Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Role of Hypothalamic Reactive Astrocytes in Diet-Induced Obesity

  • Sa, Moonsun (KU-KIST Graduate School of Converging Science and Technology, Korea University) ;
  • Park, Mingu Gordon (KU-KIST Graduate School of Converging Science and Technology, Korea University) ;
  • Lee, C. Justin (KU-KIST Graduate School of Converging Science and Technology, Korea University)
  • Received : 2021.11.14
  • Accepted : 2022.01.12
  • Published : 2022.02.28
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Abstract

Hypothalamus is a brain region that controls food intake and energy expenditure while sensing signals that convey information about energy status. Within the hypothalamus, molecularly and functionally distinct neurons work in concert under physiological conditions. However, under pathological conditions such as in diet-induced obesity (DIO) model, these neurons show dysfunctional firing patterns and distorted regulation by neurotransmitters and neurohormones. Concurrently, resident glial cells including astrocytes dramatically transform into reactive states. In particular, it has been reported that reactive astrogliosis is observed in the hypothalamus, along with various neuroinflammatory signals. However, how the reactive astrocytes control and modulate DIO by influencing neighboring neurons is not well understood. Recently, new lines of evidence have emerged indicating that these reactive astrocytes directly contribute to the pathology of obesity by synthesizing and tonically releasing the major inhibitory transmitter GABA. The released GABA strongly inhibits the neighboring neurons that control energy expenditure. These surprising findings shed light on the interplay between reactive astrocytes and neighboring neurons in the hypothalamus. This review summarizes recent discoveries related to the functions of hypothalamic reactive astrocytes in obesity and raises new potential therapeutic targets against obesity.

Keywords

Acknowledgement

This work was supported by the Institute for Basic Science (IBS), Center for Cognition and Sociality (IBS-R001-D2), and Global Ph.D. Fellowship programs (2017H1A2A1042357) of the NRF of Korea.

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