# Project 4: Brown Adipocyte Physiology: Role of Selenium Recycling

> **NIH NIH P20** · UNIVERSITY OF HAWAII AT MANOA · 2022 · $305,432

## Abstract

PROJECT SUMMARY
Humans and rodents have constitutive brown adipose tissue (BAT), a tissue that responds to fatty acid overload
by dissipating heat, an adaptive mechanism called diet-induced thermogenesis (DIT). DIT contributes to energy
homeostasis and restricts obesity development. Activation of DIT by fat overload depends on thyroid hormones
and is induced by glutathione (GSH) depletion via increases in reactive oxygen species (ROS). Two
selenoproteins, iodothyronine deiodinase 2 (Dio2) and GSH peroxidase 1 (Gpx1), are involved in the regulation
of adaptive thermogenesis. Selenoproteins have in their primary structure the micronutrient selenium (Se)
incorporated as the amino acid selenocysteine (Sec). Sec is decomposed by the enzyme Sec lyase (Scly) into
selenide, used for de novo synthesis of Sec, triggering a Se recycling process required to maintain optimal levels
of selenoproteins, particularly when Se is limiting. Se recycling is key for energy balance, as disruption of the
Scly gene in mice (Scly KO) leads to weight gain worsened by Se deficiency. It is unknown if Se recycling
modulates BAT Se levels, impacting Dio2 and Gpx1 activities, ultimately contributing to DIT activation. While
most investigations into the role that selenoproteins play in obesity and metabolism have focused on dietary Se
intake, this project will employ innovative models that couple the understudied mechanisms of Se recycling along
with Se intake. Our long-term research goal is to determine how molecular mechanisms regulated by bioavailable
Se contribute to obesity development, enabling tailored nutritional strategies for improving human health status
via modulation of micronutrient intake. The overall objective of this proposal is to determine how Se intake and
Se recycling modulate brown adipocyte physiology and activation of DIT. In Aim 1, we will determine the role of
Se recycling in BAT activation in obesity. In Aim 2, we will determine if Se supplementation rescues brown
adipocyte DIT response after the loss of Scly. In Aim 3 we will determine how Scly controls selenoprotein
degradation in palmitate-treated brown adipocytes. These results will clarify the modulatory effect of Se on brown
adipocyte physiology. By including both Se intake and recycling, this innovative project will provide significant
new insights into the role that Se plays in brown adipocyte physiology in the pathological context of obesity.

## Key facts

- **NIH application ID:** 10335723
- **Project number:** 1P20GM139753-01A1
- **Recipient organization:** UNIVERSITY OF HAWAII AT MANOA
- **Principal Investigator:** Lucia Andreia Seale
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $305,432
- **Award type:** 1
- **Project period:** 2022-03-20 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10335723

## Citation

> US National Institutes of Health, RePORTER application 10335723, Project 4: Brown Adipocyte Physiology: Role of Selenium Recycling (1P20GM139753-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10335723. Licensed CC0.

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