Astrocytes in energy homeostasis
Astrocytes are a widespread type of glial cell in the central nervous system (CNS), and have a key role in the regulation of metabolic homeostasis and neurotransmission, as well as a supportive role in the structure and metabolism of neurons. Food intake is a major part of energy homeostasis across the whole body, and has a key impact on the development of diet-induced obesity and its associated comorbidities - including type 2 diabetes and cardiovascular disease. Understanding the mechanisms behind food intake and energy homeostasis in the CNS could help us develop new interventions in the progression of obesity.
Before being based at Exeter, Dr. Kate Ellacott’s group were among the first to characterise the response of astrocytes to diet induced and genetic obesity in mice (Buckman et al 2013, JCN). In addition they provided the demonstration that genetic manipulation of inflammatory signalling in astrocytes modulates food intake in mice (Buckman et al 2015, Molecular Metabolism). Subsequent work in Exeter has focused on investigating how astrocytes embedded in specific feeding circuits in the hypothalamus and brainstem communicate with local neurons and manipulate food intake. To answer these questions we are using electrophysiology, chemogenetics, immunohistochemistry and behavioural assays. Recently we showed that astrocytes in the brainstem respond to increased food intake and that selective activation of these cells reduced food intake in mice (MacDonald et al 2020, Glia).
Publications
MacDonald AJ, Ellacott KLJ. Astrocytes in the Nucleus of the Solitary Tract: Contributions to Neural Circuits Controlling Physiology. Physiology & Behaviour. 2020 Jun;112982.doi:10.1016/j.physbeh.2020.112982
MacDonald AJ, Holmes FE, Beall C, Pickering AE, Ellacott KLJ. Regulation of food intake by astrocytes in the brainstem dorsal vagal complex. Glia. 2020 Jun;68(6):1241-1254. doi: 10.1002/glia.23774.
Buckman LB, Thompson MM, Lippert RN, Blackwell TS, Yull FE, Ellacott KL. Evidence for a novel functional role of astrocytes in the acute homeostatic response to high-fat diet intake in mice. Mol Metab. 2014 Oct 16;4(1):58-63. doi: 10.1016/j.molmet.2014.10.001.
Buckman LB, Thompson MM, Moreno HN, Ellacott KL. Regional astrogliosis in the mouse hypothalamus in response to obesity. J Comp Neurol. 2013 Apr 15;521(6):1322-33. doi: 10.1002/cne.23233.