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Hypothalamic microglia as potential regulators of metabolic physiology

Nature Metabolism volume 1, pages 314–320 (2019)Cite this article

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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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Fig. 1: CNS myeloid cell types as environmental sensors and key regulators of hypothalamic metabolic control.

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Acknowledgements

The authors thank members of their respective laboratories for helpful discussions on the topic. This work was funded by the NIDDK (R01DK056731 to M.G.M., K01DK113064 to M.V. and R01DK098722 to S.K.K.).

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Authors and Affiliations

  1. Diabetes Center, University of California San Francisco, San Francisco, CA, USA

    Martin Valdearcos & Suneil K. Koliwad

  2. Department of Medicine, University of California San Francisco, San Francisco, CA, USA

    Martin Valdearcos & Suneil K. Koliwad

  3. Department of Internal Medicine and Graduate Program in Cellular and Molecular Biology, University of Michigan Medical School, Ann Arbor, MI, USA

    Martin G. Myers Jr

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Correspondence to Suneil K. Koliwad.

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Valdearcos, M., Myers, M.G. & Koliwad, S.K. Hypothalamic microglia as potential regulators of metabolic physiology. Nat Metab 1, 314–320 (2019). https://doi.org/10.1038/s42255-019-0040-0

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