What is the clinical evidence from this study?

Study design: Other. Population: Hypertension and pathological cardiac hypertrophy. Intervention: Low-valine diet. Primary outcome: Cardiac hypertrophy and mitochondrial function.

What does this research mean for the field?

A low-valine diet improved mitochondrial function and reduced pathological cardiac hypertrophy in hypertensive models by increasing ATP5F1B expression. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

The aim is to explore how a low-valine diet affects cardiac hypertrophy and its underlying mechanisms.

February 6, 2026

Low-valine diet ameliorates pathological cardiac hypertrophy by inhibiting LONP1-mediated ATP5F1B degradation

Key Result

A low-valine diet ameliorated pathological cardiac hypertrophy and improved mitochondrial function in hypertensive models by inhibiting LONP1-mediated ATP5F1B degradation.

Key Points

The aim is to explore how a low-valine diet affects cardiac hypertrophy and its underlying mechanisms.
Utilized the NHANES database to examine dietary valine intake and cardiovascular disease risk.
Conducted pull-down assays and mass spectrometry to analyze ATP5F1B binding affinities in hypertensive tissues.
Performed immunofluorescence studies to assess ATP5F1B expression changes induced by valine.
Employed in vitro and in vivo approaches to evaluate mitochondrial function and pathology in cardiomyocytes.
A low-valine diet significantly increased ATP5F1B expression and improved mitochondrial function.
Elevated levels of valine were associated with increased LONP1 binding, leading to ATP5F1B degradation.
Reduction in oxidative stress injury was observed alongside improvements in cardiac structure and function.
Key mutations affecting protein binding were identified, with 330A ARG being crucial.

Structured PICO

Does a low-valine diet ameliorate pathological cardiac hypertrophy in hypertension?

Population

Hypertensive animal models, cardiomyocytes in vitro, and human data from the NHANES database

Intervention

Low-valine diet / low valine environment

Comparator

High valine environment / standard diet

Outcome

Pathological cardiac hypertrophy, mitochondrial structure and function, and oxidative stress injurysurrogate

A low-valine diet ameliorates hypertensive pathological cardiac hypertrophy by preserving ATP5F1B expression through the inhibition of LONP1-mediated degradation.

Abstract

Abstract Backgroud An accumulated valine in cardiomyocytes under hypertension is associated with pathological cardiac hypertrophy. Therefore, a low-valine diet may be effective in the amelioration of cardiac hypertrophy. Methods and Results This study utilised the NHANES database to investigate the association between elevated dietary valine intake and the risk of developing cardiovascular disease. Utilising a combination of a L-valine agarose bead construction through a pull-down assay and mass spectrometry analysis, it was ascertained that ATP5F1B exhibited a significant binding affinity for valine in hypertensive cardiac tissues. Moreover, immunofluorescence co-localisation studies elucidated that an augmentation in the concentration of FITC-L-valine led to a diminution in ATP5F1B expression within cardiomyocytes. In vitro and in vivo, it verified that a low-valine diet improved mitochondrial structure and function in cardiomyocytes by increasing ATP5F1B protein expression, reduced oxidative stress injury, and attenuated pathological cardiac hypertrophy in hypertension. Furthermore, through myocardial-specific overexpression and interference with Atp5f1β, it was demonstrated that the valine diet could regulate ATP5F1B expression to affect mitochondrial structural function and oxidative stress, as well as to have an effect on hypertensive pathological cardiac hypertrophy and cardiac function. Co-IP coupled with mass spectrometry analysis revealed that ATP5F1B binding to LONP1 was increased in the high valine environment of cardiomyocytes, and we demonstrated that low valine diet could improve the mitochondrial structural function and reduce oxidative stress injury, and reduce hypertension pathological cardiac hypertrophy and cardiac function. Co-IP confirmed that LONP1 binding to ATP5F1B was reduced and ATP5F1B expression was increased in cardiac tissues of hypertensive animals on a low-valine diet. PDB prediction of the three binding sites revealed mutations in the relevant residues (316A ASP, 328A VAL and 330A ARG), and the construction of mutation sites and in vitro experiments revealed that 330A ARG was the keysite. Conclusions This study investigated the role and molecular mechanism of low-val diet in ameliorating pathological cardiac hypertrophy in hypertension, which constructed at multiple levels, including molecular, cellular and animal.

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Cite This Study

Kuang et al. (Sat,) conducted a other in Hypertension and pathological cardiac hypertrophy. Low-valine diet was evaluated on Cardiac hypertrophy and mitochondrial function. A low-valine diet ameliorated pathological cardiac hypertrophy and improved mitochondrial function in hypertensive models by inhibiting LONP1-mediated ATP5F1B degradation.

synapsesocial.com/papers/698586388f7c464f2300a350 https://doi.org/https://doi.org/10.1093/eurheartj/ehaf784.945

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