# MICRORNA REGULATION OF ADIPOSE TISSUE IMMUNE RESPONSE IN OBESITY

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2024 · $677,629

## Abstract

Project Summary
Obesity cultivates complex immune responses in white adipose tissue (WAT), which may contribute to the
development of insulin resistance and type 2 diabetes mellitus (T2DM). However, there still exists a gap in
knowledge on cellular mechanisms regulating “obesity-specific” immune responses that precludes the
development of novel immune therapies to treat obesity and related insulin resistance and T2DM. We were one
of the first to report T cells in WAT in obesity. Further studies from us and others showed that WAT conventional
T cells promote, and regulatory T cells (Tregs) protect against, insulin resistance in obesity. Nonetheless, the
mechanisms underlying WAT Treg homeostasis and mediating their metabolic benefits remain incompletely
understood. This application aims to investigate microRNA-30a (miR-30a) regulation of WAT Tregs and its
impacts on WAT immune response and metabolism in obesity. This proposal builds on our novel pilot data: 1)
miR-30a expression in WAT correlated positively with insulin sensitivity in obese mice and people; 2) enforced
miR-30a expression in WAT promoted whole-body insulin sensitivity in obese mice; 3) miR-30a levels were high
in WAT Tregs in lean but reduced in obese mice; 4) enforced miR-30a expression in WAT of obese mice
increased WAT Treg numbers; 5) specific overexpression of miR-30a in Tregs increased WAT Treg numbers
and improved insulin sensitivity in mice fed high-fat diet. Therefore, we hypothesize that miR-30a in WAT
stimulates expansion of WAT Tregs and improves Treg functions to increase insulin sensitivity. We will
test this hypothesis by pursuing three aims: Aim 1 will define effects of cell (Treg vs adipocyte)-restricted miR-
30a on WAT immune response and metabolism in obesity and establish cell-specific roles of miR-30a; Aim 2
will build on our additional pilot data that miR-30a delivery in WAT suppresses STAT1 (a key inflammatory
transcription factor) and establish how miR-30a targeting of Stat1 governs WAT Treg homeostasis in obesity;
Aim 3 will build on our novel data that compared to diet high in saturated fat, diet high in unsaturated fat induces
higher levels of WAT miR-30a and Tregs in mice and examine dietary regulation of miR-30a and its role in WAT
immune response and metabolism. We will accomplish these aims using gain-of-function and loss-of-function
approaches in genetically modified animal models, cutting-edge immunophenotyping and transcriptomics, gold
standard clamp for insulin sensitivity, and other state-of-the-art tools. Upon completing these aims, we expect to
have uncovered a novel mechanism that may help develop new therapies that leverage the immune system to
treat obesity and T2DM.

## Key facts

- **NIH application ID:** 11073686
- **Project number:** 1R01DK139397-01A1
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Sean Hartig
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $677,629
- **Award type:** 1
- **Project period:** 2024-09-18 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11073686

## Citation

> US National Institutes of Health, RePORTER application 11073686, MICRORNA REGULATION OF ADIPOSE TISSUE IMMUNE RESPONSE IN OBESITY (1R01DK139397-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11073686. Licensed CC0.

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