---
OA_place: repository
OA_type: green
_id: '21955'
abstract:
- lang: eng
  text: 'AgRP neurons cause hunger, the drive to seek and consume food. Their activation
    by fasting is key for survival and is thought to be triggered by feedback when
    energy stores are low. However, we know that environmental cues can also regulate
    AgRP neurons since cues that predict future food intake rapidly inhibit AgRP neurons,
    but is the converse true: can the prediction of future fasting rapidly activate
    AgRP neurons? Here, we show in mice that such rapid fasting activation of AgRP
    neurons does occur. This rapid activation is driven by excitatory input from paraventricular
    hypothalamic (PVH) neurons expressing Sim2, which are bidirectionally sensitive
    to predictions of future energy state. Thus, cognitively processed contextual
    information conveyed by PVHSim2 neurons strongly activates AgRP neurons. Lastly,
    chronic silencing of PVHSim2 neurons causes persistent hypophagia. This PVHSim2-to-AgRP-neuron
    circuit, by anticipating and preventing negative energy balance, provides an important
    new dimension of hunger regulation.'
acknowledgement: "We thank all members of the B.B.L. laboratory for helpful discussions.
  We\r\nthank the BADERC and BNORC transgenic cores (NIH P30DK057521 and\r\nP30DK046200)
  for performing embryo injections to generate knockin mouse\r\nlines. We also thank
  the BIDMC Energy Balance Core (supported by NIH\r\nS10OD028635 and the Boston Area
  Diabetes Endocrinology Research Centers, P30DK135043), where Marissa Cortopassi
  performed indirect calorimetry experiments and Alexander Banks assisted with data
  analysis and interpretation. Confocal imaging was performed at BIDMC’s Confocal
  Imaging\r\nCore. We thank Chen Wu for assistance in designing knockin mouse lines.\r\nThis
  work was supported by the NIH (R01DK134427, R01DK096010, and\r\nR01DK075632 to B.B.L.).
  Authors were supported by an EMBO Long-Term\r\nFellowship (770-2018, S.J.W.), a
  T32 Postdoctoral Training Fellowship\r\n(5T32DK007516, E.D.L.), the Charles A. King
  Trust Postdoctoral Research\r\nFellowship program (A.M.D.), and a K99 Career Development
  Award\r\n(K99HL144923, J.M.R.)."
article_processing_charge: No
article_type: original
author:
- first_name: Samuel J.
  full_name: Walker, Samuel J.
  last_name: Walker
- first_name: Elijah D.
  full_name: Lowenstein, Elijah D.
  last_name: Lowenstein
- first_name: Amelia May Barnett
  full_name: Douglass, Amelia May Barnett
  id: de5f6fda-80fb-11ef-996f-a8c4ecd8e289
  last_name: Douglass
  orcid: 0000-0001-5398-6473
- first_name: Callum M.P.
  full_name: Thomas, Callum M.P.
  last_name: Thomas
- first_name: Joseph C.
  full_name: Madara, Joseph C.
  last_name: Madara
- first_name: Hakan
  full_name: Kucukdereli, Hakan
  last_name: Kucukdereli
- first_name: Eunice A.
  full_name: Barbosa-Meillon, Eunice A.
  last_name: Barbosa-Meillon
- first_name: Jenkang
  full_name: Tao, Jenkang
  last_name: Tao
- first_name: Jon M.
  full_name: Resch, Jon M.
  last_name: Resch
- first_name: Bradford B.
  full_name: Lowell, Bradford B.
  last_name: Lowell
citation:
  ama: Walker SJ, Lowenstein ED, Douglass AM, et al. A hypothalamic circuit for anticipating
    future changes in energy balance. <i>Neuron</i>. doi:<a href="https://doi.org/10.1016/j.neuron.2026.05.010">10.1016/j.neuron.2026.05.010</a>
  apa: Walker, S. J., Lowenstein, E. D., Douglass, A. M., Thomas, C. M. P., Madara,
    J. C., Kucukdereli, H., … Lowell, B. B. (n.d.). A hypothalamic circuit for anticipating
    future changes in energy balance. <i>Neuron</i>. Elsevier. <a href="https://doi.org/10.1016/j.neuron.2026.05.010">https://doi.org/10.1016/j.neuron.2026.05.010</a>
  chicago: Walker, Samuel J., Elijah D. Lowenstein, Amelia M. Douglass, Callum M.P.
    Thomas, Joseph C. Madara, Hakan Kucukdereli, Eunice A. Barbosa-Meillon, Jenkang
    Tao, Jon M. Resch, and Bradford B. Lowell. “A Hypothalamic Circuit for Anticipating
    Future Changes in Energy Balance.” <i>Neuron</i>. Elsevier, n.d. <a href="https://doi.org/10.1016/j.neuron.2026.05.010">https://doi.org/10.1016/j.neuron.2026.05.010</a>.
  ieee: S. J. Walker <i>et al.</i>, “A hypothalamic circuit for anticipating future
    changes in energy balance,” <i>Neuron</i>. Elsevier.
  ista: Walker SJ, Lowenstein ED, Douglass AM, Thomas CMP, Madara JC, Kucukdereli
    H, Barbosa-Meillon EA, Tao J, Resch JM, Lowell BB. A hypothalamic circuit for
    anticipating future changes in energy balance. Neuron.
  mla: Walker, Samuel J., et al. “A Hypothalamic Circuit for Anticipating Future Changes
    in Energy Balance.” <i>Neuron</i>, Elsevier, doi:<a href="https://doi.org/10.1016/j.neuron.2026.05.010">10.1016/j.neuron.2026.05.010</a>.
  short: S.J. Walker, E.D. Lowenstein, A.M. Douglass, C.M.P. Thomas, J.C. Madara,
    H. Kucukdereli, E.A. Barbosa-Meillon, J. Tao, J.M. Resch, B.B. Lowell, Neuron
    (n.d.).
date_created: 2026-06-08T09:24:25Z
date_published: 2026-06-03T00:00:00Z
date_updated: 2026-06-16T08:35:11Z
day: '03'
department:
- _id: AmDo
doi: 10.1016/j.neuron.2026.05.010
external_id:
  pmid:
  - '42235510'
fulldoi: https://doi.org/10.1016/j.neuron.2026.05.010
keyword:
- hunger
- hypothalamus
- AGRP neurons
- neuroscience
- metabolism
- homeostasis
- feeding
- food intake
- energy balance
- appetite
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1101/2025.09.27.678865
month: '06'
oa: 1
oa_version: Preprint
pmid: 1
publication: Neuron
publication_identifier:
  eissn:
  - ' 1097-4199'
  issn:
  - 0896-6273
publication_status: inpress
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: A hypothalamic circuit for anticipating future changes in energy balance
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2026'
...