07:38am Saturday 06 June 2020

Researchers describe a new brain signalling pathway that regulates body weight


Thyroid hormones regulate the lipid synthesis in the liver through a hypothalamus-coordinated pathway in the brain, according to an article published in the journal Cell Metabolism, which counts with the participation of the researchers Francesc Villarroya and Joan Villarroya, from the Faculty of Biology and the Institute of Biomedicine of the University of Barcelona (IBUB). The new study describes for the first time the molecular mechanism that regulates the lipid metabolism in the liver with brain signals and opens new horizons to the therapy design to treat obesity and other metabolic diseases.


Losing weight without dieting

This study, led by Miguel López, Noelia Martínez and Patrícia Seoane, from the group NeurObesidad of the University of Santiago de Compostela, analyses action mechanisms in thyroid hormones in the brain, on genetically altered mice. In particular, these mice do not present the AMP-activated protein kinase (AMPK) in the hypothalamic neurons. This protein, which takes part in the first stages of the lipid production, is highly sensitive to changes in the cell energy metabolism. According to the results, these mice had a lower body weight –compared to the group of control mice- without reducing their food intake.

According to Professor Francesc Villarroya, member of the Physiopathology of Obesity and Nutrition Networking Biomedical Research Center (CIBERobn) of the Institute of Health Carlos III, “It’s been a while we knew thyroid hormones activated the synthesis of fat in the liver. This was quite hard to understand since thyroid hormones generally tend to ‘burn’ metabolic substratum instead of increasing its synthesis. The new study states for the first time that this fat synthesis –destined to be ‘burned’ in the brown adipose tissue- results from an action coordinated in the hypothalamus, an area of the brain that regulates the energy of the body.

Thyroid hormones act in the hypothalamus modulating several molecular pathways, the most important being regulated by AMPK protein. In this study, the scientific team stated that thyroid hormones are capable of inhibiting the function of the AMPK protein in a specific population of hypothalamic neurons, something which ends up activating two regulating molecular pathways of the brown fat and liver function. The UB experts, members of the Research Group on Genetics and Molecular Biology of Mitochondrial Proteins and Associated Diseases, participated in the identification and characterization of brown adipose tissue activation processes in response to the thyroid hormone brain action.

New chances in the design of future therapies

Thyroid hormones can also act directly on tissues, without having to passing through the brain. The new study could open future windows for the treatment of metabolic diseases such as obesity. In particular, the new coordinating “brain” pathway between the liver and the brown adipose tissue could be pharmacologically activated with analogues and molecules without having to point up to outlying effects.

“In theory, the features of the thyroid hormones –boosting energy expenditure and producing body heat out of the fats or thermogenesis- are of great interest to treat obesity” says Francesc Villarroya.  “However, tyroid hormone levels cannot be increased for therapeutic aims. It’s true they help lose weight but they have many adverse effects which should be looked at”.

Identifying tools to modulate the main brain action mediating signals in thyroid hormones, and boosting energy expenditure avoiding side effects are some of the options to be researched on after this new study. In the future, researchers could explore new pharmacological modulation strategies on pathologies that occur with fatty liver (hepatic steatosis).

This interdisciplinary study counted with the participation of Adipoplast  (network of excellence of adipose plasticity and its pathologies) of the Ministry of Economy, Industry and Competitiveness (MINECO), led by Professor Francesc Villarroya and unifying nucleus of many signing teams in the new article.

Universitat de Barcelona


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