NTS Catecholamine Neurons Mediate Hypoglycemic Hunger via Medial Hypothalamic Feeding Pathways

Iltan Aklan, Nilufer Sayar Atasoy, Yavuz Yavuz, Tayfun Ates, Ilknur Coban, Fulya Koksalar, Gizem Filiz, Iskalen Cansu Topcu, Merve Oncul, Pelin Dilsiz, Utku Cebecioglu, Muhammed Ikbal Alp, Bayram Yilmaz, Deborah R. Davis, Karolina Hajdukiewicz, Kenji Saito, Witold Konopka, Huxing Cui, Deniz Atasoy*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

90 Citations (Scopus)

Abstract

Glucose is the essential energy source for the brain, whose deficit, triggered by energy deprivation or therapeutic agents, can be fatal. Increased appetite is the key behavioral defense against hypoglycemia; however, the central pathways involved are not well understood. Here, we describe a glucoprivic feeding pathway by tyrosine hydroxylase (TH)-expressing neurons from nucleus of solitary tract (NTS), which project densely to the hypothalamus and elicit feeding through bidirectional adrenergic modulation of agouti-related peptide (AgRP)- and proopiomelanocortin (POMC)-expressing neurons. Acute chemogenetic inhibition of arcuate nucleus (ARC)-projecting NTSTH neurons or their target, AgRP neurons, impaired glucoprivic feeding induced by 2-Deoxy-D-glucose (2DG) injection. Neuroanatomical tracing results suggested that ARC-projecting orexigenic NTSTH neurons are largely distinct from neighboring catecholamine neurons projecting to parabrachial nucleus (PBN) that promotes satiety. Collectively, we describe a circuit organization in which an ascending pathway from brainstem stimulates appetite through key hunger neurons in the hypothalamus in response to hypoglycemia.

Original languageEnglish
Pages (from-to)313-326.e5
JournalCell Metabolism
Volume31
Issue number2
DOIs
Publication statusPublished - 4 Feb 2020
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2019 Elsevier Inc.

Keywords

  • AgRP
  • NTS
  • arcuate nucleus
  • catecholamine
  • feeding
  • hypoglycemia
  • hypoglycemic unawareness
  • norepinephrine
  • tyrosine hydroxylase

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