Seminar

The emerging role of hypothalamic astrocytes in the regulation of energy balance

Luis Varela

Hypothalamic astrocytes play pivotal roles in both nutrient sensing and the modulation of synaptic plasticity of hypothalamic neuronal circuits in control of feeding and systemic glucose and energy metabolism. Here, we show the relevance of astrocytic fatty acid (FA) homeostasis under the opposing control of angiopoietin-like 4 (ANGPTL-4) and peroxisome proliferator-activated receptor gamma (PPAR) in the cellular adaptations of hypothalamic astrocytes and neurons to the changing metabolic milieu. We observed that increased availability of FA in astrocytes induced by cell- and time-selective knock down of Angptl4 protected against diet-induced obesity, while cell- and time-selective knock down of Angptl4-regulated Ppar lead to elevated susceptibility to obesity. Overall, our results unravel a novel role for astrocytic FA metabolism in central control of body weight and glucose homeostasis. On the other hand, I have also found a mechanism by which ghrelin modulates astrocyte activity. I discovered that the effects of this hormone on hypothalamic astrocytes are not direct, but mediated through AgRP neurons. During its activation, AgRP neurons release GABA, that signals to neighboring astrocytes modulating their function.