Cell Metabolism
Volume 25, Issue 5, 2 May 2017, Pages 1091-1102.e4
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Article
Astrocytic Process Plasticity and IKKβ/NF-κB in Central Control of Blood Glucose, Blood Pressure, and Body Weight

https://doi.org/10.1016/j.cmet.2017.04.002Get rights and content
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Highlights

  • Astrocytic process plasticity is vital for the central control of metabolic balance

  • Astrocytes control extracellular neurotransmitter level to regulate metabolic balance

  • Astrocytic plasticity is impaired by chronic overnutrition or metabolic inflammation

  • Inflamed astrocytes lead to metabolic imbalance and thus metabolic syndrome

Summary

Central regulation of metabolic physiology is mediated critically through neuronal functions; however, whether astrocytes are also essential remains unclear. Here we show that the high-order processes of astrocytes in the mediobasal hypothalamus displayed shortening in fasting and elongation in fed status. Chronic overnutrition and astrocytic IKKβ/NF-κB upregulation similarly impaired astrocytic plasticity, leading to sustained shortening of high-order processes. In physiology, astrocytic IKKβ/NF-κB upregulation resulted in early-onset effects, including glucose intolerance and blood pressure rise, and late-onset effects, including body weight and fat gain. Appropriate inhibition in astrocytic IKKβ/NF-κB protected against chronic overnutrition impairing astrocytic plasticity and these physiological functions. Mechanistically, astrocytic regulation of hypothalamic extracellular GABA level and therefore BDNF expression were found partly accountable. Hence, astrocytic process plasticity and IKKβ/NF-κB play significant roles in central control of blood glucose, blood pressure, and body weight as well as the central induction of these physiological disorders leading to disease.

Keywords

astrocyte
hypothalamus
IKKβ
NF-κB
inflammation
blood glucose
blood pressure
obesity
diabetes
hypertension

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