bims-hafaim Biomed News
on Heart failure metabolism
Issue of 2025–08–24
two papers selected by
Kyle McCommis, Saint Louis University



  1. JACC Basic Transl Sci. 2025 Aug 15. pii: S2452-302X(25)00286-4. [Epub ahead of print]10(9): 101334
      Heart failure with preserved ejection fraction (HFpEF) accounts for ∼50% of HF cases. The ZSF1-obese rat model recapitulates clinical features of HFpEF including hypertension, obesity, metabolic syndrome, exercise intolerance, and diastolic dysfunction. We utilized a systems-biology approach to define the metabolic and transcriptional signatures to gain mechanistic insight into pathways contributing to HFpEF development. Male ZSF1-obese, ZSF1-lean hypertensive controls, and WKY (wild-type) controls were compared at 14 weeks of age for extensive physiological phenotyping and left ventricle (LV) tissue harvesting for unbiased-metabolomics, RNA-sequencing, and mitochondrial morphology and function. Utilizing ZSF1-lean and WKY controls enabled a distinction between hypertension-driven molecular changes driving HFpEF pathology, versus hypertension + metabolic syndrome. Comparison of ZSF1-lean vs WKY (ie, hypertension-exclusive effects) revealed metabolic remodeling suggesting increased aerobic glycolysis, decreased β-oxidation, and dysregulated purine and pyrimidine metabolism with few transcriptional changes. ZSF1-obese rats displayed worsened metabolic remodeling and robust transcriptional remodeling highlighted by upregulation of inflammatory genes and downregulation of the mitochondrial structure/function and metabolic processes. Integrated network analysis of metabolomic and RNAseq datasets revealed downregulation of most catabolic energy producing pathways, manifesting in a marked decrease in the energetic state (ie, reduced ATP/ADP, PCr/ATP). Cardiomyocyte ultrastructure analysis revealed decreased mitochondrial area, size, and cristae density, as well as increased lipid droplet content in HFpEF hearts. Impaired mitochondrial function was demonstrated by decreased substrate-mediated respiration and dysregulated calcium handling. Collectively, the integrated omics approach applied here provides a framework to uncover novel genes, metabolites, and pathways underlying HFpEF, with an emphasis on mitochondrial energy metabolism as a potential interventional target.
    Keywords:  HFpEF; cardiac remodeling; heart failure; metabolism; mitochondria
    DOI:  https://doi.org/10.1016/j.jacbts.2025.101334
  2. Diabetol Metab Syndr. 2025 Aug 18. 17(1): 336
      The global prevalence of obesity is rapidly in creasing, significantly increasing the incidence of heart failure with preserved ejection fraction (HFpEF). Obesity, one of the most common clinical phenotypes of HFpEF, facilitates the onset and progression of HFpEF via multiple pathophysiological mechanisms. Lifestyle intervention, which serves as the cornerstone of weight loss, plays a crucial role in the management of HFpEF. Novel antidiabetic therapies, including sodium glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1 RA), and glucose‒dependent insulinotropic polypeptide (GIP)/glucagon‒like peptide-1 (GLP-1) dual receptor agonists, have favourable effects on clinical outcomes in obese HFpEF patients. For patients with heart failure (HF) prior to bariatric surgery (BSx), there is moderate evidence supporting the efficacy and safety of the procedure. This review systematically summarizes the clinical evidence related to metabolic therapy treatment strategies for obese HFpEF patients and discusses the potential advantages of such therapy.
    Keywords:  Bariatric surgery; GIP/GLP-1 dual receptor agonists; GLP-1 RA; HFpEF; Lifestyle intervention; Obesity; SGLT2i
    DOI:  https://doi.org/10.1186/s13098-025-01917-z