Director: Timothy Moran, Ph.D.
OVERVIEW
Our overall research program is aimed at identifying the roles of various neural signaling pathways in the controls of food intake and body weight. The current research takes a number of approaches. The first involves the identification of the neural representation of meal-related satiety signals. Multiple feedback signaling pathways are activated by food ingestion and the gastrointestinal presence of digestion products. We are examining how signals from multiple sites and stimulus modalities are integrated within specific brain nuclei and, in an effort to model eating disorders, how alterations in feeding patterns can influence these neural representations.
The second approach involves the identification of interactions between peripheral, within-meal, satiety signals and hypothalamic peptide systems involved in overall energy balance. We are currently examining how the activity of hypothalamic leptin, NPY, CCK, CFR, CART and melanocortin systems interact with ascending satiety pathways to alter meal size. We are also investigating how alteration in cellular energy availability and production are transduced into changes in food intake and body weight. These experiments focus on the de novo fatty acid synthesis pathway in critical hypothalamic sites and take advantage of a novel group of chemicals that inhibit the production of fatty acids and/or stimulate fatty acid oxidation. We are examining how exercise not only increases energy expenditure but also reduces food intake. These experiments focus on the regulation of peptide gene expression in hypothalamic systems involved in energy balance.
Finally, we are examining how gestational factors can bias metabolic programming to contribute to altered feeding and obesity. Experiments are conducted at multiple levels and employ behavioral, physiological and molecular in vivo and in vitro paradigms.
OUR FACULTY AND STAFF
| Timothy H. Moran, Ph.D. |
Ellen E. Ladenhiem, Ph.D., Associate Professor |
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Susan Aja, Ph.D., Assistant Professor Our research investigates how alterations in cellular energy availability and production in the hypothalamus are transduced into changes in food intake, energy expenditure, and body weight. Current experiments utilize novel compounds to alter the activities of enzymes involved in either de novo synthesis or beta-oxidation of fatty acids. The in vivo experiments in rodents examine how these chemicals and other environmental manipulations affect specific ingestive behaviors, involuntary energy expenditure, fuel utilization, and adiposity. In vitro models include neuronal cell lines, hypothalamic neurons in primary culture, and hypothalamic explants from adult animals. We measure expression of genes for hypothalamic neuropeptides involved in the regulation of energy balance, production and output of these neuropeptides, and status of energy-gauge molecules such as AMP-activated protein kinase (AMPK). |
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Kellie L. K. Tamashiro |
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 | Su Gao, Graduate Student sgao@jhmi.edu 410-955-2344 I study the molecular mechanisms underlying the hypothalamic actions of leptin, an anorexigenic hormone. Specifically, I am interested in how the pathway involving AMP kinase (AMPK), Acetyl CoA Carboxylase (ACC) and Malonyl CoA (the product of ACC catalyzed reaction) mediate the anorectic effects of leptin. The methodology involves biochemical, pharmacological and genetic approaches and I use both rodent models and cell culture systems to address the questions. |
