2545-P: Somatosensory Control of Adipose Tissue Metabolism and Inflammation

Introduction and Objective: Obesity promotes metabolic disease by impairing adipose tissue function and inducing chronic inflammation. While sympathetic regulation of adipose metabolism is well established, the contribution of sensory neurons remains poorly defined. To determine whether TRPV1+ sensory neurons regulate adipose thermogenesis and metabolic homeostasis, we used genetic and AAV-based approaches to trace and selectively delete Trpv1 in adipose-innervating sensory neurons. Methods: AAV-ROOT vectors (mScarlet and Cre) were injected into brown and white adipose tissue of Trpv1 flox mice to trace TRPV1+ sensory neurons or delete TRPV1 in adipose-innervating sensory neurons. Dorsal root ganglia (DRGs) were isolated for single-cell RNA sequencing to compare transcriptional profiles in lean, diet-induced obese, and GLP-1-treated mice. To validate findings, Trpv1 flox;Nav1.8-Cre mice were used, followed by parallel physiological and molecular analyses. Results: Early data suggest that targeted TRPV1 deletion results in a significant increase in brown adipose tissue thermogenic and mitochondrial gene expression. This manipulation did not alter tyrosine hydroxylase-positive sympathetic innervation or TH protein levels in brown adipose tissues, indicating that enhanced thermogenic gene expression occurs independently of changes in sympathetic input. Conclusion: These findings support a role for TRPV1+ sensory neurons in the regulation of brown adipose tissue thermogenesis. In this completed study we will establish a functional framework for how TRPV1+ sensory neurons influence adipose-CNS communication and drive metabolic outcomes in obesity. Disclosure I.G. Joseph: None. H.E. Cervantes: None. R. Tonello: None. T. Duarte Afonso Serdan: None. F. Shamsi: None.