ArticleActa neuropathologica2016
High-fat diet-induced brain region-specific phenotypic spectrum of CNS resident microglia.
Article in Acta neuropathologica, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 144 papers, 1 of them a synthesis that pooled it.
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Who cites it
144 citing papers in PubMed, 1 synthesis or guideline pooled it, 228 citations in OpenAlex.
- Effects of diabetes on microglial physiology: a systematic review of in vitro, preclinical and clinical studies.Journal of neuroinflammation · 2023Pooled it
- High-fat diet intake induces neuroinflammation and alters the dopaminergic system in the amygdala of juvenile rats.Brain, behavior, & immunity - health · 2026Article
- Weight loss aggravates obesity-induced hypothalamic inflammation in mid-aged mice.GeroScience · 2026Article
- Restriction spectrum imaging reveals brain microstructural correlates of obesity risk in early childhood.Scientific reports · 2026Article
- Ovarian hormones and high-fat diet duration distinctively modulate hypothalamic chemokine profile.Journal of neuroendocrinology · 2026Article
- Redefining the timeline: a three-phase framework of hypothalamic microinflammation in metabolic disease.Reviews in endocrine & metabolic disorders · 2026Review
- L-Alliin Modulates Brain Region-Specific Neuroinflammatory Responses to Lipopolysaccharide in Diet-Induced Obese Mice.Brain sciences · 2026Article
- Neuroendocrine-immune perturbations in metabolic disease: pathophysiological mechanisms underlying cognitive impairment.Frontiers in human neuroscience · 2026Review
- Loss of ovarian hormones is detrimental in early disease stages of mouse models of Alzheimer's disease and multi-etiology dementia.Biology of sex differences · 2025Article
- TNF as a mediator of metabolic inflammation and body-brain interaction in obesity-driven neuroinflammation and neurodegeneration.Ageing research reviews · 2025Review
- A role for microglia in mediating the microbiota-gut-brain axis.Nature reviews. Immunology · 2025Review
- Exploring the Impact of a High-Fat Diet on Brain Homeostasis: A Comprehensive Analysis of the Absence of Inflammation.Molecular nutrition & food research · 2025Article
- Microglia/macrophage-specific deletion of TLR-4 protects against neural effects of diet-induced obesity in a sexually dimorphic manner.Journal of neuroinflammation · 2025Article
- Neurobiochemical Effects of a High-Fat Diet: Implications for the Pathogenesis of Neurodegenerative Diseases.Biology · 2025Review
- High-Fat Diet-Induced Excessive Accumulation of Cerebral Cholesterol Esters and Microglial Dysfunction Exacerbate Alzheimer's Disease Pathology in APPMolecular neurobiology · 2025Article
- Article
- AMPK as a Therapeutic Target: Advancing Epilepsy Management Through Metabolic Modulation.Molecular neurobiology · 2025Review
- White matter microstructure in obesity and bipolar disorders: an ENIGMA bipolar disorder working group study in 2186 individuals.Molecular psychiatry · 2025Article
- Interactions between menopause and high-fat diet on cognition and pathology in a mouse model of Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Sex-dependent effects of a high-fat diet on the hypothalamic response in mice.Biology of sex differences · 2025Article
84 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diets high in fat (HFD) are known to cause an immune response in the periphery as well as the central nervous system. In peripheral adipose tissue, this immune response is primarily mediated by macrophages that are recruited to the tissue. Similarly, reactivity of microglia, the innate immune cells of the brain, has been shown to occur in the hypothalamus of mice fed a high-fat diet. To characterize the nature of the microglial response to diets high in fat in a temporal fashion, we studied the phenotypic spectrum of hypothalamic microglia of mice fed high-fat diet for 3 days and 8 weeks by assessing their tissue reaction and inflammatory signature. While we observed a significant increase in Iba1+ myeloid cells and a reaction of GFAP+ astrocytes in the hypothalamus after 8 weeks of HFD feeding, we found the hypothalamic myeloid cell reaction to be limited to endogenous microglia and not mediated by infiltrating myeloid cells. Moreover, obese humans were found to present with signs of hypothalamic gliosis and exacerbated microglia dystrophy, suggesting a targeted microglia response to diet in humans as well. Notably, the glial reaction occurring in the mouse hypothalamus was not accompanied by an increase in pro-inflammatory cytokines, but rather by an anti-inflammatory reaction. Gene expression analyses of isolated microglia not only confirmed this observation, but also revealed a downregulation of microglia genes important for sensing signals in the microenvironment. Finally, we demonstrate that long-term exposure of microglia to HFD in vivo does not impair the cell's ability to respond to additional stimuli, like lipopolysaccharide. Taken together, our findings support the notion that microglia react to diets high in fat in a region-specific manner in rodents as well as in humans; however, this response changes over time as it is not exclusively pro-inflammatory nor does exposure to HFD prime microglia in the hypothalamus.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.