LC–MS Profiling of Arterial and Venous Oxylipins Reveals Obesity-Associated Metabolic Signatures in HFpEF

Heart failure with preserved ejection fraction (HFpEF) makes up about half of all heart failure cases, and obesity is now seen as a major factor driving it. Oxylipins are fat-derived signaling molecules that have been linked to worse outcomes in HFpEF, but it is still not clear how they are connected to obesity. To evaluate the association between obesity and arterialized and venous oxylipins in HFpEF patients, researchers conducted a single-center cohort study where 90 patients with HFpEF underwent transthoracic echocardiography and right heart catheterization with arterialized pulmonary capillary and venous blood sampling. Serum oxylipins were quantified via liquid chromatography-mass spectrometry (LC-MS). A paper based on this research was published in the journal Metabolomics.¹

How Does Obesity Contribute to the Development and Worsening of HFpEF?

HFpEF, which makes up nearly half of all heart failure cases and is becoming more common as populations age and rates of obesity and related metabolic conditions continue to rise, is a complex condition that involves how the heart, blood vessels, kidneys, and metabolism all interact with each other.^2-4

Obesity is very common in HFpEF and is now increasingly seen as a contributing cause rather than just a condition that happens alongside it.⁵ Fat tissue is not just storage—it actively acts like a hormone-producing organ, releasing signaling substances such as adipokines, inflammatory molecules, and lipid messengers. These can contribute to widespread inflammation in the body and can also lead to scarring of the heart muscle, problems with blood vessel function, and reduced ability of the heart to relax properly.⁶ Obesity is also linked to the body holding on to more salt and water, which increases blood volume and raises the pressure the heart must work against when it fills.⁷ Changes in the lung blood vessels related to obesity can lead to higher blood pressure in the lungs and problems with the right side of the heart. These are major reasons why people with HFpEF often have difficulty exercising and are more likely to experience worse outcomes.⁸

What Metabolic and Cardiovascular Differences Are Seen in Obese versus Non-Obese HFpEF Patients?

Out of the 90 patients participating in the study, 61 (about 68%) were classified as obese. Compared with non-obese patients, those with obesity tended to be younger, more often female and African American, and had higher rates of diabetes (54.1% vs. 17.2%). They also showed thicker heart muscle walls in certain regions of the heart. Statistical analyses showed that obesity was linked to lower levels of several oxygenated fat-related molecules in the blood, including 12,13-DiHOME, 19,20-DiHDoPE, 11,12-DiHETrE, 9,10-DiHOME, and 5(S),6(S)-DiHETE. On the other hand, one molecule—19R-hydroxy-prostaglandin E1—was found at higher levels in people with obesity. In blood taken from veins, higher levels of 15(R)-PGE1 and 19R-hydroxy-prostaglandin E1 were also associated with obesity. Finally, obese patients were more likely to fall into a more severe subtype of pulmonary hypertension involving both pre- and post-capillary disease.¹

“Obesity in HFpEF,” wrote the authors of the paper,¹ “is associated with reduced oxylipin diol levels, higher levels of prostaglandin E1 metabolites, and higher burden of pulmonary hypertension.”

The researchers emphasized that their results show links rather than cause-and-effect relationships. The connections they observed between obesity, worsening pulmonary hypertension, and oxylipin patterns may be driven by broader underlying heart and metabolic changes rather than one directly causing the other. They suggest that future studies combining detailed heart pressure measurements with oxylipin testing will be needed to find out whether specific oxylipin patterns can help predict disease progression.¹

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References

1. Yadav, A.; Manandhar, S.; Kloster, A. et al. Obesity is Associated with Distinct Oxylipins in Heart Failure with Preserved Ejection Fraction. Metabolomics 2026, 22 (3), 69. DOI: 10.1007/s11306-026-02449-x
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7. Pandey, A.; Patel, K. V.; Vaduganathan, M. et al. Physical Activity, Fitness, and Obesity in Heart Failure with Preserved Ejection Fraction. JACC Heart Fail. 2018, 6 (12), 975-982. DOI: 10.1016/j.jchf.2018.09.006
8. Obokata, M.; Reddy, Y. N. V.; Pislaru, S. V. et al. Evidence Supporting the Existence of a Distinct Obese Phenotype of Heart Failure with Preserved Ejection Fraction. Circulation 2017, 136 (1), 6-19. DOI: 10.1161/CIRCULATIONAHA.116.026807