Median eminence blood flow influences food intake by regulating ghrelin access to the metabolic brain
Nicola Romanò, … , Patrice Mollard, Marie Schaeffer
Nicola Romanò, … , Patrice Mollard, Marie Schaeffer
Published December 27, 2022
Citation Information: JCI Insight. 2023;8(3):e165763. https://doi.org/10.1172/jci.insight.165763.
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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 2

Optogenetic stimulation in NG2-ChR2 mice in vivo at the ME modifies blood flow and vessel diameter.

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Optogenetic stimulation in NG2-ChR2 mice in vivo at the ME modifies bloo...
(A) Confocal images depicting a ventral view of the ME in an NG2-ChR2 mouse (scale: 100 μm, 140 μm Z-projection; red: NG2-ChR2, green: FITC-lectin) and showing NG2DsRed cellular bodies and processes line ME capillaries. (B) Schematic of the in vivo optogenetic manipulation and imaging setup of blood flow at the ME (protocol adapted from ref. 45). Vessel parenchyma was labeled with D2-dextran. (C) Still image from an in vivo movie of blood flow at the ME in an NG2-ChR2 mouse at the start of laser stimulation (see also Supplemental Video 1) (scale: 50 μm, single Z-plane). (D) Quantification of RBC velocity in control and NG2-ChR2 mice before, during, and after 40 minutes of laser stimulation (473 nm, 50 ms, 1 Hz, 400 nm fiber at <0.5 mm of tissue). Data are presented as mean ± SEM. RBC velocity is significantly reduced during laser stimulation in NG2-ChR2 mice (n = 3–6 mice/condition, 5–10 vessels/mouse, *P < 0.05, 2-way ANOVA). (E) Still images from an in vivo movie of blood flow at the ME in an NG2-ChR2 mouse at the start of laser stimulation (left panel) and after 10 seconds of stimulation (right panel) (see also Supplemental Video 2) (scale: 50 μm, single Z-plane). Arrows indicate visible vessel constriction. Numbers indicate vessels analyzed in F. (F) Quantification of vessel constriction in movie in E. Data are presented as mean ± SEM. Diameter was measured along vessels 1 to 5 times in each vessel. Data are presented as mean ± SEM. (G) Quantification of percentage change in vessel diameters in the ME after more than 10 seconds of laser stimulation in control or NG2-ChR2 mice shows a reduction of mean vessel diameter in NG2-ChR2 mice during laser stimulation compared with basal conditions (n = 3 mice/condition, 5–10 vessels/mouse, ***P < 0.001, Mann-Whitney). Data are presented as mean ± SEM.