Graphical abstraction. Credit: DOI: 10.1016 / j.celrep.2021.109501
Studies published in the journal Cell report Describes new pathways associated with receptor activity associated with several metabolic or cardiovascular diseases such as diabetes, obesity, and hypertension. In conclusion, many of the anti-diabetic effects of PPARβ / δ receptor activators, which are potential therapeutic targets for the treatment of type 2 diabetes, are cytokines, proteins that are expressed under physiological stress conditions. Adjusted by GDF15.
The study has contributed to the discovery of new therapeutic pathways for the treatment of metabolic dysfunction, led by Professor Manuel Vázquez-Carrera of the Faculty of Pharmaceutical Sciences and Food Sciences at the University of Barcelona Institute of Biomedical Sciences (IBUB). SantJoande Déu (IRSJD) and Center for Networking Biomedical Research on Diabetes and Related Metabolic Diseases (CIBERDEM).
Cytokine GDF15, a factor that regulates energy metabolism
PPAR (Peroxisome proliferator activation) Receptor) Is a transcription factor of the superfamily of hormone nuclear receptors. Dysfunction of these receptors is associated with some metabolic or cardiovascular pathologies that have a high incidence in the population.
Papers published in Cell report We confirm that many anti-diabetic effects of PPARβ / δ activators act via the cytokine GDF15. This is more important than the activation of the GFRAL neuron receptor, the most well-known pathway to date. New regulatory pathways function through activation of the AMPK protein, a sensor of intracellular energy metabolism.
“GDF15 or growth differentiation factor 15 is a stress-responsive cytokine that is elevated in many diseases such as heart failure and cancer. Fatty liverEtc.) — Proposed as potential biomarkers for many diseases, ”says Manuel Basquez Carrera, a professor of pharmacology, toxicology, and therapeutic chemistry.
This cytokine is expressed in numerous cells, tissues and organs (liver, skeletal muscle, adipose tissue, kidneys, heart, placenta, macrophages, etc.). Its expression is increased under the conditions of organelle stress (mitochondrial stress or endoplasmic reticulum stress) and environmental factors (nutrient excess).
“Recent studies have shown that the cytokine GDF15 has a beneficial effect on metabolism through activation of GFRAL receptors in the brain. When GFRAL receptors are activated, intake is reduced and As a result, they lose weight and can lose weight. They are obese and will improve related illnesses such as type 2 diabetes, “said Vázquez-Carrera.
AMPK activation pathway mediated by cytokine GDF15
This study shows how GDF15-mediated activation of AMPK increases GDF15 levels. This increases the activation of the same AMPK in skeletal muscle and randomly increases GFRAL receptors in the brain.
“We believe this pathway is a positive feedback system that sustains AMPK activation,” says Vázquez-Carrera. “Therefore, the cytokine GDF15 exhibits peripheral as well as central effects.”
Specifically, AMPK is activated in situations characterized by low levels of cellular energy and glucose. When activated, AMPK initiates a series of catabolic processes (degradation) that produce ATP (a molecule that carries chemical energy) and at the same time inhibits the anabolic process (synthesis) that receives ATP.
“AMPK is an important regulator of many processes involved in cellular energy metabolism, including increased glucose uptake and fatty acid oxidation, increased mitochondrial oxidative capacity, and improved insulin resistance, so this activation mechanism. Is important. ” researcher.
New therapeutic targets to combat metabolic disorders
The GDF15-mediated pathway of AMPK activation is an important mechanism for type 2 diabetes. “Currently, there are several drugs that activate AMPK, which are considered safe drugs. The potential effects this may have on GDF15-mediated activation of GFRAL are still unknown. Overstimulation This neuroreceptor The effects of the body can be accompanied by the appearance of adverse effects that we should consider, “the researchers say.
“In this regard, high levels of GDF15 produced in cancer and subsequent activation of GFRAL are the mechanisms responsible for the appearance of cachexia associated with the disease, namely extreme malnutrition and muscle atrophy. Presented as one. Researchers studying the use of antibodies against GDF15 to combat cachexia. ”
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University of Barcelona
Quote: A new pathway for energy metabolism in peripheral tissues regulated by the cytokine GDF15 (2021, September 15) is https: //phys.org/news/2021-09-pathway-energy-metabolism-peripheral-tissues.html Obtained from September 15, 2021.
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A new pathway of energy metabolism in peripheral tissues regulated by the cytokine GDF15
Source link A new pathway of energy metabolism in peripheral tissues regulated by the cytokine GDF15