The emerging role of astrocytes in the control of metabolism
Cristina García Caceres
Institute for Diabetes and Obesity, Helmholtz Zentrum Muenchen Neuherberg, Germany
Based on human GWAS and targeted mouse mutagenesis models, it has recently been revealed that obesity might be due to a disease of the brain, which could be a consequence of the brain misunderstanding the peripheral metabolic status in defense of body weight gain. One consequence of the lack of success in discovering and developing more efficacious, safe drugs for obesity might be represented by the fact that most research in the last decades was exclusively focused on exploring the functionality of neurons in the control of metabolism, while ignoring the presence and active role of glia cells such as astrocytes. Using specific transgenic mouse models for targeting metabolic receptors in astrocytes, we have demonstrated that hormone/nutrient signaling in astrocytes is determinant of the manner in which the brain senses whole-body metabolic demands (Garcia-Caceres et al., 2011; Kim et al., 2014; Gao et al., Diabetes 2017; Garcia-Caceres et al., 2016; García-Cáceres et al., 2019). Moreover ,our findings indicate that astrocytes respond to hypercaloric diets by developing a reactive phenotype -astrogliosis- in the hypothalamus (Horvath et al., 2010), which appears prior to significant diet-induced body weight gain, suggesting the potentially functional role of these glial cells in the pathogenesis of obesity. We are now proceeding by investigating whether hypothalamic astrocytes regulate diet-induced vascular remodeling within the hypothalamus, and if their hormone signaling and cellular metabolism are determinant of how astrocytes cooperate with neurons in the control of feeding behavior and glucose metabolism. Overall, our recent findings suggest a novel model in which astrocytes are actively involved at the intersection between neurons and the vasculature in the central nervous system control of systemic metabolism, and they may well be potential targets for improved pharmacological strategies to prevent and treat metabolic diseases.
Host: Amanda Sierra
This seminar is partially supported by the Campus of Biscay of the UPV/EHU.