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ERC Starting Grant for Metabolism Research on Brain Cells

Over the next five years, the European Research Council (ERC) is funding the "AstroNeuroCrosstalk" project at Helmholtz Zentrum München with an ERC starting grant worth 1.5 million euros. In this context, Dr. Cristina García-Cáceres and her team are investigating how brain cells called astrocytes cooperate with neurons in the control of systemic metabolism in response to hormones and nutrients.

Dr. Cristina García-Cáceres. Source: Helmholtz Zentrum München

Despite vigorous prevention and treatment efforts, the prevalence of obesity and type 2 diabetes has increased dramatically around the world in recent decades. “Given the need to develop safe and effective anti-obesity drugs, the scientific community must step up its efforts to improve our understanding of the mechanisms involved in the development of obesity,” Dr. Cristina García-Cáceres says, describing what drives her. She heads the Astrocyte Biology Unit at the Institute for Diabetes and Obesity of Helmholtz Zentrum München.

Although astrocytes are the most abundant cells in the brain, they have been considered until recently less relevant than neurons in the control of metabolism. However, the processes of these characteristic star-shaped cells form the membrane interface between the brain surface and blood vessels - a privilege position for controlling the accessibility of blood-borne metabolic signals within the brain.

By this reason García-Cáceres’ work focuses on discerning the functional role of these cells in the central nervous system (CNS) control of metabolism. Together with colleagues, she reported in the renowned journal ‘Cell’ that astrocytes, which had previously been described only as supportive cells, mediate glucose transport in the brain by insulin signaling. Moreover, other publications by the neurobiologist and her team demonstrated that a high-fat, high-sugar diet induces alterations in the cyto-architecture of the hypothalamus including changes in physical interactions between astrocytes and neurons and blood vessels. Likewise astrocytes in respond to such hypercaloric diets develop a reactive phenotype known as astrogliosis* in the hypothalamus before any changes occur in body weight gain or systemic inflammation, which suggests a potential role of astrocytes in the pathogenesis of obesity.

“Until now, the role of astrocytes in energy metabolism was ignored, yet we have recently demonstrated that astrocytes are able to respond to nutrients and hormones, and in turn participate together with neurons in the control of metabolism,” García-Cáceres says. “We now take advantage of using new technology targeting non-neuronal cells to develop a functional understanding of the astroglia-network in the CNS for the control of body weight and energy metabolism in health and metabolic disease”.

She now wants to pursue this hypothesis in the framework of the funded “AstroNeuroCrosstalk” project, which the European Research Council (ERC) will support with a 1.5 million euro grant over the next five years. Specifically, she wants to unravel if astrocytes communicate with neurons for controlling body weight, food intake and energy expenditure and if such communication might be affected by the consumption of hypercaloric diets contributing to the development of obesity and type 2 diabetes.

García-Cáceres hopes the findings could lead to new treatment strategies in the long term: “Our studies aim to uncover the molecular basis of astrocyte-neuron communication in the metabolic context with a view to developing new therapeutic strategies to combat diabetes and obesity.”

Further Information

* Astrogliosis is a reactive process leading to cellular, molecular, and functional changes in astrocytes including a hypertrophy associated with an increase in astrocytic proteins such as GFAP and vimentin, and it occurs in brain injuries reflecting healing processes or pathophysiology.

As German Research Center for Environmental Health, Helmholtz Zentrum München pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes mellitus, allergies and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München has about 2,300 staff members and is headquartered in Neuherberg in the north of Munich. Helmholtz Zentrum München is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 37,000 staff members. 

The Institute of Diabetes and Obesity (IDO) studies the diseases of the metabolic syndrome by means of systems biological and translational approaches on the basis of cellular systems, genetically modified mouse models and clinical intervention studies. It seeks to discover new signaling pathways in order to develop innovative therapeutic approaches for the personalized prevention and treatment of obesity, diabetes and their concomitant diseases. IDO is part of the Helmholtz Diabetes Center (HDC).