Distinct roles of AdipoR1 and AdipoR2 in modulating neuronal firing homeostasis in response to adiponectin and AdipoRon
6 affiliations
- 1State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School
- 2NIAAA/NIH
- 3Institute for Future Human Habitats, Tsinghua University Shenzhen International Graduate School
- 4Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University
- 5Department of Otolaryngology, Head and Neck Surgery, Shenzhen Children’s Hospital
- 6Department of Neonatology, Shenzhen Children’s Hospital
Abstract
Background The regulation of neuronal network activity depends on interactions between intrinsic circuit mechanisms and metabolic signals. Adiponectin (APN) is a peripheral adipokine whose receptors are present in the central nervous system (CNS), but whether APN/APN receptor (AdipoR) signaling shapes network-level firing dynamics remains incompletely understood. Methods We used multi-electrode array (MEA) recordings in WT, APN-KO, AdipoR1-KO, and AdipoR2-KO primary cortical cultures to examine APN/AdipoR-associated regulation of network-level firing dynamics. Genetic and pharmacological experiments with native APN and the synthetic AdipoR agonist AdipoRon (AR) were complemented by dose-response, washout, time-matched control, developmental-control, ELISA, and bicuculline-challenge assays in neuronal cultures and human forebrain organoids. Results AR modulated WT network activity in a concentration-dependent manner, with strong suppression at higher concentrations and smaller or bidirectional effects at lower concentrations. APN was detectable in neuron-conditioned medium, supporting local APN-related signaling in the culture system. APN-KO and AdipoR1-KO cultures showed increased firing-rate-related activity relative to matched controls, whereas AdipoR2-KO cultures showed reduced basal firing. Native APN and AR produced distinct temporal profiles. In bicuculline-disinhibited networks, AR suppressed network firing, whereas APN did not acutely silence the networks in the same manner. Conclusion These data support a role for AdipoR signaling in neuronal network balance and indicate non-identical contributions of AdipoR1 and AdipoR2 to firing-rate control, bursting, and synchrony. Collectively, these findings identify AdipoR1 and AdipoR2 as differential regulators of firing homeostasis and establish a metabolic pathway for the homeostatic control of neuronal network excitability.
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BibTeX
@article{jia2026distinct,
title = {{Distinct roles of AdipoR1 and AdipoR2 in modulating neuronal firing homeostasis in response to adiponectin and AdipoRon}},
author = {Xiaoli Jia and Chengyou Zheng and Qichao Gong and Yue Hu and Tahir Ali and Shoupeng Wei and Jianxiang Huang and Zhangting Wang and Ping Xiao and Shupeng Li and Jinxing Feng},
journal = {Cell Communication and Signaling},
year = {2026},
month = jul,
doi = {10.1186/s12964-026-03049-x},
url = {https://doi.org/10.1186/s12964-026-03049-x},
note = {CC BY},
}
RIS
TY - JOUR
TI - Distinct roles of AdipoR1 and AdipoR2 in modulating neuronal firing homeostasis in response to adiponectin and AdipoRon
AU - Xiaoli Jia
AU - Chengyou Zheng
AU - Qichao Gong
AU - Yue Hu
AU - Tahir Ali
AU - Shoupeng Wei
AU - Jianxiang Huang
AU - Zhangting Wang
AU - Ping Xiao
AU - Shupeng Li
AU - Jinxing Feng
PY - 2026
DA - 2026/07/01
JO - Cell Communication and Signaling
DO - 10.1186/s12964-026-03049-x
UR - https://doi.org/10.1186/s12964-026-03049-x
AB - Background The regulation of neuronal network activity depends on interactions between intrinsic circuit mechanisms and metabolic signals. Adiponectin (APN) is a peripheral adipokine whose receptors are present in the central nervous system (CNS), but whether APN/APN receptor (AdipoR) signaling shapes network-level firing dynamics remains incompletely understood. Methods We used multi-electrode array (MEA) recordings in WT, APN-KO, AdipoR1-KO, and AdipoR2-KO primary cortical cultures to examine APN/AdipoR-associated regulation of network-level firing dynamics. Genetic and pharmacological experiments with native APN and the synthetic AdipoR agonist AdipoRon (AR) were complemented by dose-response, washout, time-matched control, developmental-control, ELISA, and bicuculline-challenge assays in neuronal cultures and human forebrain organoids. Results AR modulated WT network activity in a concentration-dependent manner, with strong suppression at higher concentrations and smaller or bidirectional effects at lower concentrations. APN was detectable in neuron-conditioned medium, supporting local APN-related signaling in the culture system. APN-KO and AdipoR1-KO cultures showed increased firing-rate-related activity relative to matched controls, whereas AdipoR2-KO cultures showed reduced basal firing. Native APN and AR produced distinct temporal profiles. In bicuculline-disinhibited networks, AR suppressed network firing, whereas APN did not acutely silence the networks in the same manner. Conclusion These data support a role for AdipoR signaling in neuronal network balance and indicate non-identical contributions of AdipoR1 and AdipoR2 to firing-rate control, bursting, and synchrony. Collectively, these findings identify AdipoR1 and AdipoR2 as differential regulators of firing homeostasis and establish a metabolic pathway for the homeostatic control of neuronal network excitability.
SN - 1478-811X
ER -