title: Cardiomyocyte lipotoxicity is mediated by Il-6 and causes down-regulation of PPARs.
abstract: Here we sought to evaluate the effect of palmitate on cytokine and PPAR activity/expression. We investigated the effect of BSA conjugated palmitate and oleate on PPAR activity, PPAR-α and δ expression, as well as the expression of cytokines and key factors responsible for β-oxidation by qRT-PCR and western blotting in primary rat neonatal cardiomyocytes (NCMs). Furthermore we evaluated the effect of anti-inflammatory actions of AICAR and PPAR agonists on cytokine expression and cell death in palmitate treated NCMs. We found that palmitate caused down regulation of PPARs and increased cytokine expression and cell death, all of which was significantly attenuated by the co-administration of either AICAR or PPAR agonists. This work supports the pro-inflammatory actions of intracellular lipid and provides further insight into the pathological mechanism of cardiac lipotoxicity as occurs in diabetic hearts.
authors.affiliation: Montreal Heart Institute, Université de Montréal, Canada; Department of Medicine, Université de Montréal, Canada.
authors.forename: Taha
authors.initials: T
authors.lastname: Haffar
authors.affiliation: Montreal Heart Institute, Université de Montréal, Canada.
authors.forename: Félix-Antoine
authors.initials: FA
authors.lastname: Bérubé-Simard
authors.affiliation: Montreal Heart Institute, Université de Montréal, Canada; Department of Surgery, Université de Montréal, Canada. Electronic address: nicolas.bousette@umontreal.ca.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bousette
mesh_terms: D000108:Acetylcarnitine / Q000819:agonists / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000187:drug effects; D015850:Interleukin-6 / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D019301:Oleic Acid / Q000494:pharmacology / Q000633:toxicity; D047493:PPAR alpha / Q000819:agonists / Q000378:metabolism*; D047494:PPAR delta / Q000819:agonists / Q000378:metabolism*; D010168:Palmitates / Q000494:pharmacology* / Q000633:toxicity; D011743:Pyrimidines / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D013844:Thiazoles / Q000494:pharmacology
chemical_list: D016207:Cytokines; C425931:GW 501516; D015850:Interleukin-6; D047493:PPAR alpha; D047494:PPAR delta; D010168:Palmitates; D011743:Pyrimidines; D013844:Thiazoles; D019301:Oleic Acid; D000108:Acetylcarnitine; C006253:pirinixic acid; D002334:Carnitine O-Palmitoyltransferase
keywords: Cardiomyocytes; Cytokines; Fatty acids; Lipotoxicity; PPARs