ALTERATIONS IN SUBSTRATE METABOLISM IN EXPERIMENTAL HEART FAILURE ARE ASSOCIATED WITH INTRAABDOMINAL FAT DEPLETION AND POSTPRANDIAL HYPOINSULINEMIA | XVIII. výroční sjezd České kardiologické společnosti

Goal: Abnormalities in substrate metabolism may play a role in progression of chronic heart failure (HF). The goal of the study was to examine the extent and mechanisms of metabolic alterations in rat model of HF due to volume overload.
Methods and Results: 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 cardiomegaly, pulmonary congestion, increased LV end-diastolic pressure and intraabdominal fat depletion (-33% epididymal fat pad/BW). HF rats had preserved glucose tolerance, but increased circulating free fatty acids (FFA) and attenuated insulin response during oral glucose challenge (-63% and -68% at 60´ and 120´). Isolated organ incubation showed preserved responsiveness of fat tissue lipolysis and lipogenesis to catecholamines and insulin, but attenuated muscle substrate oxidation and insulin responsiveness in HF animals. Fat transcription profile (Illumina) showed upregulated receptor for incretin gastric inhibitory peptide (GIPR). The heart of HF animals had reduced triglyceride content (-53%) and anti-oxidative reserve (GSH/GSSG), upregulated HF markers (ANP, periostin, thrombospondin 4) and downregulation metabolic pathways of mitochondrial fatty acid metabolism, Krebs cycle and respiratory chain.
Conclusion: HF animals showed multiple abnormalities of substrate metabolism typical for human HF. Despite high circulating FFA and downregulated genes of fatty acid metabolism, triglyceride content was reduced in HF hearts, arguing against the role of lipotoxicity. Attenuated postprandial insulin response and relative lack of its antilipolytic effects may facilitate intraabdominal fat tissue loss seen in HF animals and may be relevant in development of cardiac cachexia.

ALTERATIONS IN SUBSTRATE METABOLISM IN EXPERIMENTAL HEART FAILURE ARE ASSOCIATED WITH INTRAABDOMINAL FAT DEPLETION AND POSTPRANDIAL HYPOINSULINEMIA Tématický okruh: Srdeční selhání, transplantace, oběhové podpory
Typ: Ústní sdělení - lékařské , Číslo v programu: 471


Melenovský V.¹, Škaroupková P.², Beneš J.², Kazdová L.², Strnad H.³, Kolář M.³, Červenka L.² ¹ Klinika kardiologie, IKEM, Praha, ² Center for cardiovascular research, IKEM, Praha, ³ Institute of Molecular Genetics, AV CR, Praha
Goal: Abnormalities in substrate metabolism may play a role in progression of chronic heart failure (HF). The goal of the study was to examine the extent and mechanisms of metabolic alterations in rat model of HF due to volume overload. Methods and Results: 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 cardiomegaly, pulmonary congestion, increased LV end-diastolic pressure and intraabdominal fat depletion (-33% epididymal fat pad/BW). HF rats had preserved glucose tolerance, but increased circulating free fatty acids (FFA) and attenuated insulin response during oral glucose challenge (-63% and -68% at 60´ and 120´). Isolated organ incubation showed preserved responsiveness of fat tissue lipolysis and lipogenesis to catecholamines and insulin, but attenuated muscle substrate oxidation and insulin responsiveness in HF animals. Fat transcription profile (Illumina) showed upregulated receptor for incretin gastric inhibitory peptide (GIPR). The heart of HF animals had reduced triglyceride content (-53%) and anti-oxidative reserve (GSH/GSSG), upregulated HF markers (ANP, periostin, thrombospondin 4) and downregulation metabolic pathways of mitochondrial fatty acid metabolism, Krebs cycle and respiratory chain. Conclusion: HF animals showed multiple abnormalities of substrate metabolism typical for human HF. Despite high circulating FFA and downregulated genes of fatty acid metabolism, triglyceride content was reduced in HF hearts, arguing against the role of lipotoxicity. Attenuated postprandial insulin response and relative lack of its antilipolytic effects may facilitate intraabdominal fat tissue loss seen in HF animals and may be relevant in development of cardiac cachexia.

PROHLÍŽENÍ ABSTRAKTA