Program > Browse abstracts by author > Dumargne Marie-Charlotte

Humanity is heavier than ever. In 2023, nearly half of French adults were overweight or obese. A series of European surveys recently reported that almost one in three French adults admitted being on a diet, trying to lose weight. Resistance to diet-induced weight loss may be an evolutionary legacy, whereby our ancestral bodies were programmed to ensure enough energy storage for survival in hunger times. We hypothesize that weight loss leaves an epigenetic imprint that renders weight regain easier. While the epigenetics changes associated with high fat-induced obesity have been extensively studied, the epigenome response to a weight loss is poorly described. Previous work from our group using short-read sequencing identified that, compared to lean men, spermatozoa from obese men carry a distinct epigenetic signature at genes controlling brain development and function. Profiling 5-methylcytosine mark revealed that a surgery-induced weight loss triggers an epigenetic remodeling at genes involved in the control of appetite. Reanalysis of the data suggest that some intergenic regions associated with TEs may also be modified (pilot data). Given the rapid increase in obesity prevalence across generations, we hypothesize that epigenetic remodeling at human sperm TEs participate in the acceleration of this pandemic over generations. Our preliminary results using long-read sequencing revealed a near-complete map of the human sperm Y chromosome, which controls spermatogenesis. This chromosome remained the most incomplete mapped so far because of its highly repetitive structure. Our pilot Nanopore sequencing support that we should be able to achieve an unprecedented read of DNA methylation at TEs in the human sperm epigenome. Our goal is to take advantage of this technology to demonstrate their direct implication in obesity. These hotspots may indeed represent an inherited testimony that can be transmitted to future generations to predispose their (epi)genetic make-up to easier weight gain or fat storage.