Abstract

This study proposes to characterize the lean phenotype in MCH knockout mice, and to ascertain the relative contributions of MCH and the two other peptides derived from the MCH gene, N-EI and N-GE. To determine the role of MCH in mediating the orexigenic or appetite inhibiting action of other neuropeptides the effect of appetite regulating peptides in MCH-/-will be assessed. In addition to examining the importance of mediating obesity in single gene models of rodent obesity, MCH-/-mice will be crossbred to leptin deficient (ob/ob) mice and leptin resistant A (agouti) mice. MCH-/- mice will be crossbred to mice with ablations NPY or orexin, other neuropeptides implicated in energy balance. Finally to determine the importance of MCH in mediating obesity in response to environmental agents, the ability of a high fat diet, MSG and GTG to cause obesity will be compared in wild type and MCH-/- animals.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK056113-03
Application #
6381581
Study Section
Endocrinology Study Section (END)
Program Officer
Smith, Philip F
Project Start
1999-09-01
Project End
2004-08-31
Budget Start
2001-09-01
Budget End
2002-08-31
Support Year
3
Fiscal Year
2001
Total Cost
$133,371
Indirect Cost

  Institution

Name
Joslin Diabetes Center
Department
Type
DUNS #
071723084
City
Boston
State
MA
Country
United States
Zip Code
02215

  Publications

Zhang, Ren; Maratos-Flier, Eleftheria; Flier, Jeffrey S (2009) Reduced adiposity and high-fat diet-induced adipose inflammation in mice deficient for phosphodiesterase 4B. Endocrinology 150:3076-82
Pissios, Pavlos (2009) Animals models of MCH function and what they can tell us about its role in energy balance. Peptides 30:2040-4
Willie, J T; Sinton, C M; Maratos-Flier, E et al. (2008) Abnormal response of melanin-concentrating hormone deficient mice to fasting: hyperactivity and rapid eye movement sleep suppression. Neuroscience 156:819-29
Bradley, Richard L; Jeon, Justin Y; Liu, Fen-Fen et al. (2008) Voluntary exercise improves insulin sensitivity and adipose tissue inflammation in diet-induced obese mice. Am J Physiol Endocrinol Metab 295:E586-94
Maratos-Flier, Eleftheria (2008) The long reach of leptin. Nat Med 14:604-6
Zhang, Ren; Dhillon, Harveen; Yin, Huali et al. (2008) Selective inactivation of Socs3 in SF1 neurons improves glucose homeostasis without affecting body weight. Endocrinology 149:5654-61
Pissios, Pavlos; Frank, Lauren; Kennedy, Adam R et al. (2008) Dysregulation of the mesolimbic dopamine system and reward in MCH-/- mice. Biol Psychiatry 64:184-91
Bradley, Richard L; Fisher, F Folliott M; Maratos-Flier, Eleftheria (2008) Dietary fatty acids differentially regulate production of TNF-alpha and IL-10 by murine 3T3-L1 adipocytes. Obesity (Silver Spring) 16:938-44
Pissios, Pavlos; Maratos-Flier, Eleftheria (2007) More than satiety: central serotonin signaling and glucose homeostasis. Cell Metab 6:345-7
Badman, Michael K; Pissios, Pavlos; Kennedy, Adam R et al. (2007) Hepatic fibroblast growth factor 21 is regulated by PPARalpha and is a key mediator of hepatic lipid metabolism in ketotic states. Cell Metab 5:426-37

Showing the most recent 10 out of 24 publications