Tomasz A Bonda1, Beata Szynaka2, Magdalena Sokołowska3, Magdalena Dziemidowicz3, Ewa Waszkiewicz4, Maria M Winnicka3, Piotr Bernaczyk5, Natalia Wawrusiewicz-Kurylonek6, Karol A Kamiński7. 1. Department of General and Experimental Pathology, Medical University of Bialystok, Bialystok, Poland. Electronic address: Tomasz.Bonda@umb.edu.pl. 2. Department of Histology and Embryology, Medical University of Bialystok, Bialystok, Poland. 3. Department of General and Experimental Pathology, Medical University of Bialystok, Bialystok, Poland. 4. Department of Cardiology, Medical University of Bialystok, Bialystok, Poland. 5. Department of Medical Pathomorphology, Medical University of Bialystok, Bialystok, Poland. 6. Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland. 7. Department of Cardiology, Medical University of Bialystok, Bialystok, Poland; Department of Population Medicine and Civilization Diseases Prevention, Medical University of Bialystok, Bialystok, Poland.
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. CONCLUSION: 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.
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. CONCLUSION: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: Magdalena Dziemidowicz; Tomasz A Bonda; Siergiej Litvinovich; Andrzej Taranta; Maria M Winnicka; Karol A Kamiński Journal: Arch Med Sci Date: 2019-11-03 Impact factor: 3.318