A team led by Professor Manuel Vázquez-Carrera, researcher from IBUB of Faculty of Pharmacy and Food Sciences (UB), has conducted a review study on the Growth Differentiation Factor 15 (GDF15) —a protein expressed under physiological stress conditions— and its potential impact on the treatment for type 2 diabetes. The study, published in the journal Trends in Endocrinology and Metabolism, gathers the most recent research studies on the functioning of this cytokine, which consolidate it as a potential therapeutic target against this disease.
“This review gathers the latest novelties on the metabolic effects of GDF15 in the context of type 2 diabetes, which are an important turn of what we knew to date. The findings in animal models are specially encouraging and they show that GDF15-based therapies are promising for the treatment of this disease, although we need more clinical studies on humans to confirm it”, notes Manuel Vázquez-Carrera, also researcher at the Research Institute Sant Joan de Déu (IRSJD) and at the Biomedical Research Networking Center in Diabetes and Associated Metabolic Disorders (CIBERDEM).
Benefitial effects on the metabolism
Type 2 diabetes is a complex metabolic disease characterized mainly by an excessive amount of glucose in the blood due to the body’s inability to produce insulin or to use it in the wrong way. In situations of intracellular organelle stress such as the ones caused by this and other diseases, the cells secrete stress-sensitive cytokines such as GDF15, which activate mechanisms to counteract processes like inflammation or insulin resistance.
Recent studies have shown that these beneficial effects on the metabolism are produced through the activation of the GFRAL receptor in the brain: once it is activated, the intake is reduced and, as a result, there is weight loss, which would reduce the obesity and would improve associated diseases such as type 2 diabetes. However, new evidence gathered in this review show that GDF15 can have effects mediated by other peripheral receptors that contribute to improve metabolic diseases.
“To date, it was thought that the GDF15 effects were mediated exclusively by this GFRAL central receptor with an expression restricted to the neurons in the postrema area and the nucleus of the solitary tract, areas of the brain that are involved in the control of hunger and regulation of body weight”, notes the researcher. “Now, it has been shown that the GDF15 has beneficial effects such as the increase in thermogenesis, lipid catabolism and mitochondrial oxidative phosphorylation regardless of the changes in the food intake, which suggests that the GDF15 could also exert its effects through receptors other than GFRAL and independently of the reduction in hunger.
According to the researchers, the discovery of the potential peripheral receptors responsible for this metabolic effects of GDF15 can “help to better understand how this stress cytokine works and to facilitate its pharmacological modulation”.
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Reference article:
Aguilar-Recarte, D.; Emma Barroso, E.; Palomer, X.; Wahli, W.; Vázquez-Carrera, M. «Knocking on GDF15’s door for the treatment of type 2 diabetes mellitus». Trends in Endocrinology and Metabolism, September 2022. DOI: https://doi.org/10.1016/j.tem.2022.08.004
