bims-hafaim Biomed News
on Heart failure metabolism
Issue of 2026–01–04
two papers selected by
Kyle McCommis, Saint Louis University
  1. DPP-4 inhibitor linagliptin modulates myocardial metabolism in a model of coronary artery disease.
  2. A simple, anesthesia-free infusion technique for in vivo metabolic tracing.
  1. JTCVS Open. 2025 Dec;28 262-275
    DPP-4 inhibitor linagliptin modulates myocardial metabolism in a model of coronary artery disease.
    Kelsey C Muir, Dwight D Harris, Christopher Stone, Meghamsh Kanuparthy, Jad Hamze, Frank W Sellke.
       Objective: Coronary artery disease (CAD) remains a leading public health concern in the United States. Dipeptidyl peptidase-4 inhibitors, such as linagliptin, have demonstrated cardioprotective effects in preclinical studies; however, their influence on myocardial metabolic changes remains incompletely characterized. Our study aimed to evaluate the effects of linagliptin, as it influences incretin hormones, on myocardial metabolism and substrate utilization in a clinically relevant model of CAD.
    Methods: Eleven-week-old Yorkshire swine underwent placement of an ameroid constrictor to the proximal left circumflex coronary artery to induce chronic myocardial ischemia. After 2 weeks to ensure ameroid closure, swine were divided into a group that received daily oral linagliptin treatment for 5 weeks (n = 8) and a group that received no drug treatment (n = 8) for 5 weeks. After 5 weeks, the swine underwent a terminal harvest procedure and subsequent immunoblotting and proteomic analysis.
    Results: Linagliptin was associated with reduced fatty acid oxidation on proteomic pathway analysis and decreased expression of carnitine palmitoyltransferase 1 beta (CPT1β) (P = .0014) and CPT1α (P = .02) on immunoblotting. Treatment resulted in strict regulation of glycolysis and increased expression of proteins involved in ketone metabolism and the glycerophosphate shuttle. Additionally, linagliptin enhanced protein expression of several citric acid enzymes and significantly regulated protein expression relating to oxidative stress within the ischemic myocardium.
    Conclusions: Linagliptin shifted myocardial metabolism pointing to enhanced ketone utilization, upregulation of the TCA cycle, and reductions in free fatty acid oxidation, glycolysis, and lactate production. These findings suggest a potential cardioprotective role for linagliptin via metabolic manipulation under ischemic conditions, warranting further investigation.
    Keywords:  coronary artery disease; dipeptidyl peptidase 4 inhibitors; linagliptin; mitochondrial oxidation; myocardial metabolism
    DOI:  https://doi.org/10.1016/j.xjon.2025.09.007
  2. bioRxiv. 2025 Dec 19. pii: 2025.12.17.694756. [Epub ahead of print]
    A simple, anesthesia-free infusion technique for in vivo metabolic tracing.
    Yumi Kim, Samantha Caldwell, Meredith Long, Dominique Abrahams, Margi Baldwin, Gina M DeNicola.
      Accurate metabolic flux analysis requires tracer delivery that preserves physiological metabolism. Current methods may distort metabolism through anesthesia, surgical stress, or complex procedures. We demonstrate that isoflurane anesthesia profoundly alters serum and tissue metabolism across multiple pathways. Glycolytic and TCA cycle intermediates, sulfur and aromatic amino acid metabolites, acylcarnitines, and nucleotide pools decreased, while branched-chain amino acids, their ketoacids, ketone bodies, and fatty acids increased. These coordinated changes were suggestive of mitochondrial complex I inhibition and reduced oxidative catabolism, leading to shifts in metabolite pool sizes that compromise isotopologue-based flux interpretation. We established a tail vein catheterization method completed in minutes under brief anesthesia that enables multi-hour tracer infusion in awake, freely moving mice. This method achieved steady-state labeling of cystine and downstream products comparable to jugular infusion without supraphysiologic cystine accumulation. This platform provides a practical, physiologically accurate method for in vivo steady-state isotope tracing.
    DOI:  https://doi.org/10.64898/2025.12.17.694756
This page is being maintained by Thomas Krichel. It was last updated on 2026‒01‒05 at 15:55.