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

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).