Muscle wasting

To elucidate the role of cellular processes, with a special focus on autophagy pathway, in the development of skeletal muscle loss and organ failure in the critically ill patients. In addition, we also try to understand how nutrition can impact these mechanisms.

Project leader

Aim

To elucidate the role of cellular processes, with a special focus on autophagy pathway, in the development of skeletal muscle loss and organ failure in the critically ill patients. In addition, we also try to understand how nutrition can impact these mechanisms.

Description

We are using a translational approach where we combine material obtained from patients hospitalized in our mixed intensive care unit (ICU), i.e. serum, muscle cryosections, with an in vitro experimental model using human primary muscle cells and human primary liver cells. The use of this approach allows us to understand and study autophagy dynamics and regulation during critical illness. We are also measuring which molecule(s) or cocktail of molecules present in the serum of patients are involved in the regulation of autophagy, using metabolomic analysis.

Main results and publications

Withholding of early parenteral feeding during the first week in the ICU has become a common ICU nutritional routine. However, the mechanism or proof of the deleterious effect of early parenteral nutrition on autophagy and organ failure development are scarce and still largely unknown. In the first paper published from this new project, we have observed that a block of autophagy might be indeed present in some ICU patients, but that this block might be unrelated to nutrition. However, the starvation mimicked by the withholding of early parenteral nutrition might be beneficial via the effect of starvation on reactivation of the autophagy pathway.

Collaborators

Olav Rooyackers (KI),
Urban Flaring (KI),
Anna Strömberg (KI)

Funding

Swedish Research Council, Lars Bindslevs Minnesfond.