12月6日 Karine Gauthier: Selective activation/inactivation of the thyroid hormone signaling pathway in the neurons: the metabolic consequences


报告题目:Selective activation/inactivation of the thyroid hormone signaling pathway in the neurons: the metabolic consequences
报告人:Karine Gauthier, Senior scientist CR1 CNRS ENS Lyon, Lyon, FRANCE
主持人:翁杰敏 教授
报告时间:12月6日 下午13:30(周三下午)
报告地点: 生命科学学院534报告厅
主办单位:生命科学学院,科技处
 
报告人简介: Karine Gauthier has been working in the thyroid hormone field for the last 20 years or so. She did her PhD in the Lab of Jacques Samarut (1996-2000) at the ENS in Lyon. She generated during these years several of the knock-out mice currently used in a number of labs to study Thyroid Hormone Receptors (TR) function.  She participated to the early collaborative effort to characterize those mice, for a better understanding of TR roles during early postnatal development. She then moved for her postdoctoral training to David Mangelsdorf’s Lab at UTSW Medical Center in Dallas where she was an HHMI research associate (2001-2004). She kept on studying there nuclear receptors function using knock-out mouse models. She had special interest in finding new ligands for PXR and in studying the role of LXR in fat metabolism and macrophage functions. She came back in France in 2004 as a permanent investigator in Jacques Samarut lab, where she directed a small group of people. She studies the role of Thyroid Hormones and TR in the control of lipid and glucose metabolism in peripheral tissues and their involvement in metabolic diseases development. She obtained her HDR (habilitation to direct research) in 2013. She is currently working at the IGFL in Lyon in the group of Frédéric Flamant. The focus of her studies is now to understand how endogenous brain signaling is involved in regulating energy expenditure, using both tissue selective inhibition and activation of TR in mice.
She participates to a European Network on nuclear receptors and coordinates an ANR project headed by Jacques Samarut. She has a total number of 33 publications all in well recognized international journals.
She is a member of the ETA, reviews papers for ATVB ,molecular endocrinology, endocrinology, scientific reports, and Plos one regularly and has been selected or invited to give talks in many national and international congresses in the past years. She has been part of many PhD defense committees.
 
报告内容简介:Introduction: Thyroid hormone (T3) regulates lipid/glucose homeostasis and energy expenditure. Given its ability to decrease cholesterol and body weight, T3 appears as an attractive candidate to fight metabolic disorders such as atherosclerosis and obesity. However T3 can’t be use as a safe drug because of its many unwanted side effects especially in bone, muscle and heart. T3 signals via its binding to its nuclear receptors TRs, some transcription factors expressed in most tissues. It was classically accepted that T3 was acting in a given tissue through the locally expressed TR. However recent studies by different groups suggest that at least some of the metabolic peripheral actions of T3 might actually result from its central action. Indeed local injection of T3 in the brain induces both liver gluconeogenesis and energy expenditure as efficiently as when administered to the whole body.
Objectives: Here we assess the role of endogenous T3 brain signaling under physiological stressors known to be perceived by the hypothalamus and to trigger increase energy expenditure: cold exposure and high fat diet.
Results: Using mice mutants, we showed that neuron selective inactivation of T3 signaling impaired adaptive thermogenesis in response to high fat diet but not cold exposure. Moreover, even though both TR1 and TR are expressed in the hypothalamus, TR1 seems to be the only critical to fight diet induced obesity. Conversely neuronal TR seems to be the major player for T3 regulated glucose metabolism in liver. Some new pharmacological approach has also been used to selectively deliver T3 to the brain and study the potential benefits versus side effects of such compounds.
Conclusions: Endogenous neuronal TR signaling is involved in adaptive thermogenesis each TR fulfilling some specific functions.