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Tanycytic structural plasticity in circumventricular organs underlies homeostatic brain-body communication

Principal Investigator:
  • Masha Prager-Khoutorsky,

    McGill University

  • The Azrieli Foundation

Project Overview

Metabolic syndrome is a group of risk factors (obesity, hypertension, high fasting blood sugar, and high levels of triglycerides) that increase the risk of type 2 diabetes and cardiovascular diseases. Over 20% of adult Canadians suffer from metabolic syndrome (40% in adults over 60 years old), and effective treatments are lacking. Disruptions in brain-to-body communication significantly contributes to metabolic syndrome.

The brain is isolated from peripheral blood circulation by a barrier that protects it from the entrance of harmful substances. However, a few specialized brain areas located in the hypothalamus are not fully isolated from peripheral circulation and thus can sense the composition of the blood (e.g. levels of glucose and hormones). These specialized brain areas are of key importance for the organism, as they respond to the levels of circulating molecules by controlling vital functions, such as food intake and energy metabolism. Failure to sense the composition of the blood (glucose and hormones) by these areas leads to the development of obesity, metabolic syndrome, and type 2 diabetes.

The proposed project aims to study the mechanisms regulating properties of the barrier in rodents and examine if barrier properties vary between fasting and fed animals. Further, we will test if this barrier malfunctions in animals fed high fat/glucose diet, preventing circulating satiety molecules from entering the brain, leading to the unresponsiveness of the brain to satiety signals, and contributing to the development of obesity and type II diabetes.

The proposed research will increase our understanding of how the brain regulates metabolic and hormonal balance and how disruption of this regulation contributes to pathologies such as obesity and type 2 diabetes. This work is expected to have a strong impact on the design of therapies to alleviate these disorders.