# Selenium Metabolism in the Heart: Impact of High Fructose and Low Selenium

> **NIH NIH P20** · UNIVERSITY OF HAWAII AT MANOA · 2024 · $155,398

## Abstract

This proposal will investigate the role of the selenium (Se)-recycling enzyme, selenocysteine lyase 
(Scly), in combination with high fructose and dietary Se deficiency impacts cardiac function. Se 
deficiency has been associated with an increased risk of cardiometabolic disorders including type 2 
diabetes (T2D) and atherosclerosis. A driver of cardiometabolic disorders such as T2D in humans is the 
overconsumption of fructose. High dietary fructose has been shown to induce insulin resistance, oxidative 
stress and cardiac lipid species such as triacylglycerols and diacylglycerols that are associated with 
cardiovascular diseases (CVDs), In most tissues, Se maintains redox homeostasis by controlling the 
levels of selenoproteins, such as glutathione peroxidases 1 and 4 (GPX1 and GPX4) and thioredoxin 
reductases 1 and 2 (TXNRD1 and TXNRD2), that curb reactive oxygen species (ROS), and in the case 
of GPX4, regulates ferroptosis. However, it is unknown if Scly modulates Se and selenoprotein levels in 
the heart, especially upon exposure to a high- fructose diet. In Se-dependent tissues such as the liver, 
especiallywhen Se is limiting, selenoprotein degradation may become a source of Se for selenoproteins, 
i.e. Se recycling, a reaction carried out by the enzyme selenocysteine lyase (Scly). The experiments in 
this proposal will determine how the heart metabolizes and recycles Se, impacting selenoprotein levels 
and activity, and overall heart function in Se- deficient states combined with a high fructose diet. Aim 1 
will determine if Se recycling is activated in the heart in response to a high fructose diet. Aim 2 will 
determine if Scly action reduces oxidative stress and ferroptosis in Se-deficient cardiomyocytes. The 
overall impact of this proposal is to understand how Se metabolism and recycling in the heart regulates 
local Se levels and modulates heart physiology in a high fructose environment. This will guide 
improvements on nutritional recommendations with Se supplementation or aid in the use of nanoparticle 
therapeutics to treat CVD.

## Key facts

- **NIH application ID:** 10795667
- **Project number:** 5P20GM139753-03
- **Recipient organization:** UNIVERSITY OF HAWAII AT MANOA
- **Principal Investigator:** Briana Shimada
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $155,398
- **Award type:** 5
- **Project period:** 2022-03-20 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10795667

## Citation

> US National Institutes of Health, RePORTER application 10795667, Selenium Metabolism in the Heart: Impact of High Fructose and Low Selenium (5P20GM139753-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10795667. Licensed CC0.

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