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Updated: Jun 14, 2025
An Adipocyte Cell Culture Model to Study the Impact of Protein and Micro-RNA Modulation on Adipocyte Function
Published on: May 4, 2021
AdipoRon exerts an antidepressant effect by inhibiting NLRP3 inflammasome activation in microglia via promoting
Yaqi Liu1, Xiying Fu2, Jiangjin Sun1
1Department of Neurology, The Second Hospital of Jilin University, Changchun, Jilin Province, China; Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, Jilin Province, China.
Abstract:
Depression is a serious mental disorder that threatens patients' physical and mental health worldwide. The activation of the NLR family pyrin domain-containing 3 (NLRP3) inflammasome is essential for microglia-mediated neuroinflammation and neuronal damage in depression. Numerous pathophysiological factors, such as mitochondrial dysfunction and impaired mitophagy, have an essential role in activating the NLRP3 inflammasome. AdipoRon is a potent adiponectin receptor agonist; however, its antidepressant effects have not been thoroughly investigated. In this study, we found that AdipoRon ameliorated depression-like behavior and neuronal damage induced by chronic unpredictable mild stress (CUMS). Further research demonstrated that AdipoRon inhibited the activation of the NLRP3 inflammasome and protected hippocampal neurons from microglial cytotoxicity by promoting mitophagy, increasing the clearance of damaged mitochondria, and reducing mtROS accumulation. Importantly, inhibition of mitophagy attenuated the antidepressant and neuroprotective effects of AdipoRon. Overall, these findings indicate that AdipoRon alleviates depression by inhibiting NLRP3 inflammasome activation in microglia via improving mitophagy.
Insights
AdipoRon, a new drug, alleviates depression by improving mitophagy and reducing neuroinflammation. This study shows AdipoRon
Area of Science:
- Neuroscience
- Pharmacology
- Cell Biology
Background:
- Depression is a global mental health issue linked to neuroinflammation.
- NLRP3 inflammasome activation in microglia contributes to neuronal damage in depression.
- Mitochondrial dysfunction and impaired mitophagy are key NLRP3 inflammasome activators.
Purpose of the Study:
- To investigate the antidepressant effects of AdipoRon, an adiponectin receptor agonist.
- To explore the underlying mechanisms of AdipoRon's action in depression models.
Main Methods:
- Utilized a chronic unpredictable mild stress (CUMS) model to induce depression-like behaviors and neuronal damage.
- Assessed the effects of AdipoRon on NLRP3 inflammasome activation, mitophagy, mitochondrial reactive oxygen species (mtROS), and microglial cytotoxicity.
- Investigated the role of mitophagy inhibition in attenuating AdipoRon's effects.
Main Results:
- AdipoRon ameliorated depression-like behavior and neuronal damage in the CUMS model.
- AdipoRon inhibited NLRP3 inflammasome activation by promoting mitophagy, enhancing clearance of damaged mitochondria, and reducing mtROS accumulation.
- Inhibition of mitophagy reversed the antidepressant and neuroprotective effects of AdipoRon.
Conclusions:
- AdipoRon demonstrates significant antidepressant and neuroprotective effects.
- AdipoRon alleviates depression by enhancing mitophagy and subsequently inhibiting NLRP3 inflammasome activation in microglia.
- Targeting mitophagy presents a potential therapeutic strategy for depression.
