Functional adiponectin resistance and exercise intolerance in heart failure

The contribution of skeletal muscle myopathy to the phenotype of patients with chronic heart failure (CHF) has become generally accepted. Besides the macro- and microscopic changes that develop during the progressive process of muscular wasting, functional abnormalities manifest in an earlier stage. Analogous to the failing heart, alterations in skeletal muscle energy metabolism, including insulin resistance, are increasingly recognized. In the search for factors causing this observed myopathy, adipokines receive growing attention. In particular, adiponectin is of special interest due to its fundamental role in skeletal muscle energy metabolism. In strong contrast with patients at risk for cardiovascular disease, circulating adiponectin levels are increased in patients with CHF, and this finding is associated with adverse outcome. Recently, the concept of functional skeletal muscle adiponectin resistance has been suggested to explain compensatory elevated adiponectin levels in CHF. Unraveling of adiponectin's complex downstream signalling pathways and insights into the concept of adiponectin resistance hopefully will disengage the road for targeted therapeutic interventions.