title: Interleukin 6 modulates PPARα and PGC-1α and is involved in high-fat diet induced cardiac lipotoxicity in mouse.
abstract: BACKGROUND
  Interleukin 6 (IL-6) may be involved in regulation of cardiac lipid metabolism and mitochondrial function through its influence on peroxisome proliferator-activated receptors (PPARs). In this study we evaluated the impact of the physiological level of IL-6 on the expression of PPARα and PGC-1α in the heart and the effect of lack of this cytokine on high-fat diet (HFD) induced lipotoxicity.
  
  
  METHODS
  Male C57BL6/J wild type (WT) and IL-6 knock-out (IL-6KO) mice were used. 20 animals of each genotype were fed with HFD for 15-18weeks. Cardiac function was assessed using echocardiography and cardiomyocyte ultrastructure was examined using electron microscopy. QT-PCR and Western blotting were applied to estimate the expression of PPARα and PGC-1α at the transcriptional and protein levels.
  
  
  RESULTS
  At baseline WT and IL-6KO mice had similar size and function of the left ventricle. HFD induced similar left ventricular hypertrophic response in both groups without causing heart failure, but only WT animals had increased resting ejection fraction of the LV. Ultrastructure of HFD groups showed markers of lipotoxicity, that were more pronounced in IL-6KO group. In basal conditions IL-6KO animals had lower PPARα and similar PGC-1α expression as compared to WT. HFD induced downregulation of both PPARα and PGC-1α in WT animals, while in IL-6KO mice this effect was constrained.
  
  
  CONCLUSIONS
  IL-6 is involved in basal regulation of PPARα and PGC-1α expression in cardiomyocytes. The lack of this cytokine promotes high-fat diet induced lipotoxicity but without overt manifestations of cardiac failure.
authors.affiliation: Department of General and Experimental Pathology, Medical University of Bialystok, Bialystok, Poland. Electronic address: Tomasz.Bonda@umb.edu.pl.
authors.forename: Tomasz A
authors.initials: TA
authors.lastname: Bonda
authors.affiliation: Department of Histology and Embryology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Szynaka
authors.affiliation: Department of General and Experimental Pathology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Sokołowska
authors.affiliation: Department of General and Experimental Pathology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Dziemidowicz
authors.affiliation: Department of Cardiology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Waszkiewicz
authors.affiliation: Department of General and Experimental Pathology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Winnicka
authors.affiliation: Department of Medical Pathomorphology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Bernaczyk
authors.affiliation: Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Natalia
authors.initials: N
authors.lastname: Wawrusiewicz-Kurylonek
authors.affiliation: Department of Cardiology, Medical University of Bialystok, Bialystok, Poland; Department of Population Medicine and Civilization Diseases Prevention, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Karol A
authors.initials: KA
authors.lastname: Kamiński
mesh_terms: D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D015850:Interleukin-6 / Q000172:deficiency* / Q000502:physiology; D050356:Lipid Metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D047493:PPAR alpha / Q000096:biosynthesis*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000096:biosynthesis*; D011897:Random Allocation
chemical_list: D015850:Interleukin-6; D047493:PPAR alpha; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse
keywords: Heart; High fat diet; Lipotoxicity; Mouse; PGC-1α; PPARα