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

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 4

Optogenetic stimulation of NG2-positive cells at the ME decreases peripheral ghrelin access to the ME/ARH region.

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Optogenetic stimulation of NG2-positive cells at the ME decreases periph...
(A) Schematic of experimental design. Laser stimulation was applied to 24-hour-fasted animals for 30 minutes before injection of fluorescent ghrelin injection i.v. Sacrifice was 5–10 minutes postinjection. Ghr, ghrelin. (B) Confocal images of ME/ARH region 10 minutes following i.v. injection of fluorescent ghrelin (red) in a control mouse (left) and in an NG2-ChR2 mouse (right) subjected to 30 minutes of continuous laser stimulation at the level of the ME (473 nm, 50 ms, 1 Hz) (blue: DAPI) Scale: 100 μm, 12 μm Z-projection. (C) Quantification of ghrelin-labeled neurons in the whole ME/ARH region under optogenetic stimulation (15–24 slices/mouse, n = 6–7 mice/condition). Numbers were normalized to correspond to total ME length (1,200 μm; 24 slices, 50 μm thick). Data are presented as mean ± SEM. Optogenetic stimulation reduces the number of ghrelin-labeled neurons in the ME/ARH at 10 minutes after injection of ghrelin in NG2-ChR2 mice (*P < 0.05, Mann-Whitney test). (D) Confocal images of ME/ARH region 5–10 minutes following i.v. injection of fixable 10 kDa dextran-FITC (green) in a control mouse (left) and in an NG2-ChR2 mouse (right) subjected to 30 minutes of continuous laser stimulation at the level of the ME (473 nm, 50 ms, 1 Hz) (blue: DAPI). Scale: 100 μm, 16 μm Z-projection. (E) Quantification of the diffusion area of fixable 10 kDa dextran-FITC into the ME/ARH region under optogenetic stimulation (2–4 slices/mouse, n = 3 mice/condition). Data are presented as mean ± SEM. Optogenetic stimulation reduces the area of diffusion of 10 kDa dextran into the ME/ARH at 5–10 minutes postinjection in NG2-ChR2 mice (***P < 0.001, Mann-Whitney test).