# The mechanistic study on irisin-mediated immune response and its role in adipose tissue dynamics

> **NIH DK K01** · DANA-FARBER CANCER INST · 2026 · $150,722

## Abstract

PROJECT SUMMARY
Obesity and its associated type II diabetes have reached worldwide epidemic. Exercise training is a robust means
to increase energy expenditure and downregulate chronic inflammation, and serves as an excellent primary
intervention to combat obesity and associated metabolic disorders. Exercise mediates an increase in the
circulating levels of certain hormones released from muscle that mediate certain exercise-induced adaptations
of the body. Irisin is the first polypeptide molecule identified from the exercised muscle: irisin stimulates several
adaptations, including the “beiging” of white adipose tissue, bone remodeling, and improvement of cognition and
motor function in Alzheimer’s and Parkinson’s diseases. In collaboration with the Diane Mathis lab, we identified
a specific immune pathway—the IL33-ST2 pathway— that is regulated by irisin to modulate adipose
inflammation, in inguinal fat tissue (iWAT) and also in visceral fat tissue (eWAT). The molecular basis of irisin
actions has been elaborated in my recent published work: (1) irisin collaborates with Hsp90α, another
extracellular proteinthat activates integrin structure to allow high-affinity binding; (2) Hsp90α itself is induced with
exercise in mice; (3) irisin binds to a face that is distinct from the docking sites of the classical integrin ligands,
implying that this surface can be targeted by agonists without interfering with canonical integrin functions. My
current research plan is devised to (i) test our molecular mechanistic model in the context of adipose-immune
cross talk (Aim 1); (ii) further dissect the downstream immune response pathways that respond to irisin action
(Aim 2), (iii) understand how the irisin-mediated immune pathway regulates different thermogenic programs
(Aim 2), and (iv) identify other “irisin-style” hormone molecules that serve a protective role in metabolic diseases
such as diabetes (Aim 3), a discovery-based study planned to pave the road to my first R01. Collec

## Key facts

- **NIH application ID:** 11241160
- **Project number:** 5K01DK141969-02
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** Mu  A
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** DK
- **Fiscal year:** 2026
- **Award amount:** $150,722
- **Award type:** 5
- **Project period:** 2025-01-01T00:00:00 → 2027-11-30T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11241160

## Citation

> US National Institutes of Health, RePORTER application 11241160, The mechanistic study on irisin-mediated immune response and its role in adipose tissue dynamics (5K01DK141969-02). Retrieved via AI Analytics 2026-07-12 from https://api.ai-analytics.org/grant/nih/11241160. Licensed CC0.

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