title: Hyperthyroidism evokes myocardial ceramide accumulation.
abstract: BACKGROUND
  Thyroid hormones (THs) are key regulators of cardiac physiology as well as modulators of different cellular signals including the sphingomyelin/ceramide pathway. The objective of this study was to examine the effect of hyperthyroidism on the metabolism of sphingolipids in the muscle heart.
  
  
  METHODS
  Male Wistar rats were treated for 10 days with triiodothyronine (T3) at a dose of 50µg/100g of body weight. Animals were then anaesthetized and samples of the left ventricle were excised.
  
  
  RESULTS
  We have demonstrated that prolonged, in vivo, T3 treatment increased the content of sphinganine (SFA), sphingosine (SFO), ceramide (CER) and sphingomyelin (SM), but decreased the level of sphingosine-1-phosphate (S1P) in cardiac muscle. Accordingly, the changes in sphingolipids content were accompanied by a lesser activity of neutral sphingomyelinase and without significant changes in ceramidases activity. Hyperthyroidism also induced activation of AMP-activated protein kinase (AMPK) with subsequently increased expression of mitochondrial proteins: cytochrome c oxidase IV (COX IV), β-hydroxyacyl-CoA dehydrogenase (β-HAD), carnityne palmitoyltransferase I (CPT I) and nuclear peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α).
  
  
  CONCLUSIONS
  We conclude that prolonged T3 treatment increases sphingolipids metabolism which is reflected by higher concentration of SFA and CER in heart muscle. Furthermore, hyperthyroidism-induced increase in heart sphingomyelin (SM) concentration might be one of the mechanisms underlying maintenance of CER at relatively low level by its conversion to SM together with decreased S1P content.
authors.affiliation: Department of Physiology, Medical University of Białystok, Białystok, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Mikłosz
authors.forename: Bartłomiej
authors.initials: B
authors.lastname: Łukaszuk
authors.forename: Adrian
authors.initials: A
authors.lastname: Chabowski
authors.forename: Filip
authors.initials: F
authors.lastname: Rogowski
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kurek
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Żendzian-Piotrowska
mesh_terms: D000818:Animals; D055572:Ceramidases / Q000378:metabolism; D002518:Ceramides / Q000378:metabolism*; D004195:Disease Models, Animal; D006980:Hyperthyroidism / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism*; D008246:Lysophospholipids / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D013109:Sphingomyelins / Q000378:metabolism*; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism; D014284:Triiodothyronine / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D002518:Ceramides; D008246:Lysophospholipids; D013109:Sphingomyelins; D014284:Triiodothyronine; C060506:sphingosine 1-phosphate; D013108:Sphingomyelin Phosphodiesterase; D055572:Ceramidases; D013110:Sphingosine