Crosslinked cellular power plants for a slim look

Neuherberg, 30.09.2015. Our body consistently adjusts its energy management to changes in the supply of nutrients or physical activity. Malfunctioning in this process plays an essential role in the genesis of metabolic disorders like adiposity and diabetes. Scientists at the Helmholtz Zentrum München now report in the journal Cell Metabolism that in this process the protein calcineurin assumes a central function by selectively linking up mitochondria in the muscle with each other and in that way optimising cell respiration.

Mitochondria transform absorbed dietary nutrients into energy. The "power plants" of the cells are joined together in a network that can be dynamically regulated by fusion or fission of mitochondria, depending on the activity and needs of the cell. Scientists at the Helmholtz Zentrum München report a new mechanism on how muscle cells utilize the formation of elongated mitochondrial nanotunnels to optimize cellular respiration and energy and glucose management throughout the entire body.

Calcineurin identified as a key molecule
Crucial in this context is the molecule calcineurin. "In our study, we could show that flies that cannot produce any calcineurin had less weight, less fat storage as well as an increased metabolic rate" says Dr Paul Pfluger from the Institute for Diabetes and Adiposity (IDO), who headed the international team of scientists from the German Centre for Diabetes Research (DZD) and the United States.

And apparently the flies are no evolutionary peculiarity: mice with a calcineurin defect were also, despite high-fat diet, protected against excessive weight and showed enhanced expenditure of calories. In order to confirm this effect, the scientists specifically inhibited the effect of calcineurin by means of an inhibitor called tacrolimus*. In actual fact, this treatment was also able to reduce weight gain from high-calorie nutrition.

Calcineurin inhibitors in the clinic for years
"A mechanism so well preserved evolutionarily for control of metabolism in flies and mice suggests that calcineurin also performs a similar function in humans," Paul Pfluger speculates. "It would therefore be an obvious conclusion to suppress the function of calcineurin through medication in order to treat obesity." Corresponding inhibitors have been deployed in high dosages in the clinic for years in order to prevent rejection reactions after tissue transplants but due to numerous side effects have not been above criticism. Effects from low-dosage calcineurin inhibitors on the body weight of adipose patients have, however, not yet been studied clinically. "In our opinion, such a study with low concentrations of calcineurin inhibitors is quite apropos. Corresponding new approaches are currently being tested," according to Pfluger.

* Tacrolimus has for years been administered in high doses to suppress the immune system. The molecule is used with rejection reactions or atopic eczema cases. Systematic administration is however associated with numerous side effects.

Original publication:
Pfluger, P. et al. (2015). Calcineurin Links Mitochondrial Elongation with Energy Metabolism, Cell Metabolism, DOI: 10.1016/j.cmet.2015.08.022

Link to the publication: