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Nadege Briancon“Central Regulation of Energy Balance: inhibitors of cytokine signaling, adult hypothalamic neurogenesis and possible implication of chromatin modifiers.”

Abstract :

Obesity has reached alarming levels in developed and developing countries, resulting in substantial health threats such as cardiovascular diseases and diabetes.
Since the discovery of the adipokine leptin more than 15 years ago by Lasker-awarded Jeffrey Friedman, our understanding of brain-peripheral tissue interactions and their roles in the regulation of body energy balance has increased dramatically. Nonetheless, much remained to be discovered to have a fully integrative picture of how those multiple endocrine and neuroendocrine cues trigger and modulate cascades of signal transduction pathways and transcriptional responses. In Jeff Flier’s lab, we focused on some of those subcellular responses, with a particular interest for leptin. It is now widely acknowledged that most cases of chronic obesity and subsequent health complications are the results of the development of a state of resistance to the anorexigenic leptin hormone. We used transgenic mouse models to try to understand how leptin resistance occurs with chronic cafeteria-diet feeding, ultimately leading to obesity.

I will present our most recent studies pertaining to the roles of two inhibitors of cytokine signaling, SOCS-3 and PTP-1B, in the control of body weight and glucose homeostasis by the brain. Despite an unexpected phenotype displayed by the brain-specific Cre-expressing mice that we used to generate our conditional double knock-out mice, we were able to reveal gene-specific, additive and synergistic effects of SOCS-3 and PTP-1B in regulating adiposity, glucose homeostasis and body size. I will also discuss our new findings that chronic high fat diet feeding affects adult hypothalamic neurogenesis, and what this means for the plasticity of that tissue. Finally, I will briefly introduce my interest for chromatin modifiers in the brain and their regulation by changing metabolic cues. 

Selected publications

McNay, D.E., Briancon, N., Kokoeva, M., Maratos-Flier, E., Flier, J.S. Diet-induced obesity inhibits remodelling of the hypothalamic arcuate nucleus energy balance circuit in the mouse. Accepted for publication in JCI, Oct 26th, 2011.

Briancon, N., McNay, D.E., Maratos-Flier, E., Flier, J.S. (2010) Combined Neural Inactivation of SOCS-3 and PTP-1B Reveal Additive, Synergistic, and Factor-Specific Roles in the Regulation of Body Energy Balance. Diabetes 59(12), 3074-84.

Daniela Cota