Research Description
Obesity and type 2 diabetes (T2D) exerts an enormous economic burden on the healthcare world-wide. Extensive efforts have been dedicated to elucidating the various causes affecting the development of obesity/T2D. Gender-specific differences have been reported in the development and treatment of these diseases. Within the brain, the hypothalamus plays a crucial role in the modulation of energy metabolism and has been causally linked to the development of obesity/T2D. Hypothalamic neurons maintain constant reciprocal communication with astrocytes. Astrocytes have gained particular attention for their close involvement in the development of inflammation and metabolic disorders. The role and mechanisms via which astrocytes modulate brain adaptations to high-dense caloric diet in a sex-manner are poorly understood. The overall goal of this proposal is to understand the pathological changes in astrocyte function in the hypothalamus in response to a high-caloric diet and if this is regulated differentially between sexes. We will use cutting edge animal models and viral vector technologies to specifically target astrocyte function in the hypothalamus to evaluate astrocyte mechanisms involved in the development of obesity/T2D. Our results will provide evidence of the involvement of mal-adaptations in astrocyte-neuron communication in the onset of obesity/T2D and may be useful to identify novel therapeutic targets to help manage obesity/T2D and associated pathologies.Research Profile
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?Obesity is a significant public health problem associated with an increased risk of developing type 2 diabetes (T2D). Over the past 20 years, the brain has been identified as a major contributor in the development to obesity/T2D. Our aim is to increase fundamental knowledge about the brain mechanisms involved in obesity/T2D. The findings from experiments described in the present proposal will impact the field of diabetes at the academic and pre-clinical level by highlighting the crucial role of hypothalamic astrocytes in the development of diabetes and will provide innovative alternative targets for treating or preventing diabetes.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?Over 90% of individuals with T2D are either overweight or obese. Over time, T2D leads to detrimental consequences on e.g. the recovery of cardiovascular diseases and viral infections, such as COVID-19. Adaptation to a high-caloric environment and the development of metabolic alterations are highly dependent on the sex and gender of the individual. My research will shed light on the brain mechanisms and important modulating factors that affect the development of T2D in a sex-dependent manner. The information obtained from our results will help shaping prevention and potential treatment targets to reverse T2D.
Why important for you, personally, to become involved in diabetes research? What role will this award play?During my career progression, I have been interested in understanding how the brain modulates systemic metabolism. My work has directly contributed to the diabetes field by showing that the brain is an essential metabolic hub for physiological systemic glucose metabolism, and that derangements in the brain can result in development of metabolic diseases. Being awarded with the diabetes research grant will have a remarkable impact on my scientific development, allowing me to further expand on my interest in diabetes research in a multidisciplinary scientific environment. Moreover, this award will allow me to communicate my research efforts and societal implications to the general public by presenting on international conferences.
In what direction do you see the future of diabetes research going?To dampen the obesity/T2D epidemic, effective prevention strategies are crucial. As T2D is a multifactorial disease involving a complex interaction between molecular, cellular and physiologic alterations, extensive efforts are being dedicated to elucidating the various factors affecting the development of the disease. Understanding the complex pathology of obesity/T2D and which aspects differentially affect women and men will be critical in shaping effective preventive and therapeutic measures. I believe that the field will be focusing in individualized or precision medicine to target individual-specific pathophysiological mechanisms.