title: Phospholipid homeostasis and lipotoxic cardiomyopathy: a matter of balance.
abstract: 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.
authors.affiliation: Development and Aging Program, Neuroscience, Aging and Stem Cell Research Center, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA.
authors.forename: Hui-Ying
authors.initials: HY
authors.lastname: Lim
authors.forename: Rolf
authors.initials: R
authors.lastname: Bodmer
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000209:etiology*; D004330:Drosophila; D006706:Homeostasis; D050155:Lipogenesis; D009765:Obesity / Q000150:complications*; D010641:Phenotype; D010743:Phospholipids / Q000378:metabolism*; D051779:Sterol Regulatory Element Binding Proteins / Q000378:metabolism*
chemical_list: D010743:Phospholipids; D051779:Sterol Regulatory Element Binding Proteins