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Cited by 47Flavonoids in Medical ResearchLiver Disease Diagnosis and TreatmentMedicinal plant effects and applications

Protective effect of quercetin against the metabolic dysfunction of glucose and lipids and its associated learning and memory impairments in NAFLD rats

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Gao, Xin-Ran, Chen, Zheng, Fang, Ke, Xu, Jing-Xian, Ge, Jin-Fang·2021·Lipids in Health and Disease
DOI 10.1186/s12944-021-01590-xPMC PMC8596093
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Abstract

Background: Quercetin (QUE) is a flavonol reported with anti-inflammatory and antioxidant activities, and previous results from the group of this study have demonstrated its neuroprotective effect against lipopolysaccharide-induced neuropsychiatric injuries. However, little is known about its potential effect on neuropsychiatric injuries induced or accompanied by metabolic dysfunction of glucose and lipids. Methods: A nonalcoholic fatty liver disease (NAFLD) rat model was induced via a high-fat diet (HFD), and glucolipid parameters and liver function were measured. Behavioral performance was observed via the open field test (OFT) and the Morris water maze (MWM). The plasma levels of triggering receptor expressed on myeloid cells-1 (TREM1) and TREM2 were measured via enzyme-linked immunosorbent assay (ELISA). The protein expression levels of Synapsin-1 (Syn-1), Synaptatogmin-1 (Syt-1), TREM1 and TREM2 in the hippocampus were detected using western blotting. Morphological changes in the liver and hippocampus were detected by HE and Oil red or silver staining. Results: Compared with the control rats, HFD-induced NAFLD model rats presented significant metabolic dysfunction, hepatocyte steatosis, and impaired learning and memory ability, as indicated by the increased plasma concentrations of total cholesterol (TC) and triglyceride (TG), the impaired glucose tolerance, the accumulated fat droplets and balloon-like changes in the liver, and the increased escaping latency but decreased duration in the target quadrant in the Morris water maze. All these changes were reversed in QUE-treated rats. Moreover, apart from improving the morphological injuries in the hippocampus, treatment with QUE could increase the decreased plasma concentration and hippocampal protein expression of TREM1 in NAFLD rats and increase the decreased expression of Syn-1 and Syt-1 in the hippocampus. Conclusions: These results suggested the therapeutic potential of QUE against NAFLD-associated impairment of learning and memory, and the mechanism might involve regulating the metabolic dysfunction of glucose and lipids and balancing the protein expression of synaptic plasticity markers and TREM1/2 in the hippocampus.

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  • Imbalance of TREM2 expression is involved in neuronal injury induced by high cholesterol and is related to LPS-induced hyperactivation of microglia and increased secretion of inflammatory factors.

    “The results of our previous studies showed that the imbalance of TREM2 expression was not only involved in the process of neuronal injury induced by high cholesterol but also related to LPS-induced hyperactivation of microglia and increased secretion of inflammatory factors (X. R. Gao et al., 2021; Liu et al., 2022; Zheng et al., 2023).”

    From AD-Like Neuropsychiatric Dysfunction in a Mice Model Induced by a Combination of High-Fat Diet and Intraperitoneal Injection of Streptozotocin (2024) · cites this paper as X. R. Gao et al., 2021

    The Background reports altered hippocampal TREM2 expression in LPS-challenged rats, and the Results report a TREM1/TREM2 imbalance in high-fat-diet-induced NAFLD rats. The cited paper does not establish TREM2 involvement in neuronal injury specifically induced by high cholesterol, or link its imbalance to LPS-induced microglial hyperactivation and increased inflammatory-factor secretion. The available passages have no page numbers. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
Gao, X.-R., Chen, Z., Fang, K., Xu, J.-X., & Ge, J.-F.
Affiliations
Anhui Medical University (CN)
Corresponding author
Ge, Jin-Fang
ORCID
Venue
Lipids in Health and Disease
Publisher
Springer Science and Business Media LLC
Published
2021-11-17
Volume
20
Issue
1
Pages
164-164
ISSN
1476-511X (ISSN-L)
DOI
10.1186/s12944-021-01590-x
PMC
PMC8596093
OpenAlex
W3212928204
Cited by
47
References
4
Citations by year
2026: 6 · 2025: 10 · 2024: 10 · 2023: 11 · 2022: 9
FWCI
4.53
Type
journal article
Language
en
Open access
Licence
Locations
  • Lipids in Health and Disease (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (81870403, 81401122)
  • Key Scientific Research Platform for Collaborative Tackling of Universities and Collaborative Innovation of Public Health in Anhui Province (GXXT-2020-062)
  • Anhui Provincial Quality Engineering Project of Higher Education Institutions (2020jyxm0868)
Topics
  • Health Sciences › Medicine › Pharmacology › Flavonoids in Medical Research
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Health Sciences › Medicine › Complementary and alternative medicine › Medicinal plant effects and applications
Keywords
quercetin, non-alcoholic fatty liver disease, high-fat diet, glucose metabolism, lipid metabolism, learning and memory impairment, TREM-1, TREM2, hippocampus, synapsin-1, synaptotagmin-1, synaptic plasticity, hepatic steatosis, neuroprotection
MeSH terms
Triggering Receptor Expressed on Myeloid Cells-1, Open Field Test, Morris Water Maze Test, Animals, Disease Models, Animal, Glucose Tolerance Test, Liver, Male, Membrane Glycoproteins, Memory Disorders, Metabolic Diseases, Quercetin, Receptors, Immunologic, Blotting, Western, Rats, Sprague-Dawley, Neuroprotective Agents, Rats, Non-alcoholic Fatty Liver Disease

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