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Microglia dictate the impact of saturated fat consumption on hypothalamic inflammation and neuronal function.
Open accessAbstract
Diets rich in saturated fat produce inflammation, gliosis, and neuronal stress in the mediobasal hypothalamus (MBH). Here, we show that microglia mediate this process and its functional impact. Although microglia and astrocytes accumulate in the MBH of mice fed a diet rich in saturated fatty acids (SFAs), only the microglia undergo inflammatory activation, along with a buildup of hypothalamic SFAs. Enteric gavage specifically with SFAs reproduces microglial activation and neuronal stress in the MBH, and SFA treatment activates murine microglia, but not astrocytes, in culture. Moreover, depleting microglia abrogates SFA-induced inflammation in hypothalamic slices. Remarkably, depleting microglia from the MBH of mice abolishes inflammation and neuronal stress induced by excess SFA consumption, and in this context, microglial depletion enhances leptin signaling and reduces food intake. We thus show that microglia sense SFAs and orchestrate an inflammatory process in the MBH that alters neuronal function when SFA consumption is high.
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“Multiple studies have demonstrated that microglia number increases within the mediobasal hypothalamus during diet induced obesity (Thaler et al., 2012; de Kloet et al., 2014; Valdearcos et al., 2014; Schur et al., 2015; Waise et al., 2015; Baufeld et al., 2016; Guillemot-Legris et al., 2016).”
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., 2014
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Metadata
- Authors
- Valdearcos, M., Robblee, M. M., Benjamin, D. I., Nomura, D. K., Xu, A. W., & Koliwad, S. K.
- Affiliations
- University of California, San Francisco (US)
- University of California, Berkeley (US)
- Corresponding author
- Koliwad, Suneil K.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2014-12
- Volume
- 9
- Issue
- 6
- Pages
- 2124-2138
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC4617309
- OpenAlex
- W2025131475
- Cited by
- 629
- References
- 53
- Citations by year
- 2026: 40 · 2025: 51 · 2024: 70 · 2023: 54 · 2022: 65 · 2021: 73 · 2020: 59 · 2019: 71 · 2018: 57 · 2017: 49 · 2016: 24 · 2015: 16
- FWCI
- 15.45
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institutes of Health (5k08dk080174-04)
- National Institute of Diabetes and Digestive and Kidney Diseases (T32DK061918, K08 DK080174, 5K08DK080174, P30DK063720, P30DK026743)
- 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, saturated fatty acids, diet-induced obesity, hypothalamic inflammation, mediobasal hypothalamus, neuronal stress, astrocytes, leptin signaling, food intake regulation, microglial depletion, gliosis
- MeSH terms
- Animals, Astrocytes, Cells, Cultured, Dietary Fats, Eating, Energy Metabolism, Fatty Acids, Gliosis, Hypothalamus, Inflammation, Male, Mice, Inbred C57BL, Neurons, Signal Transduction, Leptin, Mice
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