Imprimer

Leptin normally enters the brain mediobasal hypothalamus (MBH) to decrease food intake and increase energy expenditure. Obesity is associated with resistance to high circulating leptin levels. 

jockers

 

A collaboration between the team of Vincent Prevot (Inserm UMR837, Jean-Pierre Aubert Research Centre, UDSL, IMPRT, Lille), the team of Ralf Jockers (Institut Cochin, Inserm U1016, CNRS 8104, Université Paris Descartes) and the company CisBio BioAssays (Parc Technologique Marcel Boiteux, Codolet) allowed to understand how the anorexigenic hormone, leptin, penetrates into the hypothalamus to activate neurons that govern energy balance. Balland et al elucidate molecular mechanisms by which tanycyte, a highly specialized hypothalamic glial cell, regulates transport of leptin across the blood-brain barrier (BBB).

Leptin normally enters the brain mediobasal hypothalamus (MBH) to decrease food intake and increase energy expenditure. Obesity is associated with resistance to high circulating leptin levels. The mechanism of leptin resistance could rise from a defect in both leptin entry and action in the MBH target neurons. The median eminence (ME), a BBB structure located at the bottom of the third ventricles, regulates the passage of blood-borne signals to the cerebrospinal fluid (CSF) and MBH neurons.
Balland et al. demonstrate that peripherally administered leptin first activates its receptor (LepR) in ME tanycytes followed after by MBH neurons. Tanycytes are able to internalize leptin through clathrin-coated vesicles and release leptin into the the cerebrospinal fluid, a process requiring tanycytic ERK signaling. In mice lacking the signal-transducing LepRb isoform or with diet-induced obesity, leptin taken up by tanycytes accumulates in the ME 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.

 

Sources :

 

Hypothalamic Tanycytes Are an ERK-Gated Conduit for Leptin into the Brain
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 SG And Prévot V.
Cell Metabolism 2014 19, 293–301

Previews: Hypothalamic Tanycytes: Gatekeepers to Metabolic Control
Gao Y., Tschop M.H. and Luquet S.
Cell Metabolism 2014 19, 173-175