Trodusquemine Influences the Metabolic Phenotype Through Pi3k/Akt/Mtor Pathway in Juvenile Male and Female Mice More Potently than Metformin

Postnatal development is a critical period during an organisms life that dictates not only growth and sexual maturity, but also determines longevity. Particularly, recent studies have demonstrated the remarkable potential of early-life intervention strategies at influencing the course of postnatal development, thereby offering exciting possibilities for enhancing longevity and improving overall health. Metformin (MF), an FDA approved medication for type II diabetes mellitus, has recently gained attention for its presumed anti-aging properties, acting as a calorie restriction mimetic, and delaying precocious puberty. Trodusquemine (MSI-1436), is a novel drug that has been shown to prevent obesity and metabolic disorders by inhibiting the enzyme protein tyrosine phosphatase 1b (PTP1B), reducing hepatic lipogenesis and counteracting insulin and leptin resistance. In this study, we aimed to further explore the effects of these compounds in young mice to uncover novel treatments to deter aging and age-related diseases. We examined the influence of MF and MSI-1436 on mRNA signatures that are central to liver metabolic processes while simultaneously profiling small, noncoding miRNAs which act as biomolecular switches due to their robust ability to control gene expression.