Core Viewpoint - The research reveals how fetal liver maintains active anabolic metabolism in a low glucose environment through specific post-translational modification of TRPV4 protein, which prevents the inhibition of mTORC1, thus safeguarding fetal development [3][17]. Metabolic Regulation - Two key metabolic regulators in mammalian cells are mTORC1 and AMPK. mTORC1 promotes anabolic processes when nutrients are abundant, while AMPK is activated during energy deficiency to promote catabolism [6][7]. Fetal Liver's Unique Mechanism - The resistance to low glucose-induced mTORC1 inhibition occurs specifically in fetal liver tissue, unlike other fetal tissues such as heart, lung, and muscle, where mTORC1 is significantly inhibited under similar conditions [9]. Mechanism Exploration - The study identifies TRPV4 protein as crucial for this phenomenon. In fetal liver, TRPV4 undergoes acetylation at the K608 site, making it insensitive to inhibition by unbound aldolase, thus blocking the low glucose signal to mTORC1 [11][12]. Regulatory Network - The high acetylation level of TRPV4 in fetal liver is maintained by a precise regulatory network involving acetyltransferase P300 and deacetylases SIRT2 and SIRT7. This indicates that TRPV4's acetylation is not driven by substrate concentration but by enzyme activity [14]. Clinical Significance - Understanding how fetuses maintain growth in low-nutrition environments could provide new strategies for preventing and treating intrauterine growth restriction, which affects approximately 5%-10% of pregnancies [17]. Additionally, this discovery may offer new insights into metabolic diseases and cancers related to abnormal mTORC1 signaling [18].