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Updated: Jun 3, 2026
A Rat Model of Pressure Overload Induced Moderate Remodeling and Systolic Dysfunction as Opposed to Overt Systolic Heart Failure
Published on: April 30, 2020
Metabolic characterization of volume overload heart failure due to aorto-caval fistula in rats
Vojtech Melenovsky1, Jan Benes, Petra Skaroupkova
1Department 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
Insights
Heart failure (HF) involves metabolic changes in fat and heart tissue. This study in a rat model shows altered fat metabolism and reduced heart triglycerides, suggesting complex interactions in HF progression.
Area of Science:
- Cardiovascular Metabolism
- Molecular Cardiology
- Adipose Tissue Biology
Background:
- Metabolic crosstalk between adipose tissue and the heart is implicated in heart failure (HF) progression.
- Understanding these interactions is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate metabolic and gene expression changes in cardiac and adipose tissues during chronic volume overload-induced HF in rats.
- To elucidate the role of metabolic dysregulation in the pathophysiology of decompensated HF.
Main Methods:
- Induction of HF via aorto-caval fistula (ACF) in Wistar rats, studied at the decompensated phase (22nd week).
- Assessment of cardiac structure, function, systemic glucose/lipid metabolism, and isolated organ function (adipose tissue lipolysis/lipogenesis).
- Analysis of myocardial gene/protein expression for HF markers, signaling pathways, and metabolic enzymes; adipose tissue transcription profiling.
Main Results:
- ACF rats exhibited cardiac hypertrophy, pulmonary congestion, and intraabdominal fat depletion.
- Preserved glucose tolerance but elevated circulating free fatty acids (FFA) and attenuated insulin response were observed.
- Myocardial triglycerides were reduced, anti-oxidative reserve attenuated, HF markers and specific signaling pathways upregulated, and mitochondrial fatty acid oxidation enzymes downregulated.
- Adipose tissue showed preserved responsiveness but upregulated gastric inhibitory polypeptide receptor.
Conclusions:
- The ACF-induced HF model demonstrates significant systemic metabolic derangements.
- Low myocardial triglycerides and attenuated insulin levels argue against direct lipotoxicity or insulin resistance in this model.
- Impaired postprandial insulin response and reduced antilipolytic effects may contribute to fat depletion in ACF-HF.
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.
