Abstract

Liver function is critical for maintenance of body homeostasis since it regulates several metabolic processes, including glucose and fatty acids metabolism. Metabolic and nutritional altered states such as obesity, insulin resistance and diabetes negatively impact the liver leading to a condition termed Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). Connexins (Cxs) and pannexins (Panxs) are plasma membrane channels, central for correct liver function, including the coordination of metabolic functions. These channels allow direct communication between the cytoplasm of adjacent cells or via paracrine signaling. Overnutrition conditions that lead to MASLD impact Cxs and Panxs channel functions in hepatocytes. Changes in Cxs and Panxs expression during hepatic metabolic disturbances further contribute to the pathogenesis of MASLD. This situation appears to be a pathological condition, which involves alterations mainly in the expression of connexin 43 (Cx43), connexin 32 (Cx32) and pannexin 1 (Panx1) in the transmission of damage signals. In the liver, Panx1 activity is traditionally associated with inflammation and apoptosis. Nevertheless, recent findings challenge this view. Therefore, these channels and their associated pathways arise as potential therapeutic targets in liver metabolic conditions such as MASLD. In this narrative review we analyzed the role of Cxs and Panxs channels in the development of this pathology as well as possible targets for treatment.