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Median eminence blood flow influences food intake by regulating ghrelin access to the metabolic brain
Nicola Romanò, Chrystel Lafont, Pauline Campos, Anne Guillou, Tatiana Fiordelisio, David J. Hodson, Patrice Mollard, Marie Schaeffer
Nicola Romanò, Chrystel Lafont, Pauline Campos, Anne Guillou, Tatiana Fiordelisio, David J. Hodson, Patrice Mollard, Marie Schaeffer
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Research Article Metabolism

Median eminence blood flow influences food intake by regulating ghrelin access to the metabolic brain

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Abstract

Central integration of peripheral appetite-regulating signals ensures maintenance of energy homeostasis. Thus, plasticity of circulating molecule access to neuronal circuits involved in feeding behavior plays a key role in the adaptive response to metabolic changes. However, the mechanisms involved remain poorly understood despite their relevance for therapeutic development. Here, we investigated the role of median eminence mural cells, including smooth muscle cells and pericytes, in modulating gut hormone effects on orexigenic/anorexigenic circuits. We found that conditional activation of median eminence vascular cells impinged on local blood flow velocity and altered ghrelin-stimulated food intake by delaying ghrelin access to target neurons. Thus, activation of median eminence vascular cells modulates food intake in response to peripheral ghrelin by reducing local blood flow velocity and access to the metabolic brain.

Authors

Nicola Romanò, Chrystel Lafont, Pauline Campos, Anne Guillou, Tatiana Fiordelisio, David J. Hodson, Patrice Mollard, Marie Schaeffer

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Figure 3

Optogenetic stimulation of NG2-positive cells at the ME decreases and delays ghrelin-stimulated food intake.

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Optogenetic stimulation of NG2-positive cells at the ME decreases and de...
(A) Schematic of experimental design. Mice were analyzed preimplantation, and several times postimplantation (with or without laser stimulation), leaving at least 1 week recovery postsurgery and between ghrelin (Ghr) challenges. After 3 hours’ habituation attached to the optic fiber, the laser was switched on, and ghrelin was injected i.p. 30 minutes after switching on the laser. Picture depicts a representative coronal slice of an implanted brain. Scale: 2 mm. (B) Food intake episodes over time after injection of ghrelin i.p. in a representative NG2-ChR2 mouse (left) and a single transgenic ROSA26-ChR2 mouse (right). Individual lines correspond to repetitions of the experiment in the same animal. Black and blue lines correspond to feeding episodes elicited by ghrelin injection when mice are attached to optic fibers and laser is off or on, respectively. (C) Total number of food intake episodes over the course of 1 hour after ghrelin injection i.p. (n = 6–7 mice/condition, *P < 0.05, mixed-effect model). (D) Delay to first feeding episode after ghrelin injection i.p. (n = 6–7 mice/condition, **P < 0.01, mixed-effect model). Boxes represent median with interquartile range; whiskers represent min to max range.

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