to changes in hormone levels. These health problems are expedited by complex interactions between different organs and hormones and the aim of the study was to gain a better understanding of these interactions. In this way it would then be possible to influence stress hormones with drugs, in order to treat obesity and diabetes.
A research team led by Richard Moriggl from the Ludwig Boltzmann Institute for Cancer Research (LBI-CR), the University of Veterinary Medicine Vienna and the Medical University of Vienna, with international participation from universities in Ulm and Munich, has now investigated the effect of a diminished stress hormone signal on fat cells. The main observation was that a diminished stress signal in fat cells results in leaner old mice and protects against adult-onset diabetes. Hormonal action is conveyed via receptors that sit close to the cell surface and produce signals inside the cell when a stress hormone is released. In order to disrupt transmission of these signals, the researchers studied mice whose fat cells were incapable of generating a stress hormone response. The research group has now published its findings in the renowned journal "Diabetes”.
The absence of any stress hormone response leads to the loss of energy reserves from fat cells and, following a period of starvation, these fat cells were huge, as the fat could not be mobilised. To balance this out, the body turned to other endogenous energy sources and so the loss of the receptor in the fat cells results in fundamental disruption of the entire metabolic process. A surprising consequence was that, after receiving a particularly high-fat diet, the mice were less overweight than comparison animals. Even when they were old, the mice with no stress hormone response had a significantly lower body weight. "We were surprised by the fact that, in the long term, reduced fat breakdown results in less fatty tissue in the body," explains Moriggl. It is therefore not the absence of stress but rather too much stress that makes mice, or at least old mice and mice fed on unhealthy diets, overweight. We believe that the stress hormone balance is more fragile in later life and is more prone to accelerating typical age-related phenomena, such as obesity and diabetes, in humans. An interesting aspect of the study was that genetically modified mice without a stress hormone response had better blood glucose levels. It remains to be seen whether this can be exploited in the treatment of diabetes.
Adipocyte Glucocorticoid Receptor Deficiency Attenuates Aging- and Hfd-Induced Obesity, and Impairs the Feeding-Fasting Transition.
Mueller KM, Hartmann K, Kaltenecker D, Vettorazzi S, Bauer M, Mauser L, Amann S, Jall S, Fischer K, Esterbauer H, Müller TD, Tschöp MH, Magnes C, Haybaeck J, Scherer T, Bordag N, Tuckermann JP, Moriggl R.
Diabetes. 2016 Sep 20. pii: db160381. DOI: 10.2337/db16-0381