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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Metabolic factors in the regulation of hypothalamic innate immune responses in obesity
Experimental & Molecular Medicine Open Access 26 April 2022
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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.).
The authors declare no competing interests.
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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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