Adiponectin Deficiency is a Critical Factor Contributing to Cognitive Dysfunction in Obese Mice After Sevoflurane Exposure

Overview

Journal Mol Med

Publisher Biomed Central

Specialties General Medicine
Molecular Biology

Date 2024 Oct 16

PMID 39415089

Authors

John Man Tak Chu

Suki Pak Wing Chiu

Jiaqi Wang

Raymond Chuen Chung Chang

Gordon Tin Chun Wong

Affiliations

Soon will be listed here.

Abstract

Background: The number of major operations performed in obese patients is expected to increase given the growing prevalence of obesity. Obesity is a risk factor for a range of postoperative complications including perioperative neurocognitive disorders. However, the mechanisms underlying this vulnerability are not well defined. We hypothesize that obese subjects are more vulnerable to general anaesthesia induced neurotoxicity due to reduced levels of adiponectin. This hypothesis was tested using a murine surgical model in obese and adiponectin knockout mice exposed to the volatile anaesthetic agent sevoflurane.

Methods: Obese mice were bred by subjecting C57BL/6 mice to a high fat diet. Cognitive function, neuroinflammatory responses and neuronal degeneration were assessed in both obese and lean mice following exposure to 2 h of sevoflurane to confirm sevoflurane-induced neurotoxicity. Thereafter, to confirm the role of adiponectin deficiency in, adiponectin knockout mice were established and exposed to the sevoflurane. Finally, the neuroprotective effects of adiponectin receptor agonist (AdipoRon) were examined.

Results: Sevoflurane triggered significant cognitive dysfunction, neuroinflammatory responses and neuronal degeneration in the obese mice while no significant impact was observed in the lean mice. Similar cognitive dysfunction and neuronal degeneration were also observed in the adiponectin knockout mice after sevoflurane exposure. Administration of AdipoRon partially prevented the deleterious effects of sevoflurane in both obese and adiponectin knockout mice.

Conclusions: Our findings demonstrate that obese mice are more susceptible to sevoflurane-induced neurotoxicity and cognitive impairment in which adiponectin deficiency is one of the underlying mechanisms. Treatment with adiponectin receptor agonist ameliorates this vulnerability. These findings may have therapeutic implications in reducing the incidence of anaesthesia related neurotoxicity in obese subjects.

Citing Articles

AdipoRon's Impact on Alzheimer's Disease-A Systematic Review and Meta-Analysis.

Barbalho S, Fornari Laurindo L, de Oliveira Zanuso B, da Silva R, Gallerani Caglioni L, Nunes Junqueira de Moraes V Int J Mol Sci. 2025; 26(2).

PMID: 39859201 PMC: 11765103. DOI: 10.3390/ijms26020484.

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