2045-LB: Target-Derived Factors Decrease Sympathetic Innervation of Brown Adipose Tissue in a Critical Period of Development

A wide range of developmental exposures can influence the establishment of sympathetic nervous system (SNS) tone onto metabolically relevant organs, but little is known about the underlying mechanism. Rearing mice at an ambient temperature of 30°C vs. 22°C from birth to 8 weeks of life programs lasting effects on SNS tone onto brown adipose tissue (BAT) and the capacity to respond to chronic cold challenges. We used this system to identify a critical period of development and potential molecular mediators of these effects. Utilizing cholera toxin B retrograde tracing we visualized sympathetic neurons in the stellate ganglion innervating BAT (SG^BAT). By comparing the number of SG^BAT neurons in mice reared at 30°C vs. 22°C across the first 8 weeks of life, we defined a time window when rearing at 30°C is associated with a marked decrease in innervation. Analyses of transcriptional profiles from bulk RNA-sequencing of BAT during this critical period revealed several signaling molecules that are differentially expressed at 30°C vs. 22°C. Complementary gain- and loss-of-function studies are underway to test the contribution of these candidate factors to the establishment of BAT SNS tone during development. Mechanisms identified here will provide a framework for analogous studies in other organs that are also implicated in developmental programming of health and disease.