title: Lipid metabolism and signaling in cardiac lipotoxicity.
abstract: The heart balances uptake, metabolism and oxidation of fatty acids (FAs) to maintain ATP production, membrane biosynthesis and lipid signaling. Under conditions where FA uptake outpaces FA oxidation and FA sequestration as triacylglycerols in lipid droplets, toxic FA metabolites such as ceramides, diacylglycerols, long-chain acyl-CoAs, and acylcarnitines can accumulate in cardiomyocytes and cause cardiomyopathy. Moreover, studies using mutant mice have shown that dysregulation of enzymes involved in triacylglycerol, phospholipid, and sphingolipid metabolism in the heart can lead to the excess deposition of toxic lipid species that adversely affect cardiomyocyte function. This review summarizes our current understanding of lipid uptake, metabolism and signaling pathways that have been implicated in the development of lipotoxic cardiomyopathy under conditions including obesity, diabetes, aging, and myocardial ischemia-reperfusion. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk.
authors.affiliation: Dalhousie Medicine New Brunswick, Department of Biochemistry and Molecular Biology, Dalhousie University, 100 Tucker Park Road, Saint John, New Brunswick, Canada.
authors.forename: Kenneth
authors.initials: K
authors.lastname: D'Souza
authors.affiliation: Dalhousie Medicine New Brunswick, Department of Biochemistry and Molecular Biology, Dalhousie University, 100 Tucker Park Road, Saint John, New Brunswick, Canada.
authors.forename: Carine
authors.initials: C
authors.lastname: Nzirorera
authors.affiliation: Dalhousie Medicine New Brunswick, Department of Biochemistry and Molecular Biology, Dalhousie University, 100 Tucker Park Road, Saint John, New Brunswick, Canada. Electronic address: pkienesb@Dal.Ca.
authors.forename: Petra C
authors.initials: PC
authors.lastname: Kienesberger
mesh_terms: D000818:Animals; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects*; D008055:Lipids / Q000633:toxicity*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D008055:Lipids
keywords: Cardiomyopathy; Diabetes; Heart; Lipids; Lipotoxicity; Obesity