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.

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).

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)

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.