Up-regulated fractalkine (FKN) and its receptor CX3CR1 are involved in fructose-induced neuroinflammation: suppression by curcumin
Abstract
Recent studies suggest that diet-induced fractalkine (FKN) stimulates neuroinflammation in animal models of obesity, yet how it occurs is unclear. This study investigated the role of FKN and it receptor, CX3CR1, in fructose-induced neuroinflammation, and examined curcumin's beneficial effect. Fructose feeding was found to induce hippocampal microglia activation with neuroinflammation through the activation of the Toll-like receptor 4 (TLR4)/nuclear transcription factor κB (NF-κB) signaling, resulting in the reduction of neurogenesis in the dentate gyrus (DG) of mice. Serum FKN levels, as well as hypothalamic FKN and CX3CR1 gene expression, were significantly increased in fructose-fed mice with hypothalamic microglia activation. Hippocampal gene expression of FKN and CX3CR1 was also up-regulated at 14d and normalized at 56d in mice fed with fructose, which were consistent with the change of GFAP. Furthermore, immunostaining showed that GFAP and FKN expression was increased in cornu amonis 1, but decreased in DG in fructose-fed mice. In vitro studies showed that GFAP and FKN expression was stimulated in astrocytes, and suppressed in mixed glial cells exposed to 48h-fructose, with the continual increase of pro-inflammatory cytokines. Thus, increased FKN and CX3CR1 may cause a cross-talk between activated glial cells and neurons, playing an important role in the development of neuroinflammation in fructose-fed mice. Curcumin protected against neuronal damage in hippocampal DG of fructose-fed mice by inhibiting microglia activation and suppressed FKN/CX3CR1 up-regulation in the neuronal network. These results suggest a new therapeutic approach to protect against neuronal damage associated with dietary obesity-associated neuroinflammation.
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Reversing neuroinflammation via targeted genetic, pharmacological, or dietary approaches that rescue behavioral anomalies supports a causal role of neuroinflammation in obesity-induced neuropathophysiology.
“Reversing neuroinflammation via targeted genetic [96,97], pharmacological [98,99], or dietary [49,100] approaches that rescue behavioral anomalies offers convincing support for a causal role of neuroinflammation in obesity-induced neuropathophysiology.”
From The menace of obesity to depression and anxiety prevalence (2022) · cites this paper as [100]
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The menace of obesity to depression and anxiety prevalence
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“Reversing neuroinflammation via targeted genetic [96,97], pharmacological [98,99], or dietary [49,100] approaches that rescue behavioral anomalies offers convincing support for a causal role of neuroinflammation in obesity-induced neuropathophysiology.”
BackgroundLi, J.-M., Yu, R., Zhang, L.-P., Wen, S.-Y., Wang, S.-J., Zhang, X.-Y., Xu, Q., & Kong, L.-D. (2019) · Microbiome · doi:10.1186/s40168-019-0713-7 · Cited by 300 · see citing works
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- Authors
- Xu, M.-X., Yu, R., Shao, L.-F., Zhang, Y.-X., Ge, C.-X., Liu, X.-M., Wu, W.-Y., Li, J.-M., & Kong, L.-D.
- Affiliations
- State Key Laboratory of Pharmaceutical Biotechnology (CN)
- Corresponding author
- Li, Jian-Mei
- Kong, Ling-Dong
- Venue
- Brain Behavior and Immunity
- Publisher
- Elsevier BV
- Published
- 2016-11
- Volume
- 58
- Pages
- 69-81
- ISSN
- 0889-1591 (ISSN-L)
- OpenAlex
- W2225947433
- Cited by
- 61
- References
- 58
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 7 · 2023: 3 · 2022: 6 · 2021: 5 · 2020: 11 · 2019: 7 · 2018: 6 · 2017: 4 · 2016: 4 · 2012: 1
- FWCI
- 3.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81025025, 81373788, 81573476, J1210026)
- Ministry of Education of the People's Republic of China (20120091110039)
- Natural Science Foundation of Jiangsu Province (BK2012725)
- National Key Research and Development Program of China (2014CB542300)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- fractalkine, CX3CR1, curcumin, microglial activation, hippocampus, dentate gyrus, neurogenesis, TLR4/NF-κB signaling, hypothalamus, astrocytes, inflammatory cytokines, diet-induced obesity, neuronal injury
- MeSH terms
- CX3C Chemokine Receptor 1, Animals, Astrocytes, Curcumin, Encephalitis, Fructose, Hippocampus, Male, Mice, Inbred ICR, Signal Transduction, Up-Regulation, Microglia, Cell Proliferation, Chemokine CX3CL1
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