The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.
Microglial inflammatory signaling orchestrates the hypothalamic immune response to dietary excess and mediates obesity susceptibility.
Open accessAbstract
Dietary excess triggers accumulation of pro-inflammatory microglia in the mediobasal hypothalamus (MBH), but the components of this microgliosis and its metabolic consequences remain uncertain. Here, we show that microglial inflammatory signaling determines the immunologic response of the MBH to dietary excess and regulates hypothalamic control of energy homeostasis in mice. Either pharmacologically depleting microglia or selectively restraining microglial NF-κB-dependent signaling sharply reduced microgliosis, an effect that includes prevention of MBH entry by bone-marrow-derived myeloid cells, and greatly limited diet-induced hyperphagia and weight gain. Conversely, forcing microglial activation through cell-specific deletion of the negative NF-κB regulator A20 induced spontaneous MBH microgliosis and cellular infiltration, reduced energy expenditure, and increased both food intake and weight gain even in absence of a dietary challenge. Thus, microglial inflammatory activation, stimulated by dietary excess, orchestrates a multicellular hypothalamic response that mediates obesity susceptibility, providing a mechanistic rationale for non-neuronal approaches to treat metabolic diseases.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“It has also been reported that genetic or pharmacologic treatments that increase microgliosis within the mediobasal hypothalamus are capable of inducing obesity even in the absence of dietary challenge (Valdearcos et al., 2017; Campolim et al., 2020).”
From Deletion of the Alzheimer’s disease risk gene Abi3 locus results in obesity and systemic metabolic disruption in mice (2022) · cites this paper as Valdearcos et al., 2017
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Recent studies have shown that both increased and decreased microglial inflammatory activity within the mediobasal hypothalamus can disrupt leptin/melanocortin related neuronal signaling, a pathway that is central to the regulation of energy balance (Gao et al., 2017; Valdearcos et al., 2017; Kim et al., 2019).”
From Deletion of the Alzheimer’s disease risk gene Abi3 locus results in obesity and systemic metabolic disruption in mice (2022) · cites this paper as Valdearcos et al., 2017
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Further, it has been demonstrated that reducing this dietary induced microgliosis can mitigate weight gain (Andre et al., 2017; Valdearcos et al., 2017; Kim et al., 2019).”
From Deletion of the Alzheimer’s disease risk gene Abi3 locus results in obesity and systemic metabolic disruption in mice (2022) · cites this paper as Valdearcos et al., 2017
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Central nervous system control of food intake
Schwartz, M. W., Woods, S. C., Porte, D., Seeley, R. J., & Baskin, D. G. (2000) · Nature · doi:10.1038/35007534 · Cited by 6,451
Fate Mapping Analysis Reveals That Adult Microglia Derive from Primitive Macrophages
Ginhoux, F., Greter, M., Leboeuf, M., Nandi, S., See, P., Gokhan, S., Mehler, M. F., Conway, S. J., Ng, L. G., Stanley, E. R., et al. (2010) · Science · doi:10.1126/science.1194637 · Cited by 5,175
Inflammatory Mechanisms in Obesity
Gregor, M. F., & Hotamisligil, G. S. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-031210-101322 · Cited by 3,754
Jung, S., Aliberti, J., Graemmel, P., Sunshine, M. J., Kreutzberg, G. W., Sher, A., & Littman, D. R. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.11.4106-4114.2000 · Cited by 2,632
Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor
Parkhurst, C. N., Yang, G., Ninan, I., Savas, J. N., Yates, J. R., Lafaille, J. J., Hempstead, B. L., Littman, D. R., & Gan, W.-B. (2013) · Cell · doi:10.1016/j.cell.2013.11.030 · Cited by 2,599
Identification of a unique TGF-β–dependent molecular and functional signature in microglia
Butovsky, O., Jedrychowski, M. P., Moore, C. S., Cialic, R., Lanser, A. J., Gabriely, G., Koeglsperger, T., Dake, B., Wu, P. M., Doykan, C. E., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3599 · Cited by 2,543
Elmore, M. R. P., Najafi, A. R., Koike, M. A., Dagher, N. N., Spangenberg, E. E., Rice, R. A., Kitazawa, M., Matusow, B., Nguyen, H., West, B. L., et al. (2014) · Neuron · doi:10.1016/j.neuron.2014.02.040 · Cited by 1,968
Obesity is associated with hypothalamic injury in rodents and humans.
Thaler, J. P., Yi, C.-X., Schur, E. A., Guyenet, S. J., Hwang, B. H., Dietrich, M. O., Zhao, X., Sarruf, D. A., Izgur, V., Maravilla, K. R., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci59660 · Cited by 1,857
Self-citationNew tools for studying microglia in the mouse and human CNS
Bennett, M. L., Bennett, F. C., Liddelow, S. A., Ajami, B., Zamanian, J. L., Fernhoff, N. B., Mulinyawe, S. B., Bohlen, C. J., Adil, A., Tucker, A., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1525528113 · Cited by 1,804
Self-citationIKK-β links inflammation to obesity-induced insulin resistance
Arkan, M. C., Hevener, A. L., Greten, F. R., Maeda, S., Li, Z.-W., Long, J. M., Wynshaw-Boris, A., Poli, G., Olefsky, J., & Karin, M. (2005) · Nature Medicine · doi:10.1038/nm1185 · Cited by 1,773
Cited by
Sorted by citations
Huang, Y., Xu, Z., Xiong, S., Sun, F., Qin, G., Hu, G., Wang, J., Zhao, L., Liang, Y.-X., Wu, T., et al. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0090-8 · Cited by 560
Role of astrocytes, microglia, and tanycytes in brain control of systemic metabolism
García‐Cáceres, C., Balland, É., Prévot, V., Luquet, S. H., Woods, S. C., Koch, M., Horváth, T. L., Yi, C., Chowen, J. A., Verkhratsky, A., et al. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0286-y · Cited by 343
Immunometabolism in the Brain: How Metabolism Shapes Microglial Function
Bernier, L., York, E. M., & MacVicar, B. A. (2020) · Trends in Neurosciences · doi:10.1016/j.tins.2020.08.008 · Cited by 308
Matt, S. M., & Gaskill, P. J. (2019) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-019-09851-4 · Cited by 293
Neuroinflammation after surgery: from mechanisms to therapeutic targets
Yang, T., Velagapudi, R., & Terrando, N. (2020) · Nature Immunology · doi:10.1038/s41590-020-00812-1 · Cited by 288
Metadata
- Authors
- Valdearcos, M., Douglass, J. D., Robblee, M. M., Dorfman, M. D., Stifler, D. R., Bennett, M. L., Gerritse, I., Fasnacht, R., Barres, B. A., Thaler, J. P., & Koliwad, S. K.
- Affiliations
- University of Washington (US)
- University of California, San Francisco (US)
- Stanford Medicine (US)
- Corresponding author
- Thaler, Joshua P.
- Koliwad, Suneil K.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2017-07
- Volume
- 26
- Issue
- 1
- Pages
- 185-197.e3
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC5569901
- OpenAlex
- W2727793071
- Cited by
- 477
- References
- 58
- Citations by year
- 2026: 38 · 2025: 50 · 2024: 69 · 2023: 49 · 2022: 49 · 2021: 59 · 2020: 53 · 2019: 65 · 2018: 39 · 2017: 6
- FWCI
- 22.20
- Type
- journal article
- Language
- en
- Update notices
- erratum (2018-06-05)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- American Diabetes Association (1-14-ACE-51)
- NIDDK (K08 DK088872, T32 DK7247-37, F32 DK108473-01, R01 DK103175-02)
- UCSF Diabetes Family Fund
- Nutrition Obesity Research Centers (DK098722)
- University of Washington (DK035816)
- Diabetes Research Center (DK017047)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- microglia, microglial activation, mediobasal hypothalamus, dietary excess, obesity susceptibility, NF-κB signaling, A20, energy homeostasis, hyperphagia, weight gain, myeloid cell infiltration, energy expenditure, diet-induced obesity
- MeSH terms
- Animals, Appetite Regulation, Energy Metabolism, Hyperphagia, Hypothalamus, Inflammation, Male, Mice, Inbred C57BL, Obesity, Signal Transduction, NF-kappa B, Microglia, Myeloid Cells, Mice
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 ›
Are you an author, or do you see a problem with this page? Request a review
