Sphingosine kinase 2 deficiency impairs VLDL secretion by inhibiting mTORC2 phosphorylation and activating chaperone-mediated autophagy.

ABSTRACT: Hepatic very low-density lipoprotein (VLDL) is essential for maintaining lipid metabolism in the liver. Sphingosine kinases (SphKs) are essential rate-limiting enzymes that catalyze sphingosine phosphorylation to Sphingosine-1-phosphate (S1P). SphKs exist as two isoforms, SphK1 and SphK2, both highly expressed in the liver. SphK1 plays a critical role in regulating hepatic inflammation and drug metabolism. This study aimed to determine whether SphK2 regulates hepatic lipid metabolism, particularly VLDL secretion. Immunohistochemical staining revealed decreased SphK2 protein levels within regions proximal to hepatic lipid accumulation in individuals diagnosed with metabolic dysfunction-associated steatotic liver disease (MASLD). Sphk2^-/- mice exhibited spontaneous hepatocyte lipi

SUBMITTER: Zhang S 

PROVIDER: S-EPMC12500862 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature