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

doi:10.1016/j.cmet.2019.11.016

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 journal › Article › peer-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 NTS^TH 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 NTS^TH 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 language	English
Pages (from-to)	313-326.e5
Journal	Cell Metabolism
Volume	31
Issue number	2
DOIs	https://doi.org/10.1016/j.cmet.2019.11.016
Publication status	Published - 4 Feb 2020
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2019 Elsevier Inc.

Keywords

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

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10.1016/j.cmet.2019.11.016

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Aklan, I., Sayar Atasoy, N., Yavuz, Y., Ates, T., Coban, I., Koksalar, F., Filiz, G., Topcu, I. C., Oncul, M., Dilsiz, P., Cebecioglu, U., Alp, M. I., Yilmaz, B., Davis, D. R., Hajdukiewicz, K., Saito, K., Konopka, W., Cui, H., & Atasoy, D. (2020). NTS Catecholamine Neurons Mediate Hypoglycemic Hunger via Medial Hypothalamic Feeding Pathways. Cell Metabolism, 31(2), 313-326.e5. https://doi.org/10.1016/j.cmet.2019.11.016

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title = "NTS Catecholamine Neurons Mediate Hypoglycemic Hunger via Medial Hypothalamic Feeding Pathways",

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.",

keywords = "AgRP, NTS, arcuate nucleus, catecholamine, feeding, hypoglycemia, hypoglycemic unawareness, norepinephrine, tyrosine hydroxylase",

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

note = "Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",

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day = "4",

doi = "10.1016/j.cmet.2019.11.016",

language = "English",

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Aklan, I, Sayar Atasoy, N, Yavuz, Y, Ates, T, Coban, I, Koksalar, F, Filiz, G, Topcu, IC, Oncul, M, Dilsiz, P, Cebecioglu, U, Alp, MI, Yilmaz, B, Davis, DR, Hajdukiewicz, K, Saito, K, Konopka, W, Cui, H & Atasoy, D 2020, 'NTS Catecholamine Neurons Mediate Hypoglycemic Hunger via Medial Hypothalamic Feeding Pathways', Cell Metabolism, vol. 31, no. 2, pp. 313-326.e5. https://doi.org/10.1016/j.cmet.2019.11.016

TY - JOUR

T1 - NTS Catecholamine Neurons Mediate Hypoglycemic Hunger via Medial Hypothalamic Feeding Pathways

AU - Aklan, Iltan

AU - Sayar Atasoy, Nilufer

AU - Yavuz, Yavuz

AU - Ates, Tayfun

AU - Coban, Ilknur

AU - Koksalar, Fulya

AU - Filiz, Gizem

AU - Topcu, Iskalen Cansu

AU - Oncul, Merve

AU - Dilsiz, Pelin

AU - Cebecioglu, Utku

AU - Alp, Muhammed Ikbal

AU - Yilmaz, Bayram

AU - Davis, Deborah R.

AU - Hajdukiewicz, Karolina

AU - Saito, Kenji

AU - Konopka, Witold

AU - Cui, Huxing

AU - Atasoy, Deniz

PY - 2020/2/4

Y1 - 2020/2/4

N2 - 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.

AB - 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.

KW - AgRP

KW - NTS

KW - arcuate nucleus

KW - catecholamine

KW - feeding

KW - hypoglycemia

KW - hypoglycemic unawareness

KW - norepinephrine

KW - tyrosine hydroxylase

UR - http://www.scopus.com/inward/record.url?scp=85078470780&partnerID=8YFLogxK

U2 - 10.1016/j.cmet.2019.11.016

DO - 10.1016/j.cmet.2019.11.016

M3 - Article

C2 - 31839488

AN - SCOPUS:85078470780

SN - 1550-4131

VL - 31

SP - 313-326.e5

JO - Cell Metabolism

JF - Cell Metabolism

IS - 2

ER -

NTS Catecholamine Neurons Mediate Hypoglycemic Hunger via Medial Hypothalamic Feeding Pathways

Abstract

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Keywords

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