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Metabolic characterization of volume overload heart failure due to aorto-caval fistula in rats

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Abstract

Metabolic interactions between adipose tissue and the heart may play an active role in progression of heart failure (HF). The aim of the study was to examine changes in myocardial and adipose tissue metabolism and gene expression in a rat HF model induced by chronic volume overload. HF was induced by volume overload from aorto-caval fistula (ACF) in 3-month-old male Wistar rats and animals were studied in the phase of decompensated HF (22nd week). HF rats showed marked eccentric cardiac hypertrophy, pulmonary congestion, increased LV end-diastolic pressure, and intraabdominal fat depletion. HF rats had preserved glucose tolerance, but increased circulating free fatty acids (FFA) and attenuated insulin response during oral glucose challenge. Isolated organ studies showed preserved responsiveness of adipose tissue lipolysis and lipogenesis to epinephrine and insulin in ACF. The heart of HF animals had markedly reduced triglyceride content (almost to half of controls), attenuated anti-oxidative reserve (GSH/GSSG), upregulated HF markers (ANP, periostin, thrombospondin-4), specific signaling pathways (Wnt, TGF-β), and downregulated enzymes of mitochondrial fatty acid oxidation, citric acid cycle, and respiratory chain. Adipose tissue transcription profiling showed upregulated receptor for gastric inhibitory polypeptide. In conclusion, ACF-induced HF model displays several deregulations of systemic metabolism. Despite elevation of systemic FFAs, myocardial triglycerides are low and insulin levels are attenuated, arguing against a role of lipotoxicity or insulin resistance in this model. Attenuated postprandial insulin response and relative lack of its antilipolytic effects may facilitate intraabdominal fat depletion observed in ACF-HF animals.

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Acknowledgments

This study was supported by Ministry of Heath [MZO-00023001 to V.M. and L.C., IGA MZCR NS-10300-3 to J.P., NS10497-3/2009 to V.M.]; Ministry of Education [MSMT-1MO510 to V.M., J.B. and L.C., VZ 0021620806 to D.S., 0021620806 to J.P., 1M6837805002 to H.S. and M.K.]; the Grant agency [305/09/1390 to V.M.]; and the Academy of sciences [AV0Z50520514 to H.S. and M.K, AV0Z50110509 to D.S.] of the Czech Republic.

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Authors and Affiliations

  1. Department of Cardiology and Center for Cardiovascular Research, Institute for Clinical and Experimental Medicine—IKEM, Prague, Czech Republic

    Jan Benes

  2. Center for Cardiovascular Research, Institute for Clinical and Experimental Medicine—IKEM, Prague, Czech Republic

    Petra Skaroupkova & Ludek Cervenka

  3. Department of Experimental Medicine, Institute for Clinical and Experimental Medicine—IKEM, Prague, Czech Republic

    Olena Oliyarnyk & Ludmila Kazdova

  4. Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic

    David Sedmera & Frantisek Papousek

  5. Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic

    Hynek Strnad, Michal Kolar & Cestmir Vlcek

  6. First Faculty of Medicine, Institute of Pathological Physiology, Charles University, Prague, Czech Republic

    Jiri Petrak

  7. First Faculty of Medicine, Institute of Anatomy, Charles University, Prague, Czech Republic

    David Sedmera & Jiri Benes Jr

  8. Second Faculty of Medicine, Department of Physiology, Division of Physiology, Charles University, Prague, Czech Republic

    Ludek Cervenka

  9. Department of Cardiology and Center for Cardiovascular Research, Institute for Clinical and Experimental Medicine—IKEM, Videnska 1958/9, Prague 4, 140 21, Czech Republic

    Vojtech Melenovsky

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  1. Vojtech Melenovsky
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Melenovsky, V., Benes, J., Skaroupkova, P. et al. Metabolic characterization of volume overload heart failure due to aorto-caval fistula in rats. Mol Cell Biochem 354, 83–96 (2011). https://doi.org/10.1007/s11010-011-0808-3

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