# Systems-based approaches for investigating tissue communication during exercise

> **NIH NIH U01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2022 · $334,862

## Abstract

ABSTRACT
Daily physical activity is a known intervention to prevent or ameliorate complications associated with
metabolic-related diseases. However, the mechanisms underlying metabolic adaptations to chronic exercise
training remain inadequately understood. Moreover, human studies show a broad range of exercise
adaptation with some individuals refractory to specific metabolic improvements associated with training.
Since conventional animal studies have focused primarily on few rodent strains, in the current application
we will interrogate exercise training adaptations in ~100 diverse male and female strains of inbred mice
known as the UCLA Hybrid Mouse Diversity Panel (HMDP), and integrate these data with existing MoTrPAC
data repositories at the Bioinformatics Center (BIC), Stanford University. In Aim 1 we will determine the
regulatory loci controlling exercise metabolism and integrate several “omics” platforms (transcriptomics,
proteomics, metabolomics) using Bayesian analyses and Mergeomics to identify regulatory networks and
key driver nodes underlying exercise training in mice and validate these findings with publicly available data
from the MoTrPAC consortium studies of exercise training in rats and humans. In Aim 2 we will use
Quantitative Endocrine Network Interaction Estimation (QENIE) to functionally annotate novel inter-tissue
communication circuits (between cardiac and skeletal muscle, and liver, and fat) that are critical for
endurance exercise adaptation. Our findings provided herein show remarkable, sex-specific tissue crosstalk
that occurs to maintain metabolic homeostasis and in response to exercise. We will construct
communication networks between the four tissues in mouse and validate these against the plasma
proteome of human and rat (provided by the MoTrPAC consortium BIC) similar to multi-species validation
studies published previously by our group (PMCID6399495, 5935137). Moreover, we will also perform
molecular validation studies confirming exercise-stimulated changes in novel circulating factors, and
determine functionality of these communication networks using conventional loss and gain of expression
approaches. Our findings will be of strong scientific impact as we will identify novel exercise-induced
regulatory nodes and key driver pathways underlying improvements in metabolism, determine novel
exercise driven endocrine interactions, and generate a mouse sample biobank and data repository that will
be integrated into the MoTrPAC data hub for novel hypothesis generation by the entire research community.

## Key facts

- **NIH application ID:** 10438852
- **Project number:** 5U01AG070959-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Andrea L Hevener
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $334,862
- **Award type:** 5
- **Project period:** 2020-09-30 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10438852

## Citation

> US National Institutes of Health, RePORTER application 10438852, Systems-based approaches for investigating tissue communication during exercise (5U01AG070959-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10438852. Licensed CC0.

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