Meet the 2020 Laureates: Eleftheria Maratos-Flier, MD

Eleftheria Maratos-Flier, MD

Roy O. Greep Award for Outstanding Research

Obesity and its metabolic complications including type 2 diabetes and fatty liver disease, are among the greatest challenges to health around the world. At the heart of this problem is understanding energy balance — a complex network of interactions between the periphery and the brain. Dr. Maratos-Flier has defined two important molecular mediators of these interactions: FGF21 and melanin concentrating hormone (MCH).

In seminal work, Maratos-Flier identified the orexigenic neuropeptide MCH and showed that deletion of MCH was associated with a lean, hyper-metabolic phenotype, whereas overexpression was associated with increased susceptibility to obesity. She then defined the intracellular signaling pathways involved in MCH action, their receptors and the neural pathways upon which they act.

Maratos-Flier also has defined the role of fibroblast growth factor 21 (FGF21) in control of metabolism. She demonstrated that FGF21 expression was induced by ketogenic diet (KD) and that it served as a critical mediator of fatty acid oxidation. Thus, knockdown of FGF21 led to marked fatty liver and hypertriglyceridemia in mice eating KD. Mechanistically, she demonstrated direct action of FGF21 on liver and the fact that the liver was FGF21 resistance in obesity. She also showed that FGF21 could induce browning of adipose tissue, thus enhancing energy expenditure and was the first to report a link between serum FGF21 and non-alcoholic fatty liver disease (NAFLD) in humans.

In seminal work, Maratos-Flier identified the orexigenic neuropeptide MCH and showed that deletion of MCH was associated with a lean, hyper-metabolic phenotype, whereas overexpression was associated with increased susceptibility to obesity.

Using a model of NAFLD she found that FGF21-KO accelerated progression of NAFLD to steatohepatitis, whereas FGF21 treatment could prevent fatty liver in mice consuming a steatotic diet. She also showed that FGF21 plays a critical role in sugar metabolism in both mouse and humans and demonstrated a role for ChREBP in this effect, suggesting that FGF21 may serve as a fructose sensor.

Together, these studies mark Eleftheria Maratos-Flier as one of the leading endocrine researchers in the U.S. today.