Adiponectin : key role and potential target to reverse energy wasting in chronic heart failure
Faculty of Medicine and Health Sciences
Heart failure reviews
, p. 557-566
University of Antwerp
The concept of skeletal muscle myopathy as a main determinant of exercise intolerance in chronic heart failure (HF) is gaining acceptance. Symptoms that typify HF patients, including shortness of breath and fatigue, are often directly related to the abnormalities of the skeletal muscle in HF. Besides muscular wasting, alterations in skeletal muscle energy metabolism, including insulin resistance, have been implicated in HF. Adiponectin, an adipocytokine with insulin-sensitizing properties, receives increasing interest in HF. Circulating adiponectin levels are elevated in HF patients, but high levels are paradoxically associated with poor outcome. Previous analysis of m. vastus lateralis biopsies in HF patients highlighted a striking functional adiponectin resistance. Together with increased circulating adiponectin levels, adiponectin expression within the skeletal muscle is elevated in HF patients, whereas the expression of the main adiponectin receptor and genes involved in the downstream pathway of lipid and glucose metabolism is downregulated. In addition, the adiponectin-related metabolic disturbances strongly correlate with aerobic capacity (VO2 peak), sub-maximal exercise performance and muscle strength. These observations strengthen our hypothesis that adiponectin and its receptors play a key role in the development and progression of the "heart failure myopathy". The question whether adiponectin exerts beneficial rather than detrimental effects in HF is still left unanswered. This current research overview will elucidate the emerging role of adiponectin in HF and suggests potential therapeutic targets to tackle energy wasting in these patients.