# Leptin Promotes Allergic Asthma through Unfolded Protein Responses

> **NIH NIH R21** · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · 2020 · $227,250

## Abstract

Project Summary
Allergic asthma and obesity are amongst the leading health problems in the world. Recent Meta-
analysis studies implicated a positive relationship between serum leptin, an adipokine elevated in
obese individuals, and the risk of asthma. However, it is not well understood how obesity-
associated elevation of leptin increases the risk of asthma, representing a critical knowledge gap.
This proposal will close an aspect of this gap, by exploring how leptin controls pro-allergic
lymphocyte responses through targeting the endoplasmic reticulum (ER) stress-unfolded protein
response (UPR) pathway and contributes to allergic reactions. Fully understanding the role of
leptin in control of allergic inflammation may suggest novel methods for treatment of allergic
airway disease. Our immediate objective is to determine how leptin regulates the development
and function of pro-allergic lymphocytes and controls allergic inflammation. Given the UPR
pathway play an essential role in secretory cell function (Scientific Premise), we formulate a novel
hypothesis that leptin may activate the UPR pathway that promotes pro-allergic lymphocyte
responses and exacerbates allergic airway inflammation. Specific Aims: Aim 1. Determine the role
of leptin-XBP1 axis in allergic lymphocyte responses; Aim 2. Delineate the molecular mechanism
whereby leptin induces the expression of ER stress-UPR factors and confirm the UPR-dependent
function of leptin in allergic reactions in vivo. This project is significant since it will bridge obesity
and the development of allergic asthma by the pathogenic role of leptin-mediated ER-stress-UPR.
This project might lead to new options for the development of therapeutic approaches. The
proposed research is innovative because we will investigate a previously unknown regulatory
pathway in pro-allergic lymphocytes, by which leptin promotes allergic reactions.

## Key facts

- **NIH application ID:** 9868887
- **Project number:** 5R21AI142200-02
- **Recipient organization:** UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
- **Principal Investigator:** Xuexian Yang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $227,250
- **Award type:** 5
- **Project period:** 2019-02-11 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9868887

## Citation

> US National Institutes of Health, RePORTER application 9868887, Leptin Promotes Allergic Asthma through Unfolded Protein Responses (5R21AI142200-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9868887. Licensed CC0.

---

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