Eleftheria Maratos-Flier, M.D.

Associate Professor of Medicine

Beth Israel Deaconess Medical Center
Division of Endocrinology
Room 380F
99 Brookline Ave.
Boston, MA 02215
Telephone: 617-667-2151
Fax: 617- 667-2927
Email: emaratos@bidmc.harvard.edu
Predocs: 0 Postdocs: 4 Completed PhD's: 0

The major interest of my laboratory is analyzing neural pathways that regulate energy balance and defining the relationship between feeding, motivation and addiction.

We initially focused on the role of the hypothalamic neuropeptide, melanin concentrating hormone (MCH) in integrating signals from the environment to the Central Nervous System. MCH neurons project widely throughout the brain and there is particularly dense projection to the striatum. This led to us to studies on the role of MCH in regulating dopamine pathways, particularly the mesoaccumbens pathway. Using genetic models we have shown that lean mice without MCH have increased dopaminergic tone and altered behavior as well as a number of biochemical compensations. We have also found that obese mice without leptin have drastically reduced dopaminergic tone associated with major deficits in striatal function.

Thus our current studies examine pathways from fat to hypothalamus and from hypothalamus to striatum critical in regulating feeding behavior, energy balance and “motivated behavior.” Investigation of relevant pathways requires integrating a variety of techniques including behavioral, biochemical and molecular studies. In addition we are examining the relationship of these pathways to addictive behavior.

My laboratory initially discovered the orexigenic role of MCH using RT-PCR differential display, describing the increased expression in the hypothalamus of the leptin deficient ob/ob mouse and subsequently demonstrating that administration of MCH intracerebroventricularly into rodents led to a rapid and reproducible increase in feeding behavior. In addition we made mice lacking MCH and found that these animals were lean and resistant to diet induced obesity.

References:

• Segal-Lieberman G, Bradley RL, Kokkotou E, Carlson M, Trobmly DJ, Wang X, Bates S, Myers MG Jr., Flier JS, Maratos-Flier E. Melanin-concentrating hormone is a critical mediator of the leptin deficient phenotype. Proc Natl Acad Sci U S A. 2003;100(17):10085-90.
• Kokkotou E, Jeon JY, Wang X, Marino FE, Carlson M, Trombly DJ, Maratos-Flier E. Mice with MCH ablation resist diet induced obesity through strain specific mechanisms. Am J Physiology Reg. Integ.Comp. Physiol. 2005. 289:R117-124
• Jeon JY, Bradley RL, Kokkotou E, Marino FE, Wang X, Pissios P, Maratos-Flier E. MCH-/- Mice are Resistant to Aging Associated Increases in Body Weight and Insulin. Diabetes. 2006. 55:428-34