Obesity and Hypertension: Researchers Discover Novel Mechanisms
Researchers have succeeded for the first time in demonstrating the role of hypothalamic astrocytes in obesity-related hypertension. In addition, they showed that the hormone leptin is involved in the increase of blood vessels in the hypothalamus of obese mice, contributing of hypertension. Helmholtz Zentrum München led the study and collaborated with Ludwig-Maximilians-Universität München, the Technical University of Munich and the German Diabetes Center.
Hypertension is a widespread comorbidity of patients with obesity that greatly increases the risk of mortality and disability. In recent years, researchers have found that a high-calorie diet increases the density of blood vessels (hypervascularization) in the hypothalamus – an important “eating control” area in our brain. Researchers hypothesized that elevated hormone levels of leptin are associated with a higher risk of developing hypertension. However, the exact mechanisms that contribute to the condensed growth of blood vessels in the hypothalamus were unknown.
New research conducted by Cristina García-Cáceres' research group at Helmholtz Zentrum München has now revealed that obese mice do not increase the amount of blood vessels in the hypothalamus when they lack the hormone leptin. Leptin is produced by adipose tissue, is involved in the control of hunger and satiety, and plays an important role in the regulation of fat metabolism in humans and mammals.
Once the researchers increased the hormone leptin in these mice, certain brain cells, the astrocytes, boosted the production of a specific growth factor. This growth factor, in turn, promoted vessel growth. The result was an increased number of vessels in the hypothalamus (and no other brain region). The scientists thus demonstrated that leptin is mainly responsible for the increased concentration of vessels in the hypothalamus and that this process is mediated via astrocytes.
“We provide a paradigm shift in our understanding of how the hypothalamus controls blood pressure in obesity,” explains first author Tim Gruber. “While previous research has focused primarily on neurons, our research highlights the new role of astrocytes, historically assumed less relevant than neurons, in controlling blood pressure”.
Looking into the future, according to study leader Cristina García-Cáceres, one important question remains: How exactly do astrocytes communicate with neurons? “We have started to answer this question using in vivo real-time imaging of astrocyte-neuron circuit function in the hypothalamus,” the researcher says.
Gruber et al., 2021: Obesity-associated hyperleptinemia alters the gliovascular interface of the hypothalamus to promote hypertension. Nature Metabolism, DOI: 10.1016/j.cmet.2021.04.007
Research highlight article in Nature Reviews Endocrinology: https://www.nature.com/articles/s41574-021-00511-3
Helmholtz Zentrum München
The Helmholtz Zentrum München, the German Research Center for Environmental Health, pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes, allergies and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München is headquartered in Neuherberg in the north of Munich and has about 2,300 staff members. It 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. www.helmholtz-muenchen.de/en