ECEESPE2025 Poster Presentations MTEabolism, Nutrition and Obesity (125 abstracts)
Sex-specific effects of different dietary compositions and NO-synthase inhibition on mitochondrial respiration and cellular redox state in HFPEF and MASLD
Palina Zytner 1 , Michael Kohlhaas 2 , Alexander Nickel 2 , Niklas Geiger 1 , Viktoria Kenner 2 , Mia Külzer 2 , Jana Gerner 2 , Aisha Landthaler 2 , Maria Popp 2 , Annika Engelhardt 2 , Christoph Maack 2 , Vasco Sequeira 2 & Ulrich Dischinger 1
1University Hospital of Würzburg, Würzburg, Germany; 2Comprehensive Heart Failure Center, Würzburg, Germany
JOINT3930
Background: Obesity is closely linked to heart failure with preserved ejection fraction (HFpEF) and metabolic-dysfunction associated steatotic liver disease (MASLD). A model combining diet-induced obesity with L-NAME–induced hypertension may replicate HFpEF and MASLD conditions effectively. However, the optimal dietary composition and duration for inducing these diseases remain uncertain. This study evaluates the impact of various diets combined with L-NAME, a pan-nitric oxide synthase inhibitor, on HFpEF and MASLD characteristics in male and female Wistar rats.
Methods: Male and female Wistar rats were assigned to receive either standard chow (CO), standard chow with L-NAME, low-fat diet (LFD+L-NAME), or high-fat, high-fructose diet (HFD) with or without L-NAME. HFD groups had ad libitum access to HFD or LFD. Isolated cardiomyocytes were evaluated for mitochondrial redox state. Isolated cardiac and hepatic mitochondria were subjected to high-resolution respirometry to assess oxygen consumption and ROS emission.
Results: In male rats, the HFD group exhibited an oxidized cardiac mitochondrial redox state, indicative of increased metabolic demand compared to CO, while effects of LFD and L-NAME alone were less visible. Cardiac mitochondrial respiration was effectively impared in the HFD group. In contrast, hepatic mitochondrial respiration was significantly elevated in the HFD group compared to CO but only partially affected by LFD and L-NAME. In females, the mitochondrial redox state was more reduced across all conditions compared to CO, indicating lower mitochondrial demand or increased metabolic redundancy. Mitochondrial respiration was paradoxically elevated in all intervention groups compared to controls. Hepatic mitochondria from the HFD group exhibit significantly more oxygen compared to CO.
Conclusions: The combination of HFD and L-NAME induces HFpEF and MASLD characteristics with distinct sex-specific effects. This investigation is crucial for developing future therapeutic strategies and underscores the importance of analyzing sex-specific differences, which can significantly influence treatment outcomes in patients with HFpEF and MASLD.
Volume 110
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Endocrine Abstracts
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