Astrocytic Process Plasticity and IKKβ/NF-κB in Central Control of Blood Glucose, Blood Pressure, and Body Weight

Publication date: 2 May 2017
Source:Cell Metabolism, Volume 25, Issue 5
Author(s): Yalin Zhang, Judith M. Reichel, Cheng Han, Juan Pablo Zuniga-Hertz, Dongsheng Cai
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.

Graphical abstract

Teaser

Zhang et al. report that astrocytes can actively respond to metabolic information such as fasting/refeeding and chronic overnutrition by dynamically changing their process length and density. Chronic overnutrition inflames astrocytes, thus impairing their plasticity and resulting in changes in extracellular neurotransmitter levels and downstream neuropeptides, which affect metabolism.


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