AstroCOMET · Astrocyte-neuron COmmunication in METabolism and obesity.

Astrocyte-neuron COmmunication in METabolism and obesity.

Obesity and its associated comorbidities, such as type 2 diabetes, have become highly prevalent in our society and represent two major health threats for the future. Recent epidemiological data from the WHO showed that more than 1.9 billion adults aged 18 years and older are overweight and over 650 million adults are obese. Overall, about 13% of the world’s adult population (11% of men and 15% of women) is obese. The situation has reached epidemic proportions globally, with at least 2.8 million people dying each year as a result of being overweight or obese. This medical problem is the consequence of an energy imbalance between calories consumed and calories expended, but the fundamental pathophysiological causes leading to this imbalance are still not properly understood. In addition, despite decades of research, the development of safe and effective anti-obesity treatments has not been successful enough to correct the increasing presence of both maladies. The current state of the art, have identified the brain as the main regulator of systemic metabolism, suggesting that obesity has a brain-centered context. In particular, the hypothalamus acts as a center of the metabolic homeostasis by integrating constant inputs from circulating nutrients and endocrine signals and generating the appropriate physiological responses to maintain a balanced systemic metabolism and a stable body weight. While decades of investigations have resulted in major insights into how hypothalamic neurons govern feeding behavior and systemic metabolism, recent work suggests that the current model is constrained by the assumption that neurons are the only brain cell types involved in the central control of energy homeostasis. In particular, astrocytes, have recently been shown to be involved in the functional regulation of metabolism. For instance, high fat diet (HFD) induces metabolic and morphological disturbances in the hypothalamus including changes in its cytoarchitecture affecting how astrocytes interact physically with pro-opiomelanocortin (POMC) and neuropeptide Y (NPY) neurons in the hypothalamus – essential neuronal populations for the maintenance of energy homeostasis. Moreover, it has recently been reported that insulin receptors (IRs) in astrocytes were important players for the regulation of glucose homeostasis. Overall, together these results suggest a new paradigm in which astrocytes interplay with neurons for the CNS control of metabolism, body weight, and energy balance. However, the mechanisms by which astrocytes communicate with neurons to adjust the activity of feeding circuits and systemic metabolism in response to whole body energy demands remains to be investigated. Therefore, the overall objective of the AstroCOMET project was to study the role of hypothalamic astrocytes in the control of metabolism and how alterations in their function could be part of the obesity pathophysiology.

Data: CORDIS, © European Union