Inflammation and insulin/IGF-1 resistance as the possible link between obesity and neurodegeneration
Abstract
Obesity is a growing epidemic that contributes to several brain disorders including Alzheimer's, Parkinson's, and Huntington's diseases. Obesity could promote these diseases through several different mechanisms. Here we review evidence supporting the involvement of two recently recognized factors linking obesity with neurodegeneration: the induction of pro-inflammatory cytokines and onset of insulin and insulin-like growth factor 1 (IGF-1) resistance. Excess peripheral pro-inflammatory mediators, some of which can cross the blood brain barrier, may trigger neuroinflammation, which subsequently exacerbates neurodegeneration. Insulin and IGF-1 resistance leads to weakening of neuroprotective signaling by these molecules and can contribute to onset of neurodegenerative diseases.
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Alterations in insulin signaling are associated with mitochondrial dysfunction and lead to activation of pro-inflammatory pathways, increased oxidative/nitrosative stress and glutamate excitotoxicity, resulting in neuroinflammation and neurodegeneration.
“Alterations in insulin signaling are associated with mitochondrial dysfunction and lead to the activation of pro-inflammatory pathways, as well as increased oxidative/nitrosative stress and glutamate excitotoxicity, which result in neuroinflammation and neurodegeneration [111].”
From Cognitive remission: a novel objective for the treatment of major depression? (2016) · cites this paper as [111]
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References 243 · Cited by 182
- Authors
- Spielman, L. J., Little, J. P., & Klegeris, A.
- Affiliations
- University of British Columbia, Okanagan Campus (CA)
- Corresponding author
- Klegeris, Andis
- Venue
- Journal of Neuroimmunology
- Publisher
- Elsevier BV
- Published
- 2014-08
- Volume
- 273
- Issue
- 1-2
- Pages
- 8-21
- ISSN
- 0165-5728 (ISSN-L)
- OpenAlex
- W2075044986
- Cited by
- 182
- References
- 243
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 4 · 2023: 10 · 2022: 19 · 2021: 17 · 2020: 20 · 2019: 17 · 2018: 7 · 2017: 14 · 2016: 33 · 2015: 18 · 2014: 4
- FWCI
- 1.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuroimmunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Natural Sciences and Engineering Research Council of Canada
- Jack Brown and Family AD Research Foundation
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- obesity, neurodegeneration, neuroinflammation, insulin resistance, IGF-1 resistance, inflammatory cytokines, blood-brain barrier, Alzheimer's disease, Parkinson's disease, Huntington's disease
- MeSH terms
- Animals, Humans, Inflammation, Insulin Resistance, Insulin-Like Growth Factor I, Obesity, Cytokines, Neurodegenerative Diseases
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