Learn more about the people and groups that further research at the Joslin Diabetes Center  |  Select an application from the list below:  |  Search JoslinResearch.org  |  Learn about JoslinResearch.org and its features  |  Contact us with questions or to let us know about problems  |  Login to use all our features
Joslin Diabetes Center Website
  Harvard Medical School
Joslin Research Home  
Harvard Medical School Joslin Research Home
Welcome to the Joslin Research Website                     
 
  Joslin Investigator:
   
  
EMF
 
Investigator Specifics:
Professional Details:
Publications
CV not available

Member of Section:

Current Fellows, Students, or Lab Members:
Yan Nie
Pavlos Pissios
Gabriella Segal-Leiberman
Annette Wai K Tso

Past Fellows, etc.:
Cristina De Alvaro
Justin Jeon
Efi Kokkotou
Nicholas Tritos


 
 
Eleftheria  Maratos-Flier, MD
Investigator
Joslin Diabetes Center
Associate Professor of Medicine
Harvard Medical School
 
7/1/1981 -  
 
 Description of Research

Obesity is a significant risk factor for the development of type 2 diabetes. Although the prevalence of obesity is common, the causes are poorly understood. One approach to the elucidation of molecular mechanisms for hypothalamic dysfunction which may contribute to increased appetite in obesity is to identify mRNAs that are abnormally regulated in obesity.

Dr. Maratos-Flier and colleagues have utilized PCR differential display to identify changes in expression of mRNAs and proteins that might be important in appetite regulation in the hypothalamus of obese (ob/ob) rodents. Using this technique, they have found that mRNA for the neuropeptide melanin concentrating hormone (MCH) is overexpressed in the obese state. While this peptide has been previously identified in the lateral hypothalamus of mammals (an area known to be important in appetite), its function is unclear. Dr. Maratos-Flier and colleagues have found that MCH mRNA levels increase with fasting in both normal and ob/ob mice. In addition, they have found that injection of MCH into the lateral ventricle of the brain of rats leads to a significant increase in food intake.

Preliminary data suggest that MCH may interact with the melanocortin system. In the context of the observations reported here, the potential relationship between MCH and melanin stimulating hormone (MSH) are worthy of note. MCH and MSH have antagonist actions in the melanophore, a cell found in the skin of teleost fish. MCH induces aggregation of particles in the melanophore while MSH causes dispersion. MCH and MSH can antagonize each other. MCH treatment causes rats to overeat while MSH inhibits feeding. MCH and MSH can antagonize each other in a dose-dependent manner.

In reptiles and amphibians MCH, at high concentrations, has an MSH-like action, presumably by interacting with one or more of the melanocortin receptors. Interestingly, in another genetic model of obesity, the Avy yellow mouse, there is ectopic expression of another MSH antagonist, termed the agouti protein, which can also bind to melanocortin receptors and antagonize the action of MSH. It thus becomes reasonable to speculate that one mechanism by which the agouti protein may cause obesity would be to mimic the action of the peptide MCH in the hypothalamus.

Current studies involve extending studies of MCH action and physiology in order to assess its role as a regulator of feeding behavior and in order to understand mechanisms by which it may interact with other factors that are abnormal in the obese state.


Selected References:

Qu, D., Ludwig, D.S., Gammeltoft, S., Piper, M., Pelleymounter, M.A., Cullen, M.J., Mathes, W.F., Przypek, J., Kanarek, R., Maratos-Flier, E., A Role for Melanin-concentrating Hormone in the Central Regulation of Feeding Behaviour, Nature, 1996, 380: 243-247.

Shimada, M., Tritos, N.A., Lowell, BB., Flier, J.S., Maratos-Flier E., Absence of melanin concentrating hormone produces hypophagia and a lean phenotype. Nature, 1998, 396:670-674.

Ludwig, D.S., Tritos, N.A., Mastaitis, J.W., Kulkarni, R., Kokkotou, E., Lowell, B.B., Flier, J.S., Maratos-Flier, E., Melanin-concentrating hormone overexpression in transgenic mice leads to obesity and insulin resistance. J. Clin. Invest., 2001, 107: 379-386.

Kokkotou, E.G., Tritos, N.A., Mastaitis, J.W., Slieker, L., Maratos-Flier, E. Melanin concentrating hormone receptor is a target of leptin action in the mouse brain. Endocrinology, 2001, 142:680-686.

Segal-Lieberman G, Trombly DJ, Juthani V, Wang X, Maratos-Flier E. NPY ablation in C57BL/6 mice leads to mild obesity and to an impaired refeeding response to fasting.
Am J Physiol Endocrinol Metab. 2003 Jun;284(6):E1131-9.

Pissios P, Trombly DJ, Tzameli I, Maratos-Flier E. Melanin-concentrating hormone receptor 1 activates extracellular signal-regulated kinase and synergizes with G(s)-coupled pathways. Endocrinology. 2003 Aug;144(8):3514-23.

Segal-Lieberman G, Bradley RL, Kokkotou E, Carlson M, Trombly DJ, 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 Aug 1 [Epub ahead of print]



Biographical Sketch:

Eleftheria (Terry) Maratos-Flier, M.D., is an Investigator at Joslin Diabetes Center, Assistant Professor of Medicine at Harvard Medical School and Associate Physician at Brigham and Women's Hospital. She earned her M.D. degree from Mount Sinai Medical School and completed residency training at George Washington University and Beth Israel Hospital, Boston. She joined Joslin as a Fellow in 1981 and was promoted to Instructor in 1984 and Assistant Professor in 1987. She is a former Mary K. Iacocca Fellow at Joslin. Originally interested in diabetogenic viruses, she became interested in appetite regulation and obesity in 1992.