Muscle and fat tissue wasting in patients with chronic heart failure: the impact of impaired insulin sensitivity

• Applicant: Professor Dr. Wolfram Döhner, Ph.D.
• Subject Area: Anatomy and Physiology
• Term: from 2007 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 34181657

Chronic heart failure (CHF) leads to skeletal muscle atrophy in the form of cardiac cachexia; the condition is lethal. Iron plays a key role in oxygen uptake, transportation and storage, as well as oxidative metabolism in skeletal muscle. Latent and overt iron deficiency has been observed as important characteristic of CHF leading to anemia of chronic illness as a common feature in CHF patients. We found that iron metabolism might exert an influence on this condition. We observed that iron repletion in CHF patients with iron deficiency improved symptomatic status and muscle functional capacity in patients with CHF. Importantly, we observed this effect even in patients that had CHF, but were not anemic. These patients had serum ferritin levels <100 μg or was between 100 and 299 μg per liter when the transferrin saturation was less than 20%. How iron might improve muscle performance in these patients, independent of hemoglobin levels is unknown. We hypothesize that hepcidin signaling might be involved. In this phase of CRG192, we will investigate pathways and regulation of iron balance in CHF on systemic, interstitial and at tissue levels both in skeletal muscle and the heart. Furthermore, the effect of iron supplementation on muscle metabolic and functional status will be studied.

• DFG Programme: Clinical Research Units
• Subproject of: KFO 192: Skeletal Muscle Growth Regulation and Dysregulation
• Participating Person: Professor Dr. Stefan Anker