title: Hypothalamic tanycytes are an ERK-gated conduit for leptin into the brain.
abstract: 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.
authors: Inserm UMR837, Jean-Pierre Aubert Research Centre, UDSL, IMPRT, 59000 Lille, France.
authors: Eglantine
authors: E
authors: Balland
authors: Inserm U1016, CNRS UMR 8104, Institut Cochin, Univ. Paris Descartes, 75000 Paris, France.
authors: Julie
authors: J
authors: Dam
authors: Inserm UMR837, Jean-Pierre Aubert Research Centre, UDSL, IMPRT, 59000 Lille, France.
authors: Fanny
authors: F
authors: Langlet
authors: Inserm UMR837, Jean-Pierre Aubert Research Centre, UDSL, IMPRT, 59000 Lille, France.
authors: Emilie
authors: E
authors: Caron
authors: Inserm UMR837, Jean-Pierre Aubert Research Centre, UDSL, IMPRT, 59000 Lille, France.
authors: Sophie
authors: S
authors: Steculorum
authors: Inserm UMR837, Jean-Pierre Aubert Research Centre, UDSL, IMPRT, 59000 Lille, France.
authors: Andrea
authors: A
authors: Messina
authors: Inserm UMR837, Jean-Pierre Aubert Research Centre, UDSL, IMPRT, 59000 Lille, France.
authors: S
authors: S
authors: Rasika
authors: Inserm U982, University of Rouen, 76821 Mont-Saint-Aignan, France.
authors: Anthony
authors: A
authors: Falluel-Morel
authors: Inserm U982, University of Rouen, 76821 Mont-Saint-Aignan, France.
authors: Youssef
authors: Y
authors: Anouar
authors: Inserm UMR837, Jean-Pierre Aubert Research Centre, UDSL, IMPRT, 59000 Lille, France.
authors: Bénédicte
authors: B
authors: Dehouck
authors: Cisbio Bioassays, Parc Technologique Marcel Boiteux, BP84175, 30200 Codolet, France.
authors: Eric
authors: E
authors: Trinquet
authors: Inserm U1016, CNRS UMR 8104, Institut Cochin, Univ. Paris Descartes, 75000 Paris, France.
authors: Ralf
authors: R
authors: Jockers
authors: Inserm UMR837, Jean-Pierre Aubert Research Centre, UDSL, IMPRT, 59000 Lille, France.|Neuroscience Program, The Saban Research Institute, Children's Hospital Los Angeles, University of Southern California, Los Angeles, CA 90027, USA.
authors: Sebastien G
authors: SG
authors: Bouret
authors: Inserm UMR837, Jean-Pierre Aubert Research Centre, UDSL, IMPRT, 59000 Lille, France.
authors: Vincent
authors: V
authors: Prévot
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D063928:Ependymoglial Cells / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism*; D047468:Immunoprecipitation; D020738:Leptin / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction
chemical_list: D020738:Leptin