The mechanism by which the hypothalamus, and other organs, receives leptin's signal and transduce it into a pleiotypic effector response are the subjects of this proposal. The following experiments are proposed: 1) to study the origin and projections of the signaling form of the leptin receptor positive neurons in the hypothalamus, the electrophysiologic and transcriptional responses of these neurons to leptin, and their neurotransmitter profile; 2) to use the Lox-Cre system to further evaluate leptin's sites of action in the CNS and elsewhere in vivo; and 3) to study the effector response to leptin by analyzing the physiologic mechanisms by which intracerebroventricular administration of leptin leads to a reduction in adipose tissue mass.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK041096-10
Application #
2770380
Study Section
Nutrition Study Section (NTN)
Program Officer
Yanovski, Susan Z
Project Start
1989-09-20
Project End
2002-08-31
Budget Start
1998-09-01
Budget End
1999-08-31
Support Year
10
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Rockefeller University
Department
Genetics
Type
Other Domestic Higher Education
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065
Battula, Kiran Kumar; Nappanveettil, Giridharan; Nakanishi, Satoshi et al. (2015) Genetic Relatedness of WNIN and WNIN/Ob with Major Rat Strains in Biomedical Research. Biochem Genet 53:132-40
Knight, Zachary A; Schmidt, Sarah F; Birsoy, Kivanc et al. (2014) A critical role for mTORC1 in erythropoiesis and anemia. Elife 3:e01913
Berry, Ryan; Rodeheffer, Matthew S (2013) Characterization of the adipocyte cellular lineage in vivo. Nat Cell Biol 15:302-8
Birsoy, Kivanç; Berry, Ryan; Wang, Tim et al. (2011) Analysis of gene networks in white adipose tissue development reveals a role for ETS2 in adipogenesis. Development 138:4709-19
Knight, Zachary A; Hannan, K Schot; Greenberg, Matthew L et al. (2010) Hyperleptinemia is required for the development of leptin resistance. PLoS One 5:e11376
Alon, Tamar; Zhou, Ligang; Pérez, Cristian A et al. (2009) Transgenic mice expressing green fluorescent protein under the control of the corticotropin-releasing hormone promoter. Endocrinology 150:5626-32
Birsoy, Kivanc; Chen, Zhu; Friedman, Jeffrey (2008) Transcriptional regulation of adipogenesis by KLF4. Cell Metab 7:339-47
Zeigerer, Anja; Rodeheffer, Matthew S; McGraw, Timothy E et al. (2008) Insulin regulates leptin secretion from 3T3-L1 adipocytes by a PI 3 kinase independent mechanism. Exp Cell Res 314:2249-56
Alon, Tamar; Friedman, Jeffrey M (2006) Late-onset leanness in mice with targeted ablation of melanin concentrating hormone neurons. J Neurosci 26:389-97
Dobrzyn, Agnieszka; Dobrzyn, Pawel; Lee, Seong-Ho et al. (2005) Stearoyl-CoA desaturase-1 deficiency reduces ceramide synthesis by downregulating serine palmitoyltransferase and increasing beta-oxidation in skeletal muscle. Am J Physiol Endocrinol Metab 288:E599-607

Showing the most recent 10 out of 51 publications