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Cited by 63Neuroinflammation and Neurodegeneration MechanismsAdipokines, Inflammation, and Metabolic DiseasesNeurological Disease Mechanisms and Treatments

Distinct contributions of hyperglycemia and high-fat feeding in metabolic syndrome-induced neuroinflammation.

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Wanrooy, Brooke J., Kumar, Kathryn Prame, Wen, Shu Wen, Qin, Cheng Xue, Ritchie, Rebecca H., Wong, Connie H. Y.·2018·Journal of Neuroinflammation
DOI 10.1186/s12974-018-1329-8PMC PMC6198529
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Abstract

BACKGROUND: High-fat feeding and hyperglycemia, key risk factors for the development of metabolic syndrome (MetS), are emerging to associate with increased risk of developing dementia and cognitive decline. Despite this, clinical and experimental studies have yet to elucidate the specific contributions of either high-fat feeding or hyperglycemia to potential neuroinflammatory components. In this study, we delineate these individual components of MetS in the development of neuroinflammation. METHODS: Male C57Bl/6 J adult mice were treated with either citrate vehicle (CIT) or streptozotocin (STZ; 55 mg/kg) 3, 5 and 7 days before commencement of either a normal or high-fat diet for 9 or 18 weeks. By creating separate models of high-fat feeding, STZ-induced hyperglycemia, as well as in combination, we were able to delineate the specific effects of a high-fat diet and hyperglycemia on the brain. Throughout the feeding regime, we measured the animals' body weight and fasting blood glucose levels. At the experimental endpoint, we assessed plasma levels of insulin, glycated haemoglobin and performed glucose tolerance testing. In addition, we examined the effect of high fat-feeding and hyperglycemia on the levels of systemic inflammatory cytokines, gliosis in the hippocampus and immune infiltration in cerebral hemispheric tissue. Furthermore, we used intravital multiphoton microscopy to assess leukocyte-endothelial cell interactions in the cerebral vasculature of mice in vivo. RESULTS: granulocytes to the cerebral microvasculature in vivo. Moreover, we provided evidence that these changes were independent of the systemic inflammation associated with high-fat feeding. CONCLUSIONS: Hyperglycemia alone preferentially induces microglial numbers and astrocytosis in the hippocampus and is associated with the peripheral recruitment of leukocytes to the cerebrovasculature, but not systemic inflammation. High-fat feeding alone, and in combination with hyperglycemia, increases the systemic pro-inflammatory cytokine milieu but does not result in brain-specific immune gliosis. These results shed light on the specific contributions of high-fat feeding and hyperglycemia as key factors of MetS in the development of neuroinflammation.

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  • Previous HFD studies have been associated with increased microglial activity in wild-type mice.

    “Previous HFD studies have been associated with increased microglial activity in wild-type mice (Rivera et al., 2013; Wanrooy et al., 2018).”

    From Plcg2M28L Interacts With High Fat/High Sugar Diet to Accelerate Alzheimer’s Disease-Relevant Phenotypes in Mice (2022) · cites this paper as Wanrooy et al., 2018

    The Results section (“Hyperglycemia increases microglia numbers and activates astrocytes”; page unavailable) reports increased hippocampal microglia in mice given STZ on a control diet, but not in either high-fat-diet group. The paper therefore does not support citing its HFD findings as evidence of increased microglial activity in wild-type mice; its measured outcome was microglial number rather than activity. (LLM, conf=0.78)

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  • These data are consistent with the induction of diet-induced obesity (DIO) that has been previously reported for B6 mice.

    “These data are consistent with the induction of diet-induced obesity (DIO) that has been previously reported for B6 mice (Wanrooy et al., 2018).”

    From Plcg2M28L Interacts With High Fat/High Sugar Diet to Accelerate Alzheimer’s Disease-Relevant Phenotypes in Mice (2022) · cites this paper as Wanrooy et al., 2018

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Cited by

Sorted by citations

Authors
Wanrooy, B. J., Kumar, K. P., Wen, S. W., Qin, C. X., Ritchie, R. H., & Wong, C. H. Y.
Affiliations
  • Monash Medical Centre (AU)
  • Baker Heart and Diabetes Institute (AU)
Corresponding author
Wong, Connie H. Y.
ORCID
Venue
Journal of Neuroinflammation
Publisher
Springer Science and Business Media LLC
Published
2018-10-22
Volume
15
Issue
1
Pages
293-293
ISSN
1742-2094 (ISSN-L)
DOI
10.1186/s12974-018-1329-8
PMC
PMC6198529
OpenAlex
W2896559737
Cited by
63
References
4
Citations by year
2026: 7 · 2025: 4 · 2024: 15 · 2023: 7 · 2022: 10 · 2021: 7 · 2020: 7 · 2019: 4 · 2013: 2
FWCI
2.02
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Neuroinflammation (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Monash University Research Portal (Monash University) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Minerva Access (University of Melbourne) (submittedVersion, cc-by)
Funders
  • National Health and Medical Research Council (1059960)
  • National Heart Foundation of Australia (100863)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords
metabolic syndrome, neuroinflammation, hyperglycemia, high-fat diet, streptozotocin-induced diabetes, microglia, astrocyte activation, gliosis, hippocampus, leukocyte recruitment, cerebral microvasculature, leukocyte-endothelium interaction, dementia risk, cognitive decline
MeSH terms
Animals, Antibiotics, Antineoplastic, Blood Glucose, Calcium-Binding Proteins, Disease Models, Animal, Encephalitis, Fasting, Hyperglycemia, Immune System, Insulin, Leukocytes, Male, Mice, Inbred C57BL, Microfilament Proteins, Nerve Tissue Proteins, Neurons, Streptozocin, Cytokines, Microglia, Metabolic Syndrome, Mice, Diet, High-Fat

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