Journal article
A hypothalamic circuit for anticipating future changes in energy balance
Neuron (Cambridge, Mass.), Vol.114(6), pp.3043-3060.e9
08/2026
DOI: 10.1016/j.neuron.2026.05.010
PMID: 42235510
Abstract
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 PVH
neurons strongly activates AgRP neurons. Lastly, chronic silencing of PVH
neurons causes persistent hypophagia. This PVH
-to-AgRP-neuron circuit, by anticipating and preventing negative energy balance, provides an important new dimension of hunger regulation.
Details
- Title: Subtitle
- A hypothalamic circuit for anticipating future changes in energy balance
- Creators
- Samuel J Walker - Beth Israel Deaconess Medical CenterElijah D Lowenstein - Beth Israel Deaconess Medical CenterAmelia M Douglass - Beth Israel Deaconess Medical CenterCallum M P Thomas - Beth Israel Deaconess Medical CenterJoseph C Madara - Beth Israel Deaconess Medical CenterHakan Kucukdereli - Beth Israel Deaconess Medical CenterEunice A Barbosa-Meillon - Beth Israel Deaconess Medical CenterJenkang Tao - Beth Israel Deaconess Medical CenterJon M Resch - University of IowaBradford B Lowell - Beth Israel Deaconess Medical Center
- Resource Type
- Journal article
- Publication Details
- Neuron (Cambridge, Mass.), Vol.114(6), pp.3043-3060.e9
- DOI
- 10.1016/j.neuron.2026.05.010
- PMID
- 42235510
- NLM abbreviation
- Neuron
- ISSN
- 0896-6273
- eISSN
- 1097-4199
- Publisher
- Elsevier
- Grant note
- BADERC and BNORC transgenic cores (NIH): P30DK057521, P30DK046200 NIH: S10OD028635, R01DK134427, R01DK096010, R01DK075632 Boston Area Diabetes Endocrinology Research Centers: P30DK135043 EMBO Long-Term Fellowship: 770-2018 T32 Postdoctoral Training Fellowship: 5T32DK007516 Charles A. King Trust Postdoctoral Research Fellowship program K99 Career Development Award: K99HL144923
We thank all members of the B.B.L. laboratory for helpful discussions. We thank the BADERC and BNORC transgenic cores (NIH P30DK057521 and P30DK046200) for performing embryo injections to generate knockin mouse lines. We also thank the BIDMC Energy Balance Core (supported by NIH S10OD028635 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 Core. We thank Chen Wu for assistance in designing knockin mouse lines. This work was supported by the NIH (R01DK134427, R01DK096010, and R01DK075632 to B.B.L.). Authors were supported by an EMBO Long-Term Fellowship (770-2018, S.J.W.), a T32 Postdoctoral Training Fellowship (5T32DK007516, E.D.L.), the Charles A. King Trust Postdoctoral Research Fellowship program (A.M.D.), and a K99 Career Development Award (K99HL144923, J.M.R.).
- Language
- English
- Electronic publication date
- 06/03/2026
- Date published
- 08/2026
- Academic Unit
- Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology
- Record Identifier
- 9985174607802771
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