# Macrophage miR-130b/301b and beige adipogenesis

> **NIH NIH R01** · YALE UNIVERSITY · 2024 · $451,245

## Abstract

Project Summary
Obesityis a global health problem that increases the risk of type 2 diabetes, cardiovascular diseases,and
cancer.
As the main inducible thermogenic cell type capable of improving energy homeostasis in humans,
beige adipocytes are a potential therapeutic target to combat obesity and related comorbidities. A critical barrier
to the anti-obesity potential of beige fat is the limited understanding of the intercellular regulation of beige
adipogenesis in obesity. Adipose tissue macrophages (ATMs) have emerged as a central regulator of adipose
remodeling. Here, we have identified a microRNA cluster, miR-130b and miR-301b, as an important
macrophage-derived suppressor of adipose tissue beigeing and energy metabolism. We found that miR-130b is
upregulated in subcutaneous ATMs of both humans and mouse models with obesity. Our recent published study
showed that mice lacking miR-130b/301b globally are protected from high fat diet (HFD)-induced obesity and
glucose intolerance, concomitant with increased beigeing and decreased inflammation specifically in
subcutaneous fat depot. Further studies using myeloid-specific miR-130b/301b knockout mice showed that
deletion of miR-130b/301b specifically in myeloid cells resulted in nearly complete loss (~99%) of miR-130b in
adipose stem/stromal cells (ASCs) and in circulation, indicating that myeloid cells are the major source of miR-
130b. In vitro studies demonstrated that macrophages (Mφs) release extracellular vesicles (EVs) containing miR-
130b that are taken up by ASCs, and miR-130b overexpression in ASCs suppresses beige differentiation likely
via AMP-activated protein kinase (AMPK) and mitochondrial metabolism. However, detailed molecular
mechanism whereby miR-130b/301b, produced in myeloid cells, impacts beige adipogenesis and adipose tissue
inflammation in specific fat depots remain to be elucidated. We hypothesize that HFD increases Mφ-derived
miR-130b/301b which suppresses beige adipogenesis via EV-mediated transfer of miR-130b/301b into specific
ASCs and increases inflammation via modulation of Mφ polarization. Combining in vitro and in vivo studies using
Mφ-specific miR-130b/301b knockout mice and EV administration, our goals are to delineate cell-specific
actions of miR-130b/301b and explore therapeutic potential of EV-mediated miR-130b/301b inhibition in obesity.
Aim1 will test the hypothesis that HFD, opposed to cold, increases Mφ-derived EV uptake of miR-130b/301b
into the subtypes of adipose progenitors, impairing beige adipogenesis. Cell distribution of miR-130b/301b in
WT versus Mφ-specific miR-130b/301b KO mice will be assessed using miRNA flow cytometry and
miRNAScope. Single-cell RNAseq and Mφ/ASC co-culture will be performed. Aim2 will assess the roles of miR-
130b/30b in Mφ polarization and the underlying mechanisms. Aim3 will explore therapeutic potential of EV-
mediated miR-130b/301b inhibition in obesity and associated disorders. Results of these studies will provide
new kn...

## Key facts

- **NIH application ID:** 10853657
- **Project number:** 1R01DK138986-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Shaoning Jiang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $451,245
- **Award type:** 1
- **Project period:** 2024-04-01 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10853657

## Citation

> US National Institutes of Health, RePORTER application 10853657, Macrophage miR-130b/301b and beige adipogenesis (1R01DK138986-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10853657. Licensed CC0.

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