Physiological and pathophysiological roles of hypothalamic astrocytes in metabolism

The role of glial cells, including astrocytes, in metabolic control has received increasing attention in recent years. Although the original interest in these macroglial cells was a result of astrogliosis being observed in the hypothalamus of diet-induced obese subjects, studies have also focused on how they participate in the physiological control of appetite and energy expenditure. Astrocytes express receptors for numerous hormones, growth factors and neuropeptides. Some functions of astrocytes include transport of nutrients and hormones from the circulation to the brain, storage of glycogen, participation in glucose sensing, synaptic plasticity, uptake and metabolism of neurotransmitters, release of substances to modify neurotransmission, and cytokine production, amongst others. In the hypothalamus, these physiological glial functions impact on neuronal circuits that control systemic metabolism to modify their outputs. The initial response of astrocytes to poor dietary habits and obesity involves activation of neuroprotective mechanisms but, with chronic exposure to these situations, hypothalamic astrocytes participate in the development of some of the damaging secondary effects. The present review discusses not only some of the physiological functions of hypothalamic astrocytes in metabolism, but also their role in the secondary complications of obesity, such as insulin resistance and cardiovascular affectations.