Environmental health sciences postdoctoral researcher Karilyn Sant recently received a three-year, $183,234 Ruth L. Kirschstein Postdoctoral Individual National Research Service Award from the National Institute of Environmental Health Sciences to examine the mechanisms by which environmental exposures during embryonic development may lead to an increased risk for diabetes and metabolic dysfunction.
The Kirschstein-NRSA postdoctoral fellowship is intended to enhance the research training of promising postdoctoral candidates who have the potential to become productive, independent investigators in scientific health-related research fields relevant to the missions of the participating NIH Institutes and Centers.
“This award not only provides funds to support my current research, but has a positive impact on my scientific career,” says Sant, who works under the supervision of assistant professor Alicia Timme-Laragy. “It really builds upon the hard work that Dr. Timme-Laragy and I have been conducting and sharing over the past couple of years.”
“This is a fantastic award for Kari,” adds Timme-Laragy. “It provides protected time to devote to this research, and it also is an important step towards establishing her career. She is a dedicated scientist who thoroughly researches the theoretical and feasibility aspects of her proposed studies, while grounding the laboratory experiments in clear translational health outcomes.”
Sant’s study aims to identify the mechanisms by which environmental exposures during embryonic development may influence embryonic nutrition, and the long-term consequences which predispose individuals to metabolic syndrome later in life.
One of the best characterized pathways implicated in metabolic dysfunction is the activation of the peroxisome proliferator-activated receptor (PPAR) signaling pathway, which guides cellular processes and nutrient utilization. The PPAR signaling pathway is an important sensor for processes governing energy metabolism and adipogenesis, and therefore has broad implications for obesity and diabetes research.
“These pathways act as nutrient-sensors, telling cells to store nutrients when they are ample or conserve resources when they are scarce,” says Sant. “Common environmental toxicants can stimulate these pathways, confusing the body’s metabolism.”
Preliminary data demonstrates that embryonic exposure to perfluorooctanesulfonic acid (PFOS), a PPAR-activating toxicant, alters pancreas morphology and embryonic expression of hormones such as insulin and digestive enzymes crucial for metabolism. Epidemiological studies have associated developmental exposures to PFOS with low birthweight, yet these same exposures are associated with obesity and diabetes later in life. This work will explore this disparity, seeking to identify key windows of development during which these metabolic programming events take place.
“This research could help us to better understand the processes governing embryonic nutrition, of which very little is known, and will explore how environmental toxicants modulate these processes differently throughout the life course,” notes Sant.
Sant will use the zebrafish embryo—a homologous model for human embryonic development and nutrition—in an attempt to discover windows of susceptibility during which chronic PPAR activation can influence pancreatic function and can increase risk for obesity and diabetes.
“For decades, scientists have provided evidence supporting the ‘thrifty phenotype hypothesis’—that reduced fetal growth is often associated with chronic diseases such as obesity later in life,” adds Sant.
“Here, we are exploring how the embryo ‘perceives’ the nutritional environment during toxic exposures, and how that influences metabolism following development. By uncovering the mechanisms governing these adaptive processes, we hope to shine light on the embryonic window of development as an important mediator of energy metabolism throughout the life course. Ultimately, we hope this research will inform obesity and diabetes prevention programs targeted toward pregnant women and young children.”