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Adrenergic modulation of melanocortin pathway by hunger signals

Author

Listed:
  • Nilufer Sayar-Atasoy

    (University of Iowa)

  • Connor Laule

    (University of Iowa)

  • Iltan Aklan

    (University of Iowa)

  • Hyojin Kim

    (University of Iowa)

  • Yavuz Yavuz

    (Yeditepe University)

  • Tayfun Ates

    (University of Iowa)

  • Ilknur Coban

    (Heidelberg University)

  • Fulya Koksalar-Alkan

    (Wayne State University)

  • Jacob Rysted

    (University of Iowa)

  • Debbie Davis

    (University of Iowa)

  • Uday Singh

    (University of Iowa)

  • Muhammed Ikbal Alp

    (Istanbul Medipol University)

  • Bayram Yilmaz

    (Yeditepe University)

  • Huxing Cui

    (University of Iowa)

  • Deniz Atasoy

    (University of Iowa)

Abstract

Norepinephrine (NE) is a well-known appetite regulator, and the nor/adrenergic system is targeted by several anti-obesity drugs. To better understand the circuitry underlying adrenergic appetite control, here we investigated the paraventricular hypothalamic nucleus (PVN), a key brain region that integrates energy signals and receives dense nor/adrenergic input, using a mouse model. We found that PVN NE level increases with signals of energy deficit and decreases with food access. This pattern is recapitulated by the innervating catecholaminergic axon terminals originating from NTSTH-neurons. Optogenetic activation of rostral-NTSTH → PVN projection elicited strong motivation to eat comparable to overnight fasting whereas its inhibition attenuated both fasting-induced & hypoglycemic feeding. We found that NTSTH-axons functionally targeted PVNMC4R-neurons by predominantly inhibiting them, in part, through α1-AR mediated potentiation of GABA release from ARCAgRP presynaptic terminals. Furthermore, glucoprivation suppressed PVNMC4R activity, which was required for hypoglycemic feeding response. These results define an ascending nor/adrenergic circuit, NTSTH → PVNMC4R, that conveys peripheral hunger signals to melanocortin pathway.

Suggested Citation

  • Nilufer Sayar-Atasoy & Connor Laule & Iltan Aklan & Hyojin Kim & Yavuz Yavuz & Tayfun Ates & Ilknur Coban & Fulya Koksalar-Alkan & Jacob Rysted & Debbie Davis & Uday Singh & Muhammed Ikbal Alp & Bayra, 2023. "Adrenergic modulation of melanocortin pathway by hunger signals," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42362-8
    DOI: 10.1038/s41467-023-42362-8
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    References listed on IDEAS

    as
    1. Wenwen Cheng & Ermelinda Ndoka & Jessica N. Maung & Warren Pan & Alan C. Rupp & Christopher J. Rhodes & David P. Olson & Martin G. Myers, 2021. "NTS Prlh overcomes orexigenic stimuli and ameliorates dietary and genetic forms of obesity," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    2. Carolyn W. Roman & Victor A. Derkach & Richard D. Palmiter, 2016. "Genetically and functionally defined NTS to PBN brain circuits mediating anorexia," Nature Communications, Nature, vol. 7(1), pages 1-11, September.
    3. B. Sofia Beas & Xinglong Gu & Yan Leng & Omar Koita & Shakira Rodriguez-Gonzalez & Morgan Kindel & Bridget A. Matikainen-Ankney & Rylan S. Larsen & Alexxai V. Kravitz & Mark A. Hoon & Mario A. Penzo, 2020. "A ventrolateral medulla-midline thalamic circuit for hypoglycemic feeding," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
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