# Impact and regulation of lactate metabolism in the heart

> **NIH NIH K99** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2024 · $110,677

## Abstract

Project Summary/Abstract
The heart has a distinct metabolism that supports the continuous pumping of blood. This includes maintaining
the pyruvate-lactate axis.
This metabolic axis describes the interrelation between three critical metabolic nodes:
central carbon metabolism in the cytoplasm, oxidative phosphorylation in the mitochondria, and lactate
abundance in the extracellular milieu.
During heart failure, this metabolic axis is imbalanced by increased
glycolytic flux coupled to decreased pyruvate oxidation and increased lactate export. In newly published data, I
demonstrated that inhibiting lactate export in the heart, was sufficient to rebalance this axis and mitigate cardiac
hypertrophy and heart failure in mice. Suggesting that retaining lactate within the heart is beneficial to its health.
This is further supported by the fact that healthy hearts are net consumers of lactate. Yet, lactate metabolism
remains ill-defined and poorly studied within the heart. This proposal seeks to quantitatively characterize lactate
metabolism in the heart and to test the hypothesis that myocardial lactate production and consumption is integral
to cardiac health by balancing and maintaining the pyruvate-lactate axis in the heart. In my K99 Aim 1, I will use
isotope tracers to quantify lactate production and consumption fluxes in normal cardiomyocytes and hearts. In
my K99 Aim 2, I will define the metabolic rewiring of the pyruvate-lactate axis in chronic heart failure patients
undergoing left ventricle assist device (LVAD) therapy that have been infused with 13C-glucose and compare
failing and recovering human hearts. I will also infuse HF mouse models with 13C-glucose and treat them with
the MCT4 inhibitor VB124, to determine if VB124 is a suitable treatment for LVAD HF patients. In my R00 Aim3,
I will build a research program centered around comprehensively understanding how lactate metabolism is
regulated, and how it impacts hypertrophic cardiomyopathy (HCM). Collectively, these experiments will lay the
groundwork for targeting of lactate metabolism as a new therapeutic approach in cardiac hypertrophy and heart
failure. Under the guidance of my primary mentor, Co-mentor and my team of collaborators during the K99
period, this proposal will allow me to successfully transition from my current mentored position into an
independent research group leader.

## Key facts

- **NIH application ID:** 10896965
- **Project number:** 5K99HL168312-02
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Ahmad A Cluntun
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $110,677
- **Award type:** 5
- **Project period:** 2023-08-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10896965

## Citation

> US National Institutes of Health, RePORTER application 10896965, Impact and regulation of lactate metabolism in the heart (5K99HL168312-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10896965. Licensed CC0.

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