Cristina Garcia Caceres
Institute for Diabetes and
Obesity at Helmholtz Munich, Germany
Medizinische Klinik and Poliklinik IV,
Klinikum der Universität, Ludwig-Maximilians-Universität München, Munich,
Germany
Title
Hunger Timing Influence by Hypothalamic Astrocytes
Abstract
Obesity is linked to compromised brain health, affecting food reward pathways, hormone-sensing neuronal activity, and brain connectivity. The arcuate nucleus (ARC) of the hypothalamus, a key hub for metabolic signals, traditionally thought to be regulated by neurons, is now known to involve astrocytes—non-neuronal cells that play a significant role in metabolic control. Unlike astrocytes in other brain regions, hypothalamic astrocytes respond uniquely to energy-dense food intake, modulating synaptic connectivity and influencing brain-peripheral communication. However, how the molecular mechanisms by which astrocytes regulate hunger circuits, remains unclear. In this talk, I will discuss ongoing studies focused on how astrocytes communicate with neighboring neurons in the ARC to regulate feeding. Using two-photon excitation imaging and electrophysiological recordings combined with genetically encoded fluorescence indicators, cell manipulation, and pharmacology in ex vivo brain slices from mouse models, we observe that the consumption of high-caloric meals boosts the calcium-dependent release of glutamate from astrocytes, which in turn increases the firing rate of AgRP/NPY neurons by activating NMDARs located at extrasynaptic sites. Furthermore, our data show that astrocyte calcium activity and the spontaneous firing rate of AgRP/NPY neurons exhibit similar daytime-linked activity patterns—i.e., low activity at the beginning of the day (fed state) and high activity just before the night cycle (non-satiated state). In sum, our findings suggest that glutamate-mediated astrocyte gliotransmission in the ARC could be a key mechanism governing the natural, temporal regulation of hunger, which may be altered under a hypercaloric diet, contributing to the hyperphagia associated with obesity.
Biosketch
Prof. Dr. Cristina Garcia Caceres earned her Ph.D. in Madrid, Spain, and completed academic internships at Yale University, USA, and Göteborg University, Sweden. After her doctoral studies, she conducted postdoctoral research at Helmholtz Munich and the Technical University of Munich in Germany. In 2015, she established the Astrocyte-Neuron Network Unit at the Institute for Diabetes and Obesity. Currently, she is a W2 Professor at Ludwig Maximilian University and serves as Head of Research and Deputy Director at the Institute for Diabetes and Obesity at Helmholtz Munich.
For over 16 years, Prof. Dr. Garcia Caceres has focused on understanding how the hypothalamus controls energy balance, particularly through astrocytes. Her research aims to uncover the cellular mechanisms underlying obesity and metabolic disorders. Her pioneering work, awarded with ERC Starting Grant, has shown that the brain's control of energy and glucose metabolism involves astrocytes. By exploring the interactions between neurons, astroglia, and blood vessels, she seeks insights to inform strategies for obesity prevention and treatment, including associated conditions like hypertension. Additionally, her recent research extends to understanding how the brain integrates peripheral endocrine cues into hypothalamic circuits, critical for metabolic adaptation in diet-induced obesity. Overall, her discoveries challenge traditional obesity treatment models and underscore the importance of considering sex as a biological variable in addressing this health issue.