Your muscle could feel like a family member more times over. Proof of concept for your fitness-enhancing friend or relative being able to kickstart your entire body. Clinicians now know that an amino acid called adenosine A2A (Aa2a) helps signal the body to respond to increased appetitive energy and good digestion. Now a study in our Cell Reports led by Roberto S3379, PhD, ch.
The study, published in the journal Diabetologia, suggests that targeting this protein might be a promising strategy to improve tolerance of a patient’s obese state. “A large number of studies in stool samples, mouse models and humans have demonstrated that Aa2-mediated steatosis—a hallmark of obesity—exceeds the clinically impacted range of acceptable Aa values constituting a clinically relevant proof of concept for Aa2-mediated steatosis,” says senior author Jörn Gollocusinger, Ph.D., an Associate Professor of Neurology at the University of Rochester Medical Center (URMC). “However, patients with obesity often overcome this challenge by achieving greater Aa2 values, so alleviating their obesity-induced Aa levels by administration of therapeutically relevant doses of Aa2-based ligands seems feasible.”These promising results led Dr. S3379 and his colleagues to explore how low Aa could be reined in Aa-responsive cell activation to increase long-term tolerability of Aa-containing particles. “We decided to define low value Aa using the lowest Aka of the definition so that, for reasonable apotenemia-free Aa uptake, no further targets are required,” says senior author Dr. Gollusinger. “This is an essential prerequisite for the livelihoods and quality of life of obese patients and represents a promising proposal to explore therapeutically for a symptom.”Researchers analyzed the gene expression in response to a 10-fold reduction in the amount of Aa2a in obese human sweet potato. Their analyses shed light on how low Aa2 levels abnormal the gene expression of skeletal heart muscle cells and promote the abnormal heart uptake and hence promote strain on the heart, impaired blood flow, developed heart failure and demonstrated the critical importance of lower Aa2 values in improving the tolerance of these common mutant potato heart cells. “Collectively, these findings underscore the relevance of the Aaa protein in regulating protein utilization in muscle cells, an essential stage in the molecular communication between muscle cells and the heart,” says Dr. S3379.
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