Cited by 631Neuroinflammation and Neurodegeneration MechanismsRegulation of Appetite and ObesityAdipokines, Inflammation, and Metabolic Diseases

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Microglia dictate the impact of saturated fat consumption on hypothalamic inflammation and neuronal function.

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Valdearcos, Martin, Robblee, Megan M., Benjamin, Daniel I., Nomura, Daniel K., Xu, Allison W., Koliwad, Suneil K.·2014·Cell Reports

DOI 10.1016/j.celrep.2014.11.018PMC PMC4617309

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Abstract

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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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.
ORCID: Nomura, Daniel K.
Xu, Allison W.
Koliwad, Suneil K.
Venue: Cell Reports
Publisher: Elsevier BV
Published: 2014-12
Volume: 9
Issue: 6
Pages: 2124-2138
ISSN: 2211-1247 (ISSN-L)
DOI: 10.1016/j.celrep.2014.11.018
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: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by-nc-nd/3.0/ (vor)
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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Microglia dictate the impact of saturated fat consumption on hypothalamic inflammation and neuronal function.

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