title: Metabolic characterization of volume overload heart failure due to aorto-caval fistula in rats.
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.
authors.affiliation: 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@ikem.cz
authors.forename: Vojtech
authors.initials: V
authors.lastname: Melenovsky
authors.forename: Jan
authors.initials: J
authors.lastname: Benes
authors.forename: Petra
authors.initials: P
authors.lastname: Skaroupkova
authors.forename: David
authors.initials: D
authors.lastname: Sedmera
authors.forename: Hynek
authors.initials: H
authors.lastname: Strnad
authors.forename: Michal
authors.initials: M
authors.lastname: Kolar
authors.forename: Cestmir
authors.initials: C
authors.lastname: Vlcek
authors.forename: Jiri
authors.initials: J
authors.lastname: Petrak
authors.forename: Jiri
authors.initials: J
authors.lastname: Benes
authors.forename: Frantisek
authors.initials: F
authors.lastname: Papousek
authors.forename: Olena
authors.initials: O
authors.lastname: Oliyarnyk
authors.forename: Ludmila
authors.initials: L
authors.lastname: Kazdova
authors.forename: Ludek
authors.initials: L
authors.lastname: Cervenka
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001011:Aorta / Q000601:surgery; D001164:Arteriovenous Fistula; D001166:Arteriovenous Shunt, Surgical; D015415:Biomarkers / Q000378:metabolism; D004822:Epididymis / Q000378:metabolism / Q000473:pathology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D020869:Gene Expression Profiling; D005951:Glucose Tolerance Test; D005978:Glutathione / Q000378:metabolism; D006321:Heart / Q000503:physiopathology*; D006333:Heart Failure / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006439:Hemodynamics; D007328:Insulin / Q000097:blood; D007668:Kidney / Q000473:pathology; D050356:Lipid Metabolism; D008099:Liver / Q000473:pathology; D008168:Lung / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D009929:Organ Size; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014684:Venae Cavae / Q000601:surgery; D020257:Ventricular Remodeling
chemical_list: D015415:Biomarkers; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D017392:Thiobarbituric Acid Reactive Substances; D013482:Superoxide Dismutase; D005978:Glutathione