Hypothalamic microglia as potential regulators of metabolic physiology.
Abstract
Tissue-resident myeloid cells initiate local inflammation in response to infectious or injurious stimuli. Sixteen years ago, macrophages in the adipose tissue (ATMs) were shown to undergo a form of activation in response to diet-induced obesity, thus leading to the conclusion that these macrophages sense a type of pro-inflammatory injury. ATMs are now known to be central to adipose tissue development, plasticity, maintenance and function. Indeed, their involvement in obesity may represent hijacking of these functions. More recently, microglia, 'CNS macrophages', have been shown to accumulate and undergo activation in response to dietary excess in the mediobasal hypothalamus (MBH), and early studies have implicated these cells as injury-responsive mediators of hypothalamic dysfunction. However, microglia are amazingly diverse cells now known to have moment-to-moment sensory functions and to communicate with neighbouring neurons to maintain and shape brain circuitry. Here, we build on this view, detailing our rapidly evolving understanding of microglial heterogeneity in the MBH and their roles as nutrient and environmental sensors. We propose that microglia, instead of simply responding to diet-induced damage, act as critical metabolic regulators that may coordinate a complex cellular network in the MBH. Understanding their roles in hypothalamic development and function should reveal unexpected mechanistic information relevant to important diseases such as obesity.
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An appropriate level of microglia activity within the hypothalamus is necessary to maintain proper control of energy balance.
“Our data contribute to the growing concept that an appropriate level of microglia activity within the hypothalamus is necessary to maintain proper control of energy balance (Valdearcos 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., 2019
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“In the context of this study, it is possible that the deletion of the Abi3 gene locus impaired the ability of microglia to perform the complex functions that are necessary to regulate energy balance (Valdearcos et al., 2019; De Luca et al., 2020).”
Background
- Authors
- Valdearcos, M., Myers, M. G., & Koliwad, S. K.
- Affiliations
- University of Michigan (US)
- University of California, San Francisco (US)
- Corresponding author
- Koliwad, Suneil K.
- Venue
- Nature Metabolism
- Published
- 2019-03-04
- Volume
- 1
- Issue
- 3
- Pages
- 314-320
- ISSN
- 2522-5812 (ISSN-L)
- OpenAlex
- W2920179644
- Cited by
- 52
- References
- 13
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 12 · 2023: 6 · 2022: 16 · 2021: 4 · 2020: 3 · 2019: 4
- FWCI
- 0.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK056731)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- mediobasal hypothalamus, microglial heterogeneity, microglial activation, obesity, diet-induced obesity, nutrient sensing, environmental sensing, hypothalamic dysfunction, adipose tissue macrophages, myeloid cells, metabolic regulation, overnutrition
- MeSH terms
- Adipose Tissue, Animals, Diet, Energy Metabolism, Humans, Hypothalamus, Macrophages, Microglia, Myeloid Cells
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