# Adipose T cell microRNAs (miRs) regulate macrophage function during obesity

> **NIH NIH R01** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 2021 · $380,000

## Abstract

ABSTRACT
Over the past 20 years, the prevalence of obesity in the United States and worldwide has reached epidemic
proportions. Obesity is a very powerful health determinant that facilitates the development and progression of
several metabolic diseases, insulin resistance and chronic inflammation. High fat diet (HFD) consumption
positively correlates with development of obesity. T cells infiltrate adipose tissue during the early development
of obesity (prior to macrophage influx) and are strongly implicated in the initiation of inflammation associated
with obesity. In both humans and mice, macrophage abundance increases in obese adipose tissue and can
develop either M1 (pro-inflammatory) or M2 (anti-inflammatory) phenotypes. During obesity progression
differential expression of microRNAs (miRs) by naive and activated T cells suggests their importance in T cell
effector (Teff) functions. Further, it is well established that miRs extensively regulate adipocyte development and
function. We noticed T cell homeostatic expansion and changes in macrophage abundance and phenotype in
adipose tissue of HFD fed mice compared to those fed a normal diet (ND). Specifically, our preliminary data
indicates that HFD downregulates adipose resident T cell miRs-10a, -125b and -1247 and mimics miRs' in-vivo
reversal of the expression of metabolic markers associated with obesity and modulates macrophage abundance.
Based on strong rigor and preliminary data, our central hypothesis is that T cell miRs-10a, -125b and 1247 are
essential for regulating crosstalk between adipocytes, T cells and macrophages during diet-induced
obesity. To support this premise, we will test whether adipose T cell miRs play a crucial role in diet-induced
obesity (DIO) (Aim 1); identify the mechanisms by which T cell miRs are downregulated in DIO (Aim 2); determine
whether adipose T cell miRs mediate macrophage function in DIO (Aim 3). For the first time, we will explore
how resident adipose tissue-derived T cell miRs alter metabolic function and obesity. Testing this hypothesis will
provide an enhanced understanding on interactions between T cell miRs, T cell expansion, and macrophage
and adipocyte function in the adipose tissue microenvironment that may allow for effective prevention and
treatment options for obesity and metabolic dysfunction.

## Key facts

- **NIH application ID:** 10240751
- **Project number:** 5R01AI140405-03
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **Principal Investigator:** Udai P. Singh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $380,000
- **Award type:** 5
- **Project period:** 2020-02-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10240751

## Citation

> US National Institutes of Health, RePORTER application 10240751, Adipose T cell microRNAs (miRs) regulate macrophage function during obesity (5R01AI140405-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10240751. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*