Rapid sensing of circulating ghrelin by hypothalamic appetite-modifying neurons

作者：Marie Schaeffer, Fanny Langlet, Chrystel Lafont, François Molino, David J. Hodson, Thomas Roux, Laurent Lamarque, Pascal Verdié, Emmanuel Bourrier, Bénédicte Dehouck, Jean‐Louis Banères, Jean Martínez, Pierre‐François Méry, Jacky Marie, Eric Trinquet, Jean‐Alain Fehrentz, Vincent Prévot, Patrice Mollard · 发表于：Proceedings of the National Academy of Sciences · 年份：2013 · DOI：10.1073/pnas.1212137110 · 被引用次数：314 · 研究领域：Regulation of Appetite and Obesity、Biochemical Analysis and Sensing Techniques、Adipose Tissue and Metabolism

To maintain homeostasis, hypothalamic neurons in the arcuate nucleus must dynamically sense and integrate a multitude of peripheral signals. Blood-borne molecules must therefore be able to circumvent the tightly sealed vasculature of the blood-brain barrier to rapidly access their target neurons. However, how information encoded by circulating appetite-modifying hormones is conveyed to central hypothalamic neurons remains largely unexplored. Using in vivo multiphoton microscopy together with fluorescently labeled ligands, we demonstrate that circulating ghrelin, a versatile regulator of energy expenditure and feeding behavior, rapidly binds neurons in the vicinity of fenestrated capillaries, and that the number of labeled cell bodies varies with feeding status. Thus, by virtue of its vascular connections, the hypothalamus is able to directly sense peripheral signals, modifying energy status accordingly.