Lipotoxicity in cardiac and skeletal muscle

Lipotoxicity is defined as the untoward consequences of the accumulation of excess lipid in non-adipose tissue. Fatty acids are an important substrate for myocyte metabolism, yet mismatch of cellular uptake and utilization results in lipid accumulation that is clearly detrimental. Within the myocyte, lipotoxicity can lead to cellular dysfunction, resulting in defective contraction or relaxation or both, alterations in key signaling pathways, and apoptotic cell death. In this review we discuss the significance of myocyte lipotoxicity in human disease and present insights into the pathophysiology gained from transgenic animal models of toxic lipid overload in skeletal and cardiac muscle. Heart Metab. 2006;30:00–00.