Amyloid Precursor Protein and Proinflammatory Changes Are Regulated in Brain and Adipose Tissue in a Murine Model of High Fat Diet-Induced Obesity
Open accessAbstract
BACKGROUND: Middle age obesity is recognized as a risk factor for Alzheimer's disease (AD) although a mechanistic linkage remains unclear. Based upon the fact that obese adipose tissue and AD brains are both areas of proinflammatory change, a possible common event is chronic inflammation. Since an autosomal dominant form of AD is associated with mutations in the gene coding for the ubiquitously expressed transmembrane protein, amyloid precursor protein (APP) and recent evidence demonstrates increased APP levels in adipose tissue during obesity it is feasible that APP serves some function in both disease conditions. METHODOLOGY/PRINCIPAL FINDINGS: To determine whether diet-induced obesity produced proinflammatory changes and altered APP expression in brain versus adipose tissue, 6 week old C57BL6/J mice were maintained on a control or high fat diet for 22 weeks. Protein levels and cell-specific APP expression along with markers of inflammation and immune cell activation were compared between hippocampus, abdominal subcutaneous fat and visceral pericardial fat. APP stimulation-dependent changes in macrophage and adipocyte culture phenotype were examined for comparison to the in vivo changes. CONCLUSIONS/SIGNIFICANCE: Adipose tissue and brain from high fat diet fed animals demonstrated increased TNF-α and microglial and macrophage activation. Both brains and adipose tissue also had elevated APP levels localizing to neurons and macrophage/adipocytes, respectively. APP agonist antibody stimulation of macrophage cultures increased specific cytokine secretion with no obvious effects on adipocyte culture phenotype. These data support the hypothesis that high fat diet-dependent obesity results in concomitant pro-inflammatory changes in brain and adipose tissue that is characterized, in part, by increased levels of APP that may be contributing specifically to inflammatory changes that occur.
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High fat diet is thought to contribute directly to several key aspects of AD, including increased accumulation of Aβ, tau hyperphosphorylation, and inflammation of peripheral organs and brain.
“High fat diet is thought to contribute directly to several key aspects of AD, including increased accumulation of Aβ, tau hyperphosphorylation, and inflammation of peripheral organs and brain [595–597].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [596]
Obesity stimulates microglia and increases recruitment of peripheral monocytes to the central nervous system.
“Recent studies have also found that obesity stimulates microglia and enhances the recruitment of peripheral monocytes to the CNS [16, 17]).”
From Microglial dysfunction in brain aging and Alzheimer's disease (2014) · cites this paper as [16]
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Amyloid precursor protein expression is induced by tumor necrosis factor α in 3T3‐L1 adipocytes
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Cognitive decline and dementia in diabetes mellitus: mechanisms and clinical implications
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An investigation into physical frailty as a link between the gut microbiome and cognitive health
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Obesity increases nociceptive activation of the trigeminal system
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- Authors
- Puig, K. L., Floden, A. M., Adhikari, R., Golovko, M. Y., & Combs, C. K.
- Affiliations
- University of North Dakota (US)
- Corresponding author
- Combs, Colin K.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-01-19
- Volume
- 7
- Issue
- 1
- Pages
- e30378
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3261903
- OpenAlex
- W1964645662
- Cited by
- 152
- References
- 102
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 13 · 2023: 9 · 2022: 11 · 2021: 8 · 2020: 21 · 2019: 8 · 2018: 12 · 2017: 11 · 2016: 11 · 2015: 8 · 2014: 15 · 2013: 9 · 2012: 5
- FWCI
- 8.83
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Science Foundation (0639227)
- National Institutes of Health
- National Institute on Aging (R01AG026330)
- National Center for Research Resources (1P20RR17699, P20RR017699)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- amyloid precursor protein, obesity, high-fat diet, chronic inflammation, Alzheimer's disease, adipose tissue, brain, microglial activation, macrophage activation, TNF-α, hippocampus, visceral fat, subcutaneous adipose tissue, adipocytes, neuroinflammation
- MeSH terms
- Adipose Tissue, Animals, Brain, Inflammation, Male, Mice, Inbred C57BL, Obesity, Amyloid beta-Protein Precursor, Mice, Diet, High-Fat
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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