Unraveling Hepatic Osmoregulation in Teleost: Metabolic Reprogramming and Signal Transduction in Salinity Adaptation

ABSTRACT Salinity stress is a major threat to aquaculture, posing formidable challenges to the acclimation and survival of farmed fish, particularly teleosts. Although the liver of teleosts is not considered a primary osmoregulatory organ and its contribution to osmoregulation is frequently overlooked, it in fact plays an indispensable role in fish adaptation to salinity changes through its involvement in energy supply and allocation, ion transport, signal transduction, immune response, and cellular structural regulation. Central to the energy‐related function, the liver regulates glucose and lipid turnover to fuel osmotic stress responses. Beyond energy provision, hepatocytes also participate in water, ion, and organic osmolyte (e.g., urea, taurine) trafficking via regulated expression of aquaporins (AQPs) and transmembrane transporters. The liver further contributes to osmotic signal transduction through the expression of cell adhesion molecules, ion channel receptors, and ion channel regulatory proteins, enabling the propagation and amplification of salinity stress signals. Moreover, it participates in regulating the expression of inflammatory factors and antioxidant enzymes, metabolic reallocation, and protein homeostasis, helping teleosts maintain immune homeostasis under osmotic stress, optimize energy allocation between immune and osmotic regulation, and reduce cellular damage, thereby adapting to salinity changes. Building upon a decade of research advances in hepatic osmoregulatory mechanisms, this review systematically synthesizes the liver's multifaceted roles in teleost salinity adaptation, including glucolipid metabolic reprogramming, osmosensory signaling, cytoskeleal remodeling, and hormonal coordination. We further compare the water‐electrolyte balance strategies employed by different ecological types of teleosts, while offering forward‐looking insights into future research directions for sustainable aquaculture: (1) using multi‐omics and gene editing to identify and integrate key genes regulating hepatic metabolism and osmotic adaptation into breeding programs; (2) elucidating interactions between hepatic energy metabolism and organic osmolytes (e.g., taurine, betaine) for developing targeted nutritional strategies; (3) identifying the research gaps in hepatic urea‐based osmoregulation of teleosts.