Grant: CIHR-ICRH Travel Awards - General pool

Introduction: Obesity is associated with dysfunctional white adipose tissue (WAT), characterized by enlarged adipocytes, poor vascularization, innervation, and high macrophage infiltration. The factors controlling WAT growth are not well understood. EMPRD, a secreted protein expressed in the brain and pre-adipocytes, has been recently identified. In vitro experiments have shown that depleting EMPRD impairs adipogenesis, while its overexpression induces it. However, the effects of EMPRD overexpression in vivo remain unclear. Our objective is to determine the role of EMPRD overexpression in vivo. Methods: Mice were injected with adenoviruses to overexpress EMPRD. These mice were then fed a chow or high-fat diet for 3 weeks and body weight measurement was followed. Glucose and insulin tolerance tests were performed. At the end of the study, metabolic genes and blood metabolites were analyzed. Results: EMPRD overexpressing mice showed significant reductions in body and fat pad weight. Moreover, glucose and lipid metabolic profiles were improved as glucose and triglyceride levels were significantly reduced in response to EMPRD overexpression. This was associated with an important improvement in glucose and insulin tolerance. Interestingly, when EMPRD faded away, the observed effects were lost, indicating their reversibility and direct dependence on EMPRD. Histological analysis of liver tissue from mice overexpressing EMPRD showed abnormal organization, and RNA sequencing revealed the downregulation of liver-specific genes (38.4%) and upregulation of brain-specific genes (16.5%). Given that Emprd is typically expressed in the brain and that liver innervation is known to play a key role in regulating blood glucose levels, our findings suggest that EMPRD may influence liver innervation and thus contribute to the regulation of glycemia. Conclusion: Our findings provide new insights into the potential role of EMPRD in metabolic regulation and may have implications for the development of therapies for metabolic disorders.