Diet-Induced Changes in GEnetic Material (DIG 'EM)

A Pilot Study to Examine Metabolic Flexibility as a Mechanism for Diet- Induced Epigenetic Alterations in Male Gametes

This is a pilot study in 10 men to test the hypothesis that perturbations in substrate flux and the circulating metabolic and pro-inflammatory milieus during a high-fat diet paradigm will modulate DNA methylation of genes in sperm associated with obesity and cardiometabolic dysfunction.

Study Overview

• Status: Recruiting
• Conditions: Body Weight; Diet, Healthy; Metabolic Disturbance

Detailed Description

The Paternal Origins of Health and Disease (POHaD) hypothesis was introduced to emphasize the need for research on paternal transmission of environmental exposures on offspring disease development. Paternal exposure to an obesogenic diet has been shown to imprint epigenetic predisposition to metabolic diseases which can be evident in offspring for up to 5 generations. In support, observational studies in men show that high-fat diets and diets high in processed foods significantly reduced the quantity and quality of sperm, including motility, morphology, and concentration, and DNA methylation of genes associated with obesity and cardiometabolic dysfunction. Yet, there are no experimental diet manipulation studies in males to understand the contribution of an acute obesogenic diet (i.e., high-fat) on DNA methylation of genes associated with obesity and cardiometabolic diseases in male gametes.

The research aims of this study are to: 1) measure DNA methylation of genes in semen in response to a healthy and high-fat diet, 2) examine metabolic flexibility in response to a healthy and high fat diet and its contribution to DNA methylation in semen, and 3) examine the metabolic and inflammatory milieu in response to a healthy and high fat diet and its contribution to DNA methylation in semen. To achieve these aims, we will conduct a cross-sectional, observational study in 10 healthy male participants 20-35 years of age using two diets (Healthy Diet: 27% Fat, 55% Carbohydrate, 15% Protein followed by a High-Fat Diet: 50% Fat, 35% Carbohydrate, 15% Protein).

• Study Type: Observational
• Enrollment (Estimated): 10

Contacts and Locations

• Study Contact: Name: Emily Flanagan, PhD; Phone Number: (225) 763-2828; Email: Emily.Flanagan@pbrc.edu

Study Locations

• United States
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Recruiting
      • Pennington Biomedical Research Center
      • Contact: Emily Flanagan, PhD; Phone Number: 225-763-2828; Email: Emily.Flanagan@pbrc.edu
      • Principal Investigator: Emily Flanagan, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

This study will enroll healthy men from the greater Baton Rouge area who meet the above eligibility criteria and are willing to participate in this research trial.

Description

Inclusion Criteria:

• Male based on biological sex
• Age 20-35 years
• BMI between 18.5 and 24.9 kg/m2
• White/Caucasian
• Willing to consume pre-prepared meals
• Willing to wear an accelerometer and continuous glucose monitor (CGM)
• Willing to track diet intake
• Willing to stay 24 hours, including overnight in a research clinic
• Willing to provide blood and sperm samples
• Willing to consent to whole-genome sequencing of DNA

Exclusion Criteria:

• Unstable weight in the last 3 months (±5% weight loss or gain)
• Shift work or working in a factory setting
• Habitual smoking or use of tobacco products, including vaping, within the past 6 months.
• History of clinically diagnosed diabetes
• Hypertension (>140/90 mmHg measured at screening)
• Has undergone bariatric surgery
• History of cardiovascular disease, neurological disease, or other chronic diseases, including cancer
• History of human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)
• Adherence to special or restrained diets (e.g., low-CHO, low-fat, or vegetarian/vegan diets) or food allergies associated with study foods.
• Currently engaging in >150 minutes moderate-intensity or >75 minutes of vigorous-intensity physical activity each week
• Drinking more than 14 servings of beer or alcohol per week
• Depressive (Score ≥10), anxiety (Score ≥8), and stress (Score≥15) symptomology (Score ≥16) from the 42-item Depression, Anxiety, Stress Scales (DASS)

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sperm DNA methylation	Incidence of DNA methylation (whole genome/epigenome wide) of genes in sperm measured using bisulphate sequencing	Baseline, Immediately after the healthy diet, Immediately after the high-fat diet

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sperm DNA Damage	Comet Assay to determine DNA fragmentation in sperm.	Baseline, Immediately after the healthy diet, Immediately after the high-fat diet

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metabolic Flexibility (indirect)	Change in respiratory quotient (RQ) from a fasted to a fed state using a metabolic chamber.	Immediately after the healthy diet, Immediately after the high-fat diet
Metabolic Flexibility (direct)	Changes to circulating glucose from a fasted (0 minutes) to a fed state (240 minutes).	Immediately after the healthy diet, Immediately after the high-fat diet
Continuous glucose monitoring	Mean Amplitude of Glycemic Excursions (MAGE) in response to healthy and high fat diets.	Immediately after the healthy diet, Immediately after the high-fat diet
Insulin sensitivity	Mean 24hr glucose and total 24hr c-peptide excretion	Immediately after the healthy diet, Immediately after the high-fat diet

Collaborators and Investigators

• Sponsor: Pennington Biomedical Research Center

Publications and helpful links

Helpful Links

• Official Study Landing Page

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2023
• Primary Completion (Estimated): October 3, 2024
• Study Completion (Estimated): October 3, 2024

Study Registration Dates

• First Submitted: January 4, 2024
• First Submitted That Met QC Criteria: February 1, 2024
• First Posted (Actual): February 12, 2024

Study Record Updates

• Last Update Posted (Actual): February 12, 2024
• Last Update Submitted That Met QC Criteria: February 1, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: DNA Damage; Preconception; Metabolic Flexibility; Healthy Weight; High-Fat Diet; Sperm DNA Methylation; Substrate Flux
• Additional Relevant MeSH Terms: Body Weight
• Other Study ID Numbers: PBRC 2023-043

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No