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2 results on '"Institut pour la Recherche sur le Cancer de Lille (U837 INSERM - IRCL)"'

1. Hypothalamic Tanycytes Are an ERK-Gated Conduit for Leptin into the Brain

Author

Sowmyalakshmi Rasika, Eric Trinquet, Eglantine Balland, Sebastien G. Bouret, Bénédicte Dehouck, Emilie Caron, Ralf Jockers, Julie Dam, Andrea Messina, Youssef Anouar, Sophie M. Steculorum, Fanny Langlet, Anthony Falluel-Morel, Vincent Prevot, Institut pour la Recherche sur le Cancer de Lille (U837 INSERM - IRCL), Institut pour la recherche sur le cancer de Lille [Lille] (IRCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche Jean-Pierre AUBERT - Neurosciences et Cancer -JPArc [Lille], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cisbio Bioassays [Codolet, France] (Innovation Management / CbB), The Saban Research Institute [Los Angeles, CA, États-Unis], Children’s Hospital Los Angeles [Los Angeles]-University of Southern California (USC), Institut pour la recherche sur le cancer de Lille [Lille] (IRCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Southern California (USC)-Children’s Hospital Los Angeles [Los Angeles], and Prevot, Vincent

Subjects
Leptin, Male, MAPK/ERK pathway, medicine.medical_specialty, Physiology, Blotting, Western, Ependymoglial Cells, Hypothalamus, Biology, Article, Mice, Internal medicine, medicine, Animals, Immunoprecipitation, Premovement neuronal activity, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Receptor, Molecular Biology, 2. Zero hunger, Leptin receptor, Tanycyte, digestive, oral, and skin physiology, Brain, Cell Biology, Mice, Inbred C57BL, medicine.anatomical_structure, Endocrinology, Median eminence, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neuron, hormones, hormone substitutes, and hormone antagonists, Signal Transduction
Abstract

International audience; Leptin secreted by adipocytes acts on the brain to reduce food intake by regulating neuronal activity in the mediobasal hypothalamus (MBH). Obesity is associated with resistance to high circulating leptin levels. Here, we demonstrate that peripherally administered leptin activates its receptor (LepR) in median eminence tanycytes followed by MBH neurons, a process requiring tanycytic ERK signaling and the passage of leptin through the cerebrospinal fluid. In mice lacking the signal-transducing LepRb isoform or with diet-induced obesity, leptin taken up by tanycytes accumulates in the median eminence and fails to reach the MBH. Triggering ERK signaling in tanycytes with EGF reestablishes leptin transport, elicits MBH neuron activation and energy expenditure in obese animals, and accelerates the restoration of leptin sensitivity upon the return to a normal-fat diet. ERK-dependent leptin transport by tanycytes could thus play a critical role in the pathophysiology of leptin resistance, and holds therapeutic potential for treating obesity.

Published
2014
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2. Tanycytic VEGF-A Boosts Blood-Hypothalamus Barrier Plasticity and Access of Metabolic Signals to the Arcuate Nucleus in Response to Fasting

Author

Sebastien G. Bouret, Peter Carmeliet, Danièle Mazur, Andrea Messina, Vincent Prevot, Eglantine Balland, Serge Luquet, Ambrose A. Dunn-Meynell, Amélie Lacombe, Bénédicte Dehouck, Fanny Langlet, Massimiliano Mazzone, Barry E. Levin, Institut pour la Recherche sur le Cancer de Lille (U837 INSERM - IRCL), Institut pour la recherche sur le cancer de Lille [Lille] (IRCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche Jean-Pierre AUBERT - Neurosciences et Cancer -JPArc [Lille], Institut de médecine predictive et de recherche thérapeutique (IMPRT), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Veterans Affairs Medical Center, Rutgers New Jersey Medical School (NJMS), Rutgers University System (Rutgers), Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), VIB Vesalius Research Center (VRC), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), The Saban Research Institute [Los Angeles, CA, États-Unis], Children’s Hospital Los Angeles [Los Angeles]-University of Southern California (USC), Université d'Artois (UA), Prevot, Vincent, Institut pour la recherche sur le cancer de Lille [Lille] (IRCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lille-UNICANCER-Université de Lille-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), and University of Southern California (USC)-Children’s Hospital Los Angeles [Los Angeles]

Subjects
Male, Vascular Endothelial Growth Factor A, medicine.medical_specialty, Animals, Arcuate Nucleus of Hypothalamus, Blood-Brain Barrier, Deoxyglucose, Ependyma, Fasting, Mice, Mice, Inbred C57BL, Signal Transduction, Tight Junctions, Endothelium, Physiology, Biology, Inbred C57BL, Energy homeostasis, 03 medical and health sciences, 0302 clinical medicine, Arcuate nucleus, Internal medicine, medicine, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Molecular Biology, 030304 developmental biology, 0303 health sciences, Tight junction, Tanycyte, Cell Biology, Endocrinology, medicine.anatomical_structure, Hypothalamus, Median eminence, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Signal transduction, 030217 neurology & neurosurgery
Abstract

International audience; The delivery of blood-borne molecules conveying metabolic information to neural networks that regulate energy homeostasis is restricted by brain barriers. The fenestrated endothelium of median eminence microvessels and tight junctions between tanycytes together compose one of these. Here, we show that the decrease in blood glucose levels during fasting alters the structural organization of this blood-hypothalamus barrier, resulting in the improved access of metabolic substrates to the arcuate nucleus. These changes are mimicked by 2-deoxyglucose-induced glucoprivation and reversed by raising blood glucose levels after fasting. Furthermore, we show that VEGF-A expression in tanycytes modulates these barrier properties. The neutralization of VEGF signaling blocks fasting-induced barrier remodeling and significantly impairs the physiological response to refeeding. These results implicate glucose in the control of blood-hypothalamus exchanges through a VEGF-dependent mechanism and demonstrate a hitherto unappreciated role for tanycytes and the permeable microvessels associated with them in the adaptive metabolic response to fasting.

Published
2013
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