The liver is a quiet yet essential guardian of the human body’s overall metabolic balance and, thus, responds sensitively to extreme environments. Microgravity exposure has been consistently associated with hepatic lipid metabolism dysregulation, characterized by increased intracellular lipid droplet accumulation in hepatocytes. Prolonged spaceflight further elevates the probability of developing metabolic dysfunction–associated steatotic liver disease (MASLD), a major health concern previously linked to chronic lipid overload and mitochondrial stress in hepatic tissue. Despite growing evidence of these effects, how hepatocytes sense gravity and convert mechanical cues into transcriptional and metabolic responses remains unclear.
To address this issue, a team led by Professor Mian Long from the Institute of Mechanics, Chinese Academy of Sciences, China, investigated the effects of space microgravity on hepatocytes cultured with or without shear flow aboard the China Space Station. Results show that space microgravity induces abnormal intracellular lipid droplet accumulation in hepatocytes under static culture conditions. In contrast, physiologically relevant shear flow effectively alleviates this effect during in vitro culture. Transcriptomic and proteomic analyses reveal that spaceflight promotes the synthesis of fatty acids and cholesterol through activation of sterol regulatory element-binding proteins (SREBPs). F-actin remodeling was confirmed to modulate SREBP activation under microgravity. Importantly, shear flow exhibits a protective effect by partially mitigating this metabolic dysregulation via preservation of F-actin structural integrity. These findings suggest that SREBPs may serve as gravity-sensitive regulators of lipid balance in hepatocytes, highlighting potential therapeutic targets for maintaining liver health in space travelers during long-duration missions.