EYES2024 ESE Young Endocrinologists and Scientists (EYES) 2024 Diabetes, Obesity and Metabolism (13 abstracts)
An animal model for heart failure with preserved ejection fraction (HFpEF)
Palina Zytner 1,2 , Niklas Geiger 1,2 , Jan Federspiel 3 , Simon Kloock 1 , Jana Gerner 2 , Aisha-Nike Landthaler 2 , Alexander Georg Nickel 2 , Michael Kohlhaas 2 , Christoph Maack 2 , Andreas Geier 4 , Martin Fassnacht 1 & Ulrich Dischinger & 2
1University Hospital Wuerzburg, Department of Internal Medicine, Division of Endocrinology and Diabetes, Wuerzburg, Germany; 2University Hospital Wuerzburg, Comprehensive Heart Failure Center, Wuerzburg, Germany; 3University Hospital Homburg, Pathology, Homburg, Germany; 4University Hospital Wuerzburg, Hepatology, Wuerzburg, Germany
Introduction: A strong association exists between obesity and heart failure with preserved ejection fraction (HFpEF). Obesity, usually induced by a high-fructose/high-fat Western diet, is one of the main causes of HFpEF. Here, we compare the cardiac and metabolic effects of different diets in combination with the NO-synthase inhibitor L-NAME (LN) in male Wistar rats.
Methods: Male Wistar rats were randomized into the following groups (n = 6, all receiving L-NAME via drinking water): standard diet (standard), a high fructose but low fat diet (LFD) or a high fructose/high fat diet (HFD). An additional group was fed a standard diet without L-NAME (standard without LN). After 16 weeks, blood and heart samples were harvested. Cardiomyocytes as well as mitochondria were isolated. Sarcomere length, cytosolic Ca2+, and mitochondrial redox state, membrane potential and ROS in myocytes were measured using a manual and an automatic Ionoptix fluorescence setup. In isolated mitochondria, mitochondrial respiration, membrane potential, Ca2+-retention capacity and H2O2 production were examined.
Results: A substantial increase in plasma BNP (P < 0.001), diastolic dysfunction with preserved fractional shortening, increased diastolic and systolic and Ca2+ transient amplitude was observed only in the HFD group compared to standard without LN. The mitochondrial redox state of HFD group was oxidized, while mitochondrial membrane potential was more stable vs standard and vs LFD in the presence of pyruvate/malate, but not fatty acids. Independent of the given substrate, Ca2+-retention capacity and H2O2 production were not different between groups.
Conclusion: Only the combined treatment of a high fructose/high fat diet and L-NAME is sufficient to generate calcium mishandling and mitochondrial dysfunction typical for HFpEF. Overall, this model promises to be a valid model for examining the effects of HFpEF and, beyond that, the effects of anti-obesity drugs.
Volume 102
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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