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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.

Original publication

DOI

10.1073/pnas.1212137110

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

2013

Volume

110

Pages

1512 - 1517

Keywords

Animals Appetite Regulation/*physiology Blood-Brain Barrier/physiology Capillary Permeability Eating/physiology Fasting/physiology Ghrelin/*blood Hypothalamus/blood supply/cytology/*physiology Male Median Eminence/blood supply/cytology/physiology Mice Mice, Inbred C57BL Mice, Transgenic Microscopy, Fluorescence, Multiphoton Models, Neurological Neurons/physiology