Journal article
Reciprocal activity of AgRP and POMC neurons governs coordinated control of feeding and metabolism
Nature metabolism, Vol.6(3), pp.473-493
03/2024
DOI: 10.1038/s42255-024-00987-z
PMCID: PMC10963273
PMID: 38378998
Abstract
Agouti-related peptide (AgRP)-expressing and proopiomelanocortin (POMC)-expressing neurons reciprocally regulate food intake. Here, we combine non-interacting recombinases to simultaneously express functionally opposing chemogenetic receptors in AgRP and POMC neurons for comparing metabolic responses in male and female mice with simultaneous activation of AgRP and inhibition of POMC neurons with isolated activation of AgRP neurons or isolated inhibition of POMC neurons. We show that food intake is regulated by the additive effect of AgRP neuron activation and POMC neuron inhibition, while systemic insulin sensitivity and gluconeogenesis are differentially modulated by isolated-versus-simultaneous regulation of AgRP and POMC neurons. We identify a neurocircuit engaging Npy1R-expressing neurons in the paraventricular nucleus of the hypothalamus, where activated AgRP neurons and inhibited POMC neurons cooperate to promote food consumption and activate Th
neurons in the nucleus tractus solitarii. Collectively, these results unveil how food intake is precisely regulated by the simultaneous bidirectional interplay between AgRP and POMC neurocircuits.
Details
- Title: Subtitle
- Reciprocal activity of AgRP and POMC neurons governs coordinated control of feeding and metabolism
- Creators
- Alain J De Solis - University Hospital CologneAlmudena Del Río-Martín - University Hospital CologneJan Radermacher - University of CologneWeiyi Chen - University Hospital CologneLukas Steuernagel - University Hospital CologneCorinna A Bauder - University Hospital CologneFynn R Eggersmann - University of CologneDonald A Morgan - University of IowaAnna-Lena Cremer - Max Planck Institute for Metabolism ResearchMichael Sué - Max Planck Institute for Metabolism ResearchMaximilian Germer - Max Planck Institute for Biology of AgeingChristian Kukat - Max Planck Institute for Biology of AgeingStefan Vollmar - Max Planck Institute for Metabolism ResearchHeiko Backes - Max Planck Institute for Metabolism ResearchKamal Rahmouni - Fraternal Order of Eagles Diabetes Research Center, University of Iowa Carver College of Medicine, Iowa City, IA, USAPeter Kloppenburg - University of CologneJens C Brüning - National Center for Diabetes Research (DZD), Neuherberg, Germany. bruening@sf.mpg.de
- Resource Type
- Journal article
- Publication Details
- Nature metabolism, Vol.6(3), pp.473-493
- DOI
- 10.1038/s42255-024-00987-z
- PMID
- 38378998
- PMCID
- PMC10963273
- NLM abbreviation
- Nat Metab
- eISSN
- 2522-5812
- Grant note
- ARC-Neurohet 752319 / EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020) KL 762/7-1 / Deutsche Forschungsgemeinschaft (German Research Foundation)
- Language
- English
- Electronic publication date
- 02/20/2024
- Date published
- 03/2024
- Academic Unit
- Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984560423402771
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