Obesity has reached pandemic proportions globally and is often associated with lipotoxic
heart diseases. In the obese state, caloric surplus is accommodated in the adipocytes as
triglycerides. As the storage capacity of adipocytes is exceeded or malfunctioning,
lipids begin to infiltrate and accumulate in non-adipose tissues, including the myocardium of the heart, leading to organ dysfunction. While the disruption of caloric homeostasis has been widely viewed as a principal mechanism in contributing to peripheral tissue steatosis and lipotoxicity, our recent studies in Drosophila have led to the novel finding that deregulation of
phospholipid homeostasis may also significantly contribute to the pathogenesis of lipotoxic
cardiomyopathy. Fly mutants that bear perturbations in
phosphatidylethanolamine (PE) biosynthesis, such as the easily-shocked (eas) mutants defective in
ethanolamine kinase, incurred aberrant activation of the
sterol regulatory element binding protein (SREBP) pathway, thereby causing chronic lipogenesis and cardiac steatosis that culminates in the development of lipotoxic
cardiomyopathy. Here, we describe the potential relationship between SREBP and other eas-associated phenotypes, such as neuronal excitability defects. We will further discuss the additional implications presented by our work toward the effects of altered lipid metabolism on cellular growth and/or proliferation in response to defective
phospholipid homeostasis.