NTS Catecholamine Neurons Mediate Hypoglycemic Hunger via Medial Hypothalamic Feeding Pathways

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Aklan I., Sayar Atasoy N., Yavuz Y., Ates T., Coban I., Koksalar F., ...More

Cell Metabolism, vol.31, no.2, pp.313, 2020 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 31 Issue: 2
  • Publication Date: 2020
  • Doi Number: 10.1016/j.cmet.2019.11.016
  • Journal Name: Cell Metabolism
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE, MEDLINE
  • Page Numbers: pp.313
  • Keywords: AgRP, arcuate nucleus, catecholamine, feeding, hypoglycemia, hypoglycemic unawareness, norepinephrine, NTS, tyrosine hydroxylase
  • Istanbul Medipol University Affiliated: Yes


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. Increased appetite is a key line of defense against hypoglycemia. Aklan et al. have identified an ascending pathway from the brainstem to the hypothalamus that is required for hypoglycemia-induced food intake.