# Effect of TRB3 and Leucine Supplement on Beige Fat Formation

> **NIH NIH R16** · TENNESSEE STATE UNIVERSITY · 2024 · $142,000

## Abstract

Obesity is an alarming signal for the risk of Type 2 diabetes, cardiovascular disease, and metabolic diseases in
humans. Obesity results from an energy imbalance, and therefore stimulating adaptive thermogenesis has
been proposed to prevent and/or treat obesity and Type 2 diabetes. Although the identification of heat-
producing white adipocytes, beige fat, has drawn considerable attention, and this type of fat is thought to
increase energy expenditure, the mechanism and signaling molecules involved in the development of beige fat
have not yet been fully understood. Furthermore, effective medication or dietary supplement are not currently
available. Our goal is to identify novel molecule(s) that regulates beige fat formation and activity. We
hypothesize in this study that Leucine supplement improves beige fat formation by suppressing TRB3, and that
transplantation of beige fat from Leucine fed mice prevents mice from high fat diet-induced obesity and
diabetes. This hypothesis has been formulated on the basis of our preliminary data showing that knockout of
TRB3 promotes beige fat formation. Furthermore, Leucine, a branched-chain amino acid effectively
suppresses TRB3 expression in adipose tissue. We will test the hypothesis by pursing three specific aims. In
Aim 1, we will determine the mechanism(s) by which Leucine promotes beige fat formation. In Aim 2, we will
determine if Leucine supplement augments exercise training- and cold exposure-induced beige fat formation.
We expect that Leucine decreases TRB3 expression, which in turn promotes beige fat formation. Leucine
decreases TRB3 expression by suppressing ER stress. In Aim 3, we will determine if transplantation of beige
fat from Leucine fed mice protects against high fat diet-induced weight gain and insulin resistance. We
anticipate Leucine fed mice will resist high fat diet-induced weight gain and insulin resistance and promotes
beige fat formation. Transplantation of beige fat from Leucine fed mice will improve whole-body metabolism.
The proposed research will establish the function of TRB3 and Leucine in the beige fat formation and identify a
new approach for treating obesity and metabolic diseases. The study will be innovative in 1) investigating the
underlying mechanism by which Leucine promotes beige fat formation and metabolism; 2) studying the role of
TRB3 and Leucine in beige fat, which has not yet been studied; 3) utilizing beige fat transplantation technique
to assess the tissue effect on whole body metabolism; and 4) attempting to identify TRB3 inhibition- and/or
Leucine supplement-induced adipokines from beige fat improving whole body glucose metabolism. The
proposed study will be also significant in providing new insights into the development of treatment strategies
for obesity and Type 2 diabetes. The study will provide an opportunity for African America and/or
underrepresented students to be trained as independent researchers.

## Key facts

- **NIH application ID:** 10850271
- **Project number:** 1R16GM149457-01A1
- **Recipient organization:** TENNESSEE STATE UNIVERSITY
- **Principal Investigator:** Ho-Jin Koh
- **Activity code:** R16 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $142,000
- **Award type:** 1
- **Project period:** 2024-07-19 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10850271

## Citation

> US National Institutes of Health, RePORTER application 10850271, Effect of TRB3 and Leucine Supplement on Beige Fat Formation (1R16GM149457-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10850271. Licensed CC0.

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