Glial Plasticity and Metabolic Stability After Knockdown of Astrocytic Cx43 in the Dorsal Vagal Complex

Obesity causes millions of deaths each year due to metabolic complications, making it a major public health challenge. It results from a chronic imbalance between caloric intake and energy expenditure. Among central structures regulating energy balance, the dorsal vagal complex (DVC) integrates metabolic signals from energy stores and the gastrointestinal tract and coordinates autonomic responses. While historically overshadowed by a focus on neurons, the role of glial cells in regulating energy balance is now well established. Connexin 43 (Cx43) is a well-known protein expressed by astrocytes, playing a key role in glial and neuroglial communication. To investigate the role of astrocytic Cx43 within the DVC, where its expression is remarkably high, we specifically reduced it using an RNA interference approach. Although reduced Cx43 expression led to modified astrocyte and microglia morphology and phenotype, our analyses did not reveal significant changes in the animal's metabolic phenotype under standard feeding conditions as well as under a high-fat, high-sugar diet. These results suggest that denser astrocytic tiling and hyper-ramified microglia may constitute a buffering system that preserves metabolic and autonomic outputs when a single connexin pathway fails.