Hypothalamic tanycytes are an ERK-gated conduit for leptin into the brain

Eglantine Balland, Julie Dam, Fanny Langlet, Emilie Caron, Sophie Steculorum, Andrea Messina, S. Rasika, Anthony Falluel-Morel, Youssef Anouar, Bénédicte Dehouck, Eric Trinquet, Ralf Jockers, Sebastien G. Bouret, Vincent Prévot

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223 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)293-301
Number of pages9
JournalCell Metabolism
Volume19
Issue number2
DOIs
Publication statusPublished - 4 Feb 2014
Externally publishedYes

Cite this

Balland, E., Dam, J., Langlet, F., Caron, E., Steculorum, S., Messina, A., Rasika, S., Falluel-Morel, A., Anouar, Y., Dehouck, B., Trinquet, E., Jockers, R., Bouret, S. G., & Prévot, V. (2014). Hypothalamic tanycytes are an ERK-gated conduit for leptin into the brain. Cell Metabolism, 19(2), 293-301. https://doi.org/10.1016/j.cmet.2013.12.015