Project description:Animals rely on linear growth to attain their full adult size. The regulators of this multifactorial process, including environmental and endocrine cues, are still incompletely understood. Notably, GLP-1, glucagon-like peptide 1 (GLP-1) has emerged as a potential player in this process. Here, we employ semaglutide, a pharmaceutical GLP-1R agonist as a tool to mechanistically dissect the interplay between GLP-1 receptor activation, energy metabolism, and linear growth during the juvenile period, independent of its clinical applications. Using a juvenile mouse model, we show that chronic semaglutide treatment lowers blood glucose without affecting food intake or weight gain in juveniles with a normal growth pattern. However, in growth-stunted juveniles, semaglutide treatment exacerbates linear growth impairment through at least 2 concomitant mechanisms: a moderate reduction in food intake, and a decreased catabolic activity incompatible with tissue growth. These data suggest a complex interplay between GLP-1 signaling, energy metabolism, and growth during juvenile development. Overall, these findings highlight the value of semaglutide as a mechanistic tool for understanding how GLP-1 receptor activation modulates growth and metabolism in juveniles, emphasizing the importance of developmental context for interpreting its effects.
Project description:It has been widely recognized that Acute kidney injury (AKI)represents a multifactorial, heterogeneous syndrome, or a spectrum of diseases. AKI is associated with prolonged hospitalization and high mortality, and it predisposes individuals to chronic kidney disease. To date, no effective AKI treatments have been established. This study used single-cell RNA sequencing (scRNA-seq) to explore novel molecular mechanisms and gene targets for AKI. We identifies a distinct cell-specific gene expression profile, pathogenic signaling pathways and potential cell-cell communications in the pathogenesis of AKI. These findings will provide a promising novel landscape for mechanisms and treatment of AKI.
Project description:To understand the consequences of chronic exposure to fluoxetine during juvenile life on global transcriptional changes withing the rat medial prefrontal cortex in adulthood. To understand the consequences of chronic exposure to fluoxetine during juvenile life on global transcriptional changes withing the rat medial prefrontal cortex in adulthood.