# Modulation of Ghrelin Release by Exercise Intensity: The Role of Obesity and Prediabetes Status

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2021 · $323,000

## Abstract

Project Summary
 The goal of this proposal is to characterize the effects of two exercise “intensity doses” on total ghrelin, acyl
ghrelin, and des-acyl ghrelin in lean and obese adults with and without prediabetes. Ghrelin (TG) is involved in
the regulation of appetite, energy balance, glucose metabolism and insulin sensitivity. Ghrelin exists in the blood
in a des-acyl form (DAG ~78% of TG), and in an acylated form (AG ~22% of TG). Despite being less abundant,
AG is has multiple actions that promote energy storage, including stimulation of appetite, inhibition of insulin
release from the pancreas, and increases in adiposity via a widely characterized growth hormone secretagogue
receptor. Conversely, DAG often opposes AG promoting negative energy balance (appetite suppression and
reduced fat mass (FM)) and improving insulin sensitivity, acting through a receptor not yet identified. The optimal
ratios of TG, DAG, and AG are not clear. Likewise, there is a need for targeted approaches that can effectively
manipulate these peptides to aid in the prevention and/or treatment of obesity, metabolic syndrome, prediabetes
and type 2 diabetes. Exercise provides a unique therapeutic approach in the treatment of dysregulated ghrelin.
Limited animal and human studies examining exercise and ghrelin release are mostly equivocal or only
document TG and/or a single (e.g. AG) form of ghrelin. As DAG and AG can act synergistically,
antagonistically, or have independent effects, the quantification of these peptides in response to exercise is
critical to understanding the role of exercise on ghrelin release and ghrelin's exercise induced influence on
overall glucose regulation and energy balance. Exercise intensity may be key, as exercise that elevates
levels of lactate suppress AG and appetite post exercise. Here we propose to address this gap in knowledge
by defining the role of acute exercise intensity, at doses above and below the lactate threshold, on TG, AG,
and DAG release in lean and obese individuals with and without prediabetes. Specific Aim 1: Examine
effects of exercise intensity on ghrelin, insulin, glucose and self-reported appetite. Hypothesis: Higher
exercise intensity will result in differential effects on TG, AG, DAG, AG/DAG, insulin, and glucose AUC's, and
appetite; affected by sex, obesity, abdominal visceral fat (AVF), and prediabetes status. Specific Aim 2:
This is an exploratory aim using regression modeling to examine exercise-induced changes in
ghrelin on glucose, insulin and appetite. Hypothesis: TG, AG, DAG and AG/DAG alterations will
differentially predict changes in glucose metabolism, insulin sensitivity, and appetite. These alterations vary
by sex, levels of obesity, AVF, and prediabetes. Results from this pilot/feasibility application will inform
a larger submission that defines therapeutic exercise targets for TG, AG, and DAG, and examines the
effects of individualized exercise training using precision exercise prescription technique...

## Key facts

- **NIH application ID:** 10279846
- **Project number:** 1R01DK129510-01
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Arthur Weltman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $323,000
- **Award type:** 1
- **Project period:** 2021-07-05 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10279846

## Citation

> US National Institutes of Health, RePORTER application 10279846, Modulation of Ghrelin Release by Exercise Intensity: The Role of Obesity and Prediabetes Status (1R01DK129510-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10279846. Licensed CC0.

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