Effects of SIRT7 Inhibition on Milk Fat Synthesis and Fatty Acid Composition in Dairy Goat Mammary Epithelial Cells

Simple SummarySirt7, a member of the NAD+-dependent class III histone deacetylase family (Sirtuins), is involved in the regulation of multiple metabolic processes, including glucose homeostasis and energy balance, and plays a key regulatory role in lipid metabolism. The present study demonstrates that inhibition of Sirt7 increases the expression of SREBP1 and downstream lipogenic genes, thereby enhancing lipid droplet accumulation and triglyceride levels, while also improving the fatty acid profile. These findings help to elucidate the molecular mechanisms by which Sirt7 regulates lipid metabolism and provide a deeper understanding of the regulatory mechanisms underlying milk fat synthesis in mammary epithelial cells of dairy goats.Milk fat, a key nutritional component of milk, not only supplies energy and immune protection for offspring but also serves as a critical quality indicator for goat milk. Sirt7, one of the least studied members of the Sirtuins family, has been shown to play a regulatory role in lipid metabolism. This study investigated the regulatory role of Sirt7 in milk fat synthesis and fatty acid composition in dairy goat mammary epithelial cells (GMECs) using a Sirt7 inhibitor (ID: 97491). GMECs were treated with a Sirt7 inhibitor (ID: 97491), and cell viability was assessed via the CCK-8 assay, which confirmed that 15 μmol/L inhibitor had no cytotoxic effects. Functional analyses using RT-qPCR, Western blot, and GC-MS revealed that Sirt7 inhibition upregulated the expression ofSREBP1,CD36,ACC,SCD1, andELOVL6while downregulatingFOXO1andFABP1. At the protein level, the inhibitor reduced Sirt7, FOXO1. Additionally, Sirt7 inhibition increased intracellular lipid droplet and triglyceride content. GC-MS analysis showed that Sirt7 inhibition decreased C11:0; increased C16:0, C15:0, C20:0, C24:0, C16:1, and C18:1n9c; and decreased C20:5n3 (EPA). Collectively, these findings suggest that pharmacological inhibition of Sirt7 is associated with upregulation of SREBP1, disruption of lipid homeostasis, triglyceride accumulation, and altered fatty acid composition in GMECs. These results provide preliminary evidence for a potential regulatory role of Sirt7 in milk fat synthesis and lay a foundation for future mechanistic studies.