# A Small Contribution to a Large Problem: Leptin-Signaling and the Gut-Brain Axis

> **NIH NIH P20** · UNIVERSITY OF HAWAII AT MANOA · 2024 · $181,874

## Abstract

PROJECT SUMMARY - A small contribution to a large problem: Leptin-signaling and the gut-brain axis
The proposed research aims to solve the self-assembly of the leptin receptor (LEP-R) complex controlling energy
homeostasis and its influence on gut microbiota composition. Leptin and its receptor have been proposed to be
the link between nutritional status and the gut microbiome, although whether this hormone and its action is
Despite its important role in human health, the
molecular details of the human leptin receptor (hLEP-R) complex remain elusive. Our interdisciplinary
approach utilizing a combination of molecular dynamic (MD) simulations, in vitro biophysical characterization,
in cell assays, and in vivo experiments using Drosophila melanogaster (D. melanogaster) as our genetic model
system puts our research in a unique position to build on our previous discoveries in human leptin (hLEP).
Thus,
conserved across the animal kingdom is poorly studied.
taking advantage of the background developed in mammalian research to study the phenotype of D.
melanogaster to test our hypothesis if LEP-signaling is a shared character among animals. The aim for year
one is to produce transgenic flies, solve the backbone assignments, and find experimental conditions for Cryo-
EM experiments for the LEP-R complexes using transfer electron microscopy (TEM) at the MICRO core at UH.
The long-term aim is to understand LEP-signaling and the role of the diet and microbiome in driving the signaling
behavior. We will define the signaling-complex's molecular details, effects of the gut microbiota’s secreted
enzymes on this complex, and, reciprocally, leptin’s impact on microbiome composition. In this project, we will
characterize human LEP (hLEP) and hLEP-R’s, elucidating the molecular details of LEP-signaling to set the
stage for studies of the links among diet, microbiota, and LEP-R.

## Key facts

- **NIH application ID:** 10890821
- **Project number:** 5P20GM125508-07
- **Recipient organization:** UNIVERSITY OF HAWAII AT MANOA
- **Principal Investigator:** Ellinor Haglund
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $181,874
- **Award type:** 5
- **Project period:** 2018-08-15 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10890821

## Citation

> US National Institutes of Health, RePORTER application 10890821, A Small Contribution to a Large Problem: Leptin-Signaling and the Gut-Brain Axis (5P20GM125508-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10890821. Licensed CC0.

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