Stearic acid-induced cardiac lipotoxicity is independent of cellular lipid and is mitigated by the fatty acids oleic and capric acid but not by the PPAR agonist troglitazone.
The objective of this study was to examine the potential of stearic acid to induce cardiomyocyte cell death and the hypothesis that the amount of cellular lipid is a determinant of cell death. In cardiomyocytes from embryonic chick heart, stearic acid (SA) produced a significant (P < 0.001) concentration-dependent increase in cell death with an ED(50) of 71 microM. In contrast, capric (C10:0) or oleic acid (OA; C18:1), at < 200 microM, did not alter cell viability. Stearic acid-induced cell death was significantly reduced by OA and to a lesser extent by capric acid. Neither OA nor capric acid altered cell death produced by potassium cyanide and deoxyglucose. Stearic acid (100 microM) induced a significant (P < 0.05) twofold increase in cellular lipid as assessed by Nile blue and Sudan Black staining. A role for cellular lipid in cardiomyocyte death was excluded because OA increased cellular lipid, at concentrations that did not induce cell death; OA did not alter SA-induced cellular fat stores but reduced cell death; and the PPARgamma; agonist troglitazone at concentrations that reduced cellular lipid content did not alter cell death. High concentrations of troglitazone, however, induced cell death. In summary, SA is a potent inducer of cardiac cell death and intracellular lipid accumulation. The amount of intracellular lipid, however, is not a determinant of cardiomyocyte cell death. Troglitazone has potential cardiotoxicity at high doses but, at lower concentrations, does not prevent cardiac lipotoxicity, which can be completely prevented by low concentrations of oleic acid.
Rabkin
Simon W
SW
University of British Columbia, 9th Floor, 2775 Laurel Street, Vancouver, BC V5Z1M9, Canada. rabkin@interchange.ubc.ca
Lodhia
Parth
P
Lodha
Parth
P
D000818:Animals; D016923:Cell Death / Q000187:drug effects*; D002642:Chick Embryo; D002839:Chromans / Q000494:pharmacology*; D003652:Decanoic Acids / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects*; D009829:Oleic Acids / Q000494:pharmacology*; D013229:Stearic Acids / Q000633:toxicity*; D013778:Tetrazolium Salts; D013844:Thiazoles; D045162:Thiazolidinediones / Q000494:pharmacology*; D000077288:Troglitazone
D002839:Chromans; D003652:Decanoic Acids; D009829:Oleic Acids; D013229:Stearic Acids; D013778:Tetrazolium Salts; D013844:Thiazoles; D045162:Thiazolidinediones; C031183:stearic acid; C031071:decanoic acid; C022616:thiazolyl blue; D000077288:Troglitazone