Effects of Obesity and Intensity of Exercise on Ghrelin Levels

NCT ID: NCT04581980

Last Updated: 2025-09-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-14
• Study Completion Date: 2025-04-16

Brief Summary

This study is investigating the effect of different intensities of exercise on levels of the hormone, ghrelin. In addition, we will be examining the relationship between any exercise induced changes in ghrelin and insulin sensitivity, obesity, and vascular function.

Detailed Description

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 techniques on ghrelin release.

Conditions

Obesity; Insulin Resistance; Cardiovascular Risk Factor

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: HEALTH_SERVICES_RESEARCH
• Blinding Strategy: NONE

Study Groups

Control

This arm will receive no exercise

Group Type: NO_INTERVENTION

No interventions assigned to this group

Moderate Intensity Exercise

This group will exercise on a cycle ergometer (Lode Bike) at moderate intensity. Moderate intensity will be defined by the lactate threshold. A heart rate monitor will be utilized at all times to record heart rate.

Group Type: EXPERIMENTAL

Exercise

Intervention Type: OTHER

Participants will exercise on a cycle ergometer

High Intensity Exercise

This group will exercise on a cycle ergometer (Lode Bike) at high intensity. High intensity will be defined by an by 75% of the difference between the lactate threshold and peak.

Group Type: EXPERIMENTAL

Exercise

Intervention Type: OTHER

Participants will exercise on a cycle ergometer

Interventions

Exercise

Participants will exercise on a cycle ergometer

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 18-55 years of age
• BMI between 18-40 kg/m2
• Untrained (reports less than 2 days/week of exercise)
• Weight stable (no significant loss/gain of more than 3kg in the past 3 months)
• Females must be premenopausal and report normal menstrual cycles

Exclusion Criteria

• History of diabetes, gastrointestinal disease, or endocrine disorder
• Smoking (must have quit at least 6 months prior)
• Disordered eating
• Females currently pregnant or undergoing fertility treatments
• The following medications (due to their effect on insulin sensitivity ,endothelial function and/or ghrelin secretion): Synthetic growth hormone, metformin, synthetic insulin, sulfonylureas, meglitinides, Thiazolidinediones, DPP-4 inhibitors, GLP-1 receptor agonists, SGLT2 inhibitors , biguanides, alpha-glucosidase inhibitors, phosphodiesterase inhibitors, beta-blockers, alpha-blockers, ACE-inhibitors, ARB's, fibrates, glucocorticoids, olanzapine

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

University of Virginia

OTHER

Sponsor Role: lead

Responsible Party

Arthur L Weltman

Dr. Arthur Weltman, Professor of Kinesiology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of Virginia

Charlottesville, Virginia, United States

Countries

United States

Other Identifiers

5R01DK129510-02

Identifier Type: NIH

Identifier Source: secondary_id

View Link

200241

Identifier Type: -

Identifier Source: org_study_id