Strontium regulating lipid metabolism of bovine hepatocytes via SIRT1/SREBPs pathway

Abstract

Periparturient dairy cows are susceptible to negative energy balance (NEB), which triggers excessive adipose mobilization, leading to elevated plasma non-esterified fatty acids (NEFA) and hepatic lipid accumulation. While strontium (Sr) has shown metabolic regulatory potential, its role in hepatic lipid homeostasis remains unclear. Using an NEFA-induced lipid accumulation model in bovine hepatocytes, we demonstrated that Sr (5–20 μM) significantly reduced intracellular triglyceride (TG) and total cholesterol (TC) levels. Further mechanistic studies revealed that Sr enhances SIRT1 expression and suppresses the expression and nuclear translocation of SREBP-1C/SREBP2, thereby downregulating downstream lipogenic enzymes including ACC, FASN, SCD1, and HMGCR. Molecular docking indicated that Sr²⁺ binds with high affinity to Asp-481/483 of SIRT1, while SIRT1 inhibition with EX-527 abolished Sr-mediated lipid-lowering effects. Additionally, Sr promoted PPARα nuclear translocation to enhance β-oxidation and upregulated LDLR expression to facilitate lipid efflux. This study elucidated the multi-target molecular mechanism of Sr alleviating lipid metabolism disorders in bovine hepatocytes through the SIRT1/SREBPs pathway, providing a theoretical foundation for the application of Sr in preventing metabolic diseases in dairy cows.