Screening for blood-borne biomarkers of adiponectin action using the receptor agonist ALY688
The employment of adiponectin-based therapeutic strategies emerges as a compelling approach in the management of diverse metabolic pathologies and the attenuation of inflammatory processes. This has precipitated the development of adiponectin receptor agonists. However, the effective surveillance of pharmacodynamic actions within the context of clinical applications remains challenging. Therefore, in this study we attempted to identify and translate peripheral biomarkers to monitor adiponectin actions in blood samples, by using a small, 10 amino acid peptide, adiponectin receptor agonist, ALY688. RNA-sequencing analysis of whole blood validated the anti-inflammatory effect of ALY688 in a sublethal LPS mouse model treated with or without ALY688. Furthermore, RNAseq analysis identified a cluster of genes, including Tgfb2, Rorc, and Il17rb, that was significantly increased in the group administered ALY688 in comparison to vehicle treated group. This cluster of differentially expressed genes was validated by real-time quantitative PCR and further verified in human peripheral blood mononuclear cells treated with ALY688 ex vivo. Collectively, these data established anti-inflammatory effects of ALY688 and identified a gene cluster signature that can be assessed in blood samples to rapidly and easily biomarker pharmacodynamic action of adiponectin or its mimetics. Overall design: Plasma of mice injected with or without ALY688 was performed RNA sequencing to indentify biomarkers for monitoring ALY688 action. Besides, to validate the anti-inflammatory effects of ALY688, we conducted RNA-sequencing analysis of whole blood in a sublethal LPS mouse model, comparing outcomes between mice treated with ALY688 and those left untreated.