# Brown adipose tissue fructose metabolism

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2024 · $557,611

## Abstract

Project Summary
Chronic overconsumption of high fructose-containing food and beverages has emerged as a significant risk
factor for development of obesity, nonalcoholic fatty liver disease, and type 2 diabetes mellitus. Fructose
metabolism has been extensively investigated in the hepatocyte, where 50-70% of dietary fructose is
metabolized as well as in the small intestine and kidneys, where the fructose transporter Glut5 is highly
expressed. However, much less is known in other metabolic organs including skeletal muscle, brain and white
adipose tissue. Thus far, the impact of Glut5 and fructose metabolism in intrascapular brown adipose tissue
(iBAT) has not been investigated. While analyzing the diet/feeding-stimulated iBAT transcriptomes to gain
mechanistic insights, we observed a dramatic but transient upregulation of facilitated glucose/fructose
transporter type 5 (Glut5, [Slc2a5]) in iBAT as early as 1 h after feeding from both male and female C57BL/6J
mice but not in antibiotic-treated mice. Consistently, we also observed similar Glut5 upregulation in
differentiated human brown adipocytes after incubation with serum from fed mice. In addition, we also
observed that chronic high fructose consumption dysregulates iBAT basal Glut5 expression. This is
unexpected because Glut5 expression in white fat is fructose-independent. Our data showed for the first time
that iBAT Glut5 regulates circulating fructose homeostasis and mediates fructose-dependent iBAT whitening
and obesity. Fructose metabolism is important for glycogen and lipid accumulation in hepatocyte. Increase in
iBAT fructose metabolism due to fructose-induced Glut5 dysregulation could potentially leads to iBAT
whitening. Together with our preliminary findings that feeding-induced Glut5 expression in iBAT is eliminated in
antibiotic-treated mice, we hypothesize that high-fructose consumption promotes whitening and impairs iBAT
metabolic activity via microbiome-dependent iBAT Glut5 expression. In this proposal, we plan to delineate how
brown adipocyte Glut5 impacts iBAT metabolism. We will also determine whether high-fructose diet increase
Glut5 via microbiota-derived hyodeoxycholic acid (HDCA) to inhibit iBAT function. Finally, we will determine
liver-x-receptors (LXRs) expressed in brown adipocyte are required for whitening and metabolic activity
impairment in iBAT induced by high-fructose diet. Successful completion of this proposed study will contribute
to our understanding of high fructose diet-induced brown fat whitening and metabolic dysfunction.

## Key facts

- **NIH application ID:** 10811002
- **Project number:** 1R01DK135542-01A1
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Chong Wee Liew
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $557,611
- **Award type:** 1
- **Project period:** 2023-12-20 → 2028-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10811002

## Citation

> US National Institutes of Health, RePORTER application 10811002, Brown adipose tissue fructose metabolism (1R01DK135542-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10811002. Licensed CC0.

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