Evidence map›Paper›PMID 41254427›Full record

ArticleMolecular neurobiology2025

Adiponectin Signaling Ameliorates Cognitive Dysfunction in Type 2 Diabetic Mice by Activating the Hippocampal AdipoR2-PPARα/CREB Pathway.

Hongyan Gong, Yanli Liu, Liu Xia, Bochao Niu, Jian Kong, Bin Wang, Xu Lin, Lin Lin, Yanlin Bi

Abstract read
PubMed Publisher
In one paragraph

Article in Molecular neurobiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Hongyan GongMOE Key Laboratory for Neuroinformation, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China.
Yanli LiuDepartment of Anesthesiology, Qingdao Municipal Hospital, Qingdao Hospital of Health and Rehabilitation Sciences University, Qingdao, China.
Liu XiaDepartment of Anesthesiology, Qingdao Municipal Hospital, Qingdao Hospital of Health and Rehabilitation Sciences University, Qingdao, China.
Bochao NiuMOE Key Laboratory for Neuroinformation, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China.
Jian KongDepartment of Anesthesiology, Qingdao Municipal Hospital, Qingdao Hospital of Health and Rehabilitation Sciences University, Qingdao, China.
Bin WangDepartment of Anesthesiology, Qingdao Municipal Hospital, Qingdao Hospital of Health and Rehabilitation Sciences University, Qingdao, China.
Xu LinDepartment of Anesthesiology, Qingdao Municipal Hospital, Qingdao Hospital of Health and Rehabilitation Sciences University, Qingdao, China.
Lin LinDepartment of Anesthesiology, Qingdao Municipal Hospital, Qingdao Hospital of Health and Rehabilitation Sciences University, Qingdao, China. linlin@qdsslyy.wecom.work.
Yanlin BiDepartment of Anesthesiology, Qingdao Municipal Hospital, Qingdao Hospital of Health and Rehabilitation Sciences University, Qingdao, China. biyanlin@qdu.edu.cn.

Funding

Natural Science Foundation of Qingdao Municipality YCTS2025-0112Qingdao Key Medical and Health Discipline 2024A077
6 · The paper itself

Abstract

Diabetes-Associated Cognitive Impairment (DACI) is a significant neurological complication of Type 2 Diabetes Mellitus (T2DM). This study investigates the role of the hippocampal adiponectin (APN) system in DACI and the therapeutic potential of AdipoRon, an oral APN receptor agonist. Using a high-fat diet/streptozotocin-induced T2DM mouse model, we found that cognitive deficits were associated with a significant downregulation of hippocampal adiponectin receptor 2 (AdipoR2), which was predominantly localized to neurons. Oral AdipoRon administration (50 and 100 mg/kg/day for 2 weeks) reversed these cognitive impairments and improved metabolic parameters. Mechanistically, these benefits were linked to the upregulation of hippocampal AdipoR2, restoration of postsynaptic proteins (PSD95, GluA1), and attenuation of neuroinflammation, as evidenced by reduced microglial and astrocyte activation. Furthermore, AdipoRon activated the hippocampal PPARα/CREB signaling pathway. In vitro experiments using high-glucose-treated HT22 hippocampal neurons confirmed that AdipoRon's neuroprotective effects, including improved CREB phosphorylation and reduced oxidative stress, were mediated via a PPARα-dependent mechanism. In conclusion, our findings highlight hippocampal AdipoR2 dysregulation as a key factor in DACI and establish AdipoRon as a promising therapeutic agent that acts through the AdipoR2/PPARα/CREB pathway. This positions AdipoRon as a candidate for further investigation in the prevention and treatment of DACI.

Indexed as

AdiponectinCognitive DysfunctionCyclic AMP Response Element-Binding ProteinDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 2HippocampusPPAR alphaReceptors, AdiponectinSignal TransductionAnimalsMaleMiceMice, Inbred C57BLNeuronsPiperidinesAdiponectinadiponectin receptor 2, mouseAdipoRonCyclic AMP Response Element-Binding ProteinPiperidinesPPAR alphaReceptors, AdiponectinAdipoRonCognitive impairmentPPARαSynaptic plasticityType 2 diabetes mellitus

Identifiers

PMID41254427

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.