Abstract

A major regulator of body composition, energy balance and food intake is leptin, an adipocytokine. Leptin circulates and has direct actions in the brain and skeletal muscle by binding to the B isoform of leptin receptor (LEPR-B). While there are actions of leptin on other cell types, such as on immune cells and endothelial cells, these are most likely not directly relevant to energy balance. Leptin action in the hypothalamus has proven to be complex. There are numerous hypothalamic nuclei that are responsive to leptin and each of these nuclei has numerous types of neurons, as defined by their neurotransmitter content. The goals of this proposal are to examine the functional importance of POMC/CART neurons, AGRP/NPY neurons and MCH neurons in mediating the effects of leptin. We have three specific aims that are targeted to these three leptin-regulated neuronal cell types.
Aim 1. Determine the role of AGRP deficiency in restoring normal fertility and mammary gland development to LEPR-B deficient females.
Aim 2. Determine the contribution of AGRP/NPY/GABA transmission from arcuate AGRP neurons to the obesity/diabetes syndrome.
Aim 3. Determine the direct and indirect regulation of MCH neurons by leptin and the significance of this regulation to the obesity/diabetes syndrome.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK057621-10
Application #
7864293
Study Section
Special Emphasis Panel (ZRG1-EMNR-J (03))
Program Officer
Hyde, James F
Project Start
2000-06-01
Project End
2011-06-30
Budget Start
2010-07-01
Budget End
2011-06-30
Support Year
10
Fiscal Year
2010
Total Cost
$390,957
Indirect Cost

  Institution

Name
Albert Einstein College of Medicine
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
110521739
City
Bronx
State
NY
Country
United States
Zip Code
10461

  Publications

Lu, Zhonglei; Marcelin, Genevieve; Bauzon, Frederick et al. (2013) pRb is an obesity suppressor in hypothalamus and high-fat diet inhibits pRb in this location. EMBO J 32:844-57
Marcelin, Genevieve; Liu, Shun-Mei; Schwartz, Gary J et al. (2013) Identification of a loss-of-function mutation in Ube2l6 associated with obesity resistance. Diabetes 62:2784-95
Israel, Davelene D; Sheffer-Babila, Sharone; de Luca, Carl et al. (2012) Effects of leptin and melanocortin signaling interactions on pubertal development and reproduction. Endocrinology 153:2408-19
Marcelin, Genevieve; Liu, Shun-Mei; Li, Xiaosong et al. (2012) Genetic control of ATGL-mediated lipolysis modulates adipose triglyceride stores in leptin-deficient mice. J Lipid Res 53:964-72
Luo, Na; Marcelin, Genevieve; Liu, Shun Mei et al. (2011) Neuropeptide Y and agouti-related peptide mediate complementary functions of hyperphagia and reduced energy expenditure in leptin receptor deficiency. Endocrinology 152:883-9
Chua Jr, Streamson (2010) SH2B1--the adaptor protein that could. Endocrinology 151:4100-2
Iqbal, Jahangir; Li, Xiaosong; Chang, Benny Hung-Junn et al. (2010) An intrinsic gut leptin-melanocortin pathway modulates intestinal microsomal triglyceride transfer protein and lipid absorption. J Lipid Res 51:1929-42
Israel, Davelene; Chua Jr, Streamson (2010) Leptin receptor modulation of adiposity and fertility. Trends Endocrinol Metab 21:10-6
Marcelin, Genevieve; Chua Jr, Streamson (2010) Contributions of adipocyte lipid metabolism to body fat content and implications for the treatment of obesity. Curr Opin Pharmacol 10:588-93
Jo, Young-Hwan; Su, Ya; Gutierrez-Juarez, Roger et al. (2009) Oleic acid directly regulates POMC neuron excitability in the hypothalamus. J Neurophysiol 101:2305-16

Showing the most recent 10 out of 24 publications