# Transcriptional Control of High-thermogenic Adipocyte Development

> **NIH NIH R01** · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · 2022 · $369,840

## Abstract

Brown adipose tissue is composed of heterogenous adipocyte populations evidenced by the coexistence
of low-thermogenic adipocytes (mitochondria content low and uncoupling protein 1 (UCP1) low) and high-
thermogenic adipocytes within the tissue, a fundamental feature of adipocyte heterogeneity and plasticity.
However, the mechanisms underlying adipocyte heterogeneity and its significance in metabolic physiology and
disease remain poorly defined. In our preliminary study, we discovered a population of JunB-enriched
adipocytes (JunB+ adipocytes) within the brown fat depot that exhibits lower thermogenic capacity and less
lipid droplets compared to high-thermogenic adipocytes. The abundance of JunB+ adipocytes is increased
during obesity. Through snRNA-seq and functional assays, we observed that inactivation of JunB in adipocytes
increased the fraction of adipocytes exhibiting high mitochondrial content and thermogenic capacity.
Importantly, JunB ablation in UCP1+ adipocytes resulted in enhanced basal and cold-induced energy
expenditure and protected mice against diet-induced obesity. Based upon these novel findings, we
hypothesize that JunB serves a critical role in governing adipocyte heterogeneity and systemic energy
and glucose homeostasis. We will elucidate the mechanisms by which JunB suppresses high-thermogenic
cell differentiation and explore the regulation of JunB+ adipocyte development by examining the identity, origin,
and fate of this distinct subpopulation. We will also use Diphtheria toxin gene A chain (DTA)-
mediated approach to ablate JunB+ adipocytes within adipose tissue to determine the physiological role of this
subpopulation in regulating energy and glucose metabolism. Characterization of JunB in regulating adipocyte
heterogeneity and plasticity will provide novel knowledge to the biology of brown adipocyte and a solid
foundation to aid in the development of therapeutic interventions for obesity and its associated disorders.

## Key facts

- **NIH application ID:** 10435752
- **Project number:** 1R01DK132643-01
- **Recipient organization:** UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
- **Principal Investigator:** Meilian Liu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $369,840
- **Award type:** 1
- **Project period:** 2022-04-20 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10435752

## Citation

> US National Institutes of Health, RePORTER application 10435752, Transcriptional Control of High-thermogenic Adipocyte Development (1R01DK132643-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10435752. Licensed CC0.

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