---
OA_place: publisher
OA_type: hybrid
_id: '19473'
abstract:
- lang: eng
  text: Leptin informs the brain about sufficiency of fuel stores. When insufficient,
    leptin levels fall, triggering compensatory increases in appetite. Falling leptin
    is first sensed by hypothalamic neurons, which then initiate adaptive responses.
    With regard to hunger, it is thought that leptin-sensing neurons work entirely
    via circuits within the central nervous system (CNS). Very unexpectedly, however,
    we now show this is not the case. Instead, stimulation of hunger requires an intervening
    endocrine step, namely activation of the hypothalamic–pituitary–adrenocortical
    (HPA) axis. Increased corticosterone then activates AgRP neurons to fully increase
    hunger. Importantly, this is true for 2 forms of low leptin-induced hunger, fasting
    and poorly controlled type 1 diabetes. Hypoglycemia, which also stimulates hunger
    by activating CNS neurons, albeit independently of leptin, similarly recruits
    and requires this pathway by which HPA axis activity stimulates AgRP neurons.
    Thus, HPA axis regulation of AgRP neurons is a previously underappreciated step
    in homeostatic regulation of hunger.
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Rachel J.
  full_name: Perry, Rachel J.
  last_name: Perry
- first_name: Jon M.
  full_name: Resch, Jon M.
  last_name: Resch
- 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: Joseph C.
  full_name: Madara, Joseph C.
  last_name: Madara
- first_name: Aviva
  full_name: Rabin-Court, Aviva
  last_name: Rabin-Court
- first_name: Hakan
  full_name: Kucukdereli, Hakan
  last_name: Kucukdereli
- first_name: Chen
  full_name: Wu, Chen
  last_name: Wu
- first_name: Joongyu D.
  full_name: Song, Joongyu D.
  last_name: Song
- first_name: Bradford B.
  full_name: Lowell, Bradford B.
  last_name: Lowell
- first_name: Gerald I.
  full_name: Shulman, Gerald I.
  last_name: Shulman
citation:
  ama: Perry RJ, Resch JM, Douglass AM, et al. Leptin’s hunger-suppressing effects
    are mediated by the hypothalamic–pituitary–adrenocortical axis in rodents. <i>Proceedings
    of the National Academy of Sciences</i>. 2019;116(27):13670-13679. doi:<a href="https://doi.org/10.1073/pnas.1901795116">10.1073/pnas.1901795116</a>
  apa: Perry, R. J., Resch, J. M., Douglass, A. M., Madara, J. C., Rabin-Court, A.,
    Kucukdereli, H., … Shulman, G. I. (2019). Leptin’s hunger-suppressing effects
    are mediated by the hypothalamic–pituitary–adrenocortical axis in rodents. <i>Proceedings
    of the National Academy of Sciences</i>. National Academy of Sciences. <a href="https://doi.org/10.1073/pnas.1901795116">https://doi.org/10.1073/pnas.1901795116</a>
  chicago: Perry, Rachel J., Jon M. Resch, Amelia M. Douglass, Joseph C. Madara, Aviva
    Rabin-Court, Hakan Kucukdereli, Chen Wu, Joongyu D. Song, Bradford B. Lowell,
    and Gerald I. Shulman. “Leptin’s Hunger-Suppressing Effects Are Mediated by the
    Hypothalamic–Pituitary–Adrenocortical Axis in Rodents.” <i>Proceedings of the
    National Academy of Sciences</i>. National Academy of Sciences, 2019. <a href="https://doi.org/10.1073/pnas.1901795116">https://doi.org/10.1073/pnas.1901795116</a>.
  ieee: R. J. Perry <i>et al.</i>, “Leptin’s hunger-suppressing effects are mediated
    by the hypothalamic–pituitary–adrenocortical axis in rodents,” <i>Proceedings
    of the National Academy of Sciences</i>, vol. 116, no. 27. National Academy of
    Sciences, pp. 13670–13679, 2019.
  ista: Perry RJ, Resch JM, Douglass AM, Madara JC, Rabin-Court A, Kucukdereli H,
    Wu C, Song JD, Lowell BB, Shulman GI. 2019. Leptin’s hunger-suppressing effects
    are mediated by the hypothalamic–pituitary–adrenocortical axis in rodents. Proceedings
    of the National Academy of Sciences. 116(27), 13670–13679.
  mla: Perry, Rachel J., et al. “Leptin’s Hunger-Suppressing Effects Are Mediated
    by the Hypothalamic–Pituitary–Adrenocortical Axis in Rodents.” <i>Proceedings
    of the National Academy of Sciences</i>, vol. 116, no. 27, National Academy of
    Sciences, 2019, pp. 13670–79, doi:<a href="https://doi.org/10.1073/pnas.1901795116">10.1073/pnas.1901795116</a>.
  short: R.J. Perry, J.M. Resch, A.M. Douglass, J.C. Madara, A. Rabin-Court, H. Kucukdereli,
    C. Wu, J.D. Song, B.B. Lowell, G.I. Shulman, Proceedings of the National Academy
    of Sciences 116 (2019) 13670–13679.
date_created: 2025-04-03T12:30:19Z
date_published: 2019-07-02T00:00:00Z
date_updated: 2025-07-10T11:51:42Z
day: '02'
ddc:
- '570'
doi: 10.1073/pnas.1901795116
extern: '1'
external_id:
  pmid:
  - '31213533'
fulldoi: https://doi.org/10.1073/pnas.1901795116
has_accepted_license: '1'
intvolume: '       116'
issue: '27'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-nd/4.0/
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1073/pnas.1901795116
month: '07'
oa: 1
oa_version: Published Version
page: 13670-13679
pmid: 1
publication: Proceedings of the National Academy of Sciences
publication_identifier:
  eissn:
  - 1091-6490
  issn:
  - 0027-8424
publication_status: published
publisher: National Academy of Sciences
quality_controlled: '1'
scopus_import: '1'
status: public
title: Leptin’s hunger-suppressing effects are mediated by the hypothalamic–pituitary–adrenocortical
  axis in rodents
tmp:
  image: /images/cc_by_nc_nd.png
  legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
    (CC BY-NC-ND 4.0)
  short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 116
year: '2019'
...