LC–MS Profiling Reveals Diet- and Hypertension-Specific Alterations in Amino Acid Metabolism

Although an unhealthy diet and hypertension constitute major risk factors for the development of cardiometabolic diseases, the direct effects of dietary components and high blood pressure on metabolic profiles remain poorly understood. Recently, a team of researchers from the Slovak Academy of Sciences (Bratislava, Slovakia), the Medical University of Warsaw (Poland), and the Polish Academy of Sciences (Warsaw, Poland) examined this issue more closely, analyzing concentrations of amino acids and nutrients in the plasma and tissues of animal models subjected to high-fat and high-disaccharide diet without excessive caloric intake, in salt-resistant rats on high salt intake, in spontaneously hypertensive rats, and in angiotensin II-induced hypertensive rats. Using liquid chromatography (LC) and mass spectrometry (MS), the team identified changes in several analytes across models. A paper based on their work was published in the Journal of Nutrition and Metabolism (1).

A disproportionate intake of saturated fat and simple carbohydrates has been connected to the development of dyslipidemia (unhealthy levels of one or more kinds of lipid in the blood), diabetes, and hypertension (2-4). In their study, the researchers analyzed plasma and tissues of rats on high-fat and high-sugar diets without excessive caloric intake, salt-resistant rats on high salt intake, spontaneously hypertensive rats (SHR), and angiotensin II (Ang II)–induced hypertensive rats by LC–MS. This grouping was designed to evaluate how different diet-induced and genetically predisposed conditions, all associated with metabolic and cardiovascular disturbances, affect amino acid metabolism.

“This approach,” the authors wrote in their article (1), “enables us to identify potential shared or distinct metabolic alterations linked to dietary and hypertensive pathophysiology.”

The researchers discovered that a high-fat diet increased tissue levels of glycine and methylglycine/sarcosine (an amino acids which is an intermediate and byproduct of in glycine synthesis and degradation [5]), while high salt intake and hypertension were associated with a distinct reduction of methyl/glycine species and the accumulation of taurine in the tissues. They also observed tissue-specific alterations. For example, alanine decreased in the kidneys of rats on high salt and in hypertensive models. Beta-alanine was higher in the lung and renal cortex of rats on high salt, but lower in the cardiovascular system of hypertensive models. A high-sugar diet increased circulating levels of betaine and taurine, although its impact on tissues was less pronounced (1).

“Our findings,” the authors of the study write (1), “indicate that diet and hypertension significantly alter the levels of amino acids and nutrients that supply the one-carbon metabolism. We found that high-fat diet increased glycine and its methylated derivatives, while high salt intake and hypertension decreased these species in the organism. A high-sugar diet increased plasmatic betaine and taurine, but the impact on tissue metabolism was minor. To sum up, the changes in organic solutes did not follow a consistent pattern across experimental conditions, reflecting the complexity of metabolic responses to unbalanced diet and hypertension.”

However, the authors acknowledged that their research was limited to descriptive metabolic analysis, and it did not include interventional experiments. They believe that future research should focus on functional approaches, such as supplementation or inhibition of selected amino acids, to determine whether modulating these metabolites can ameliorate hypertension or cardiovascular dysfunction.

“Such studies,” they concluded in their paper (1), “will be essential to establish causal relationships and evaluate the therapeutic potential of amino acid-targeted interventions.”

As a result, the study’s findings showed that high-fat diets increased glycine and methylglycine species, whereas high salt intake and hypertension reduced these metabolites and increased taurine, underscoring the complex and condition-dependent metabolic effects of diet and blood pressure.

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References

1. Smoradkova, K.; Szudzik, M.; Maksymiuk, K. et al. Metabolic Alterations Associated With Diet and Hypertension in Rats. J. Nutr. Metab. 2026, 2026, 6248625. DOI: 10.1155/jnme/6248625
2. Ludwig, D. S.; Willett, W. C.; Volek, J. S. et al. Dietary Fat: From Foe to Friend? Science 2018, 362 (6416), 764-770. DOI: 10.1126/science.aau2096
3. Kearney, P. M.; Whelton, M.; Reynolds, K. et al. Global Burden of Hypertension: Analysis of Worldwide Data. Lancet 2005, 365 (9455), 217-23. DOI: 10.1016/S0140-6736(05)17741-1
4. Dyslipidemia: What You Need to Know. Healthline website.https://www.healthline.com/health/dyslipidemia (accessed 2026-01-09).
5. Sarcosine. Wikipedia.https://en.wikipedia.org/wiki/Sarcosine (accessed 2026-01-09).