Short-chain fatty acids are important nutrients that regulate milk fat synthesis. They regulate milk synthesis via the sterol regulatory element binding protein 1 (SREBP1) pathway; however, the details are still unknown. Here, the regulation and mechanism of sodium acetate (SA) in milk fat synthesis in bovine mammary epithelial cells (BMECs) were assessed. BMECs were treated with SA supplementation (SA+) or without SA supplementation (SA-), and milk fat synthesis and activation of the SREBP1 pathway were increased (P = 0.0045; P = 0.0042) by SA+ and decreased (P = 0.0068; P = 0.0031) by SA-, respectively. Overexpression or inhibition of SREBP1 demonstrated that SA promoted milk fat synthesis (P = 0.0045) via the SREBP1 pathway. Overexpression or inhibition of TATA element modulatory factor 1 (TMF1) demonstrated that TMF1 suppressed activation of the SREBP1 pathway (P = 0.0001) and milk fat synthesis (P = 0.0022) activated by SA+. Overexpression or inhibition of TMF1 and SREBP1 showed that TMF1 suppressed milk fat synthesis (P = 0.0073) through the SREBP1 pathway. Coimmunoprecipitation analysis revealed that TMF1 interacted with SREBP1 in the cytoplasm and suppressed the nuclear localization of SREBP1 (P = 0.0066). The absence or presence of SA demonstrated that SA inhibited the expression of TMF1 (P = 0.0002) and the interaction between TMF1 and SREBP1 (P = 0.0001). Collectively, our research suggested that TMF1 was a new negative regulator of milk fat synthesis. In BMECs, SA promoted the SREBP1 pathway and milk fat synthesis by suppressing TMF1. This study enhances the current understanding of the regulation of milk fat synthesis and provides new scientific data for the regulation of milk fat synthesis.

短链脂肪酸是调节乳脂合成的重要营养物质。它们通过甾醇调节元件结合蛋白 1 (SREBP1) 途径调节乳汁合成；但是，细节仍然未知。在此，评估了乙酸钠 (SA) 在牛乳腺上皮细胞 (BMEC) 乳脂合成中的调节和机制。 BMECs 用 SA 补充剂 (SA+) 或不补充 SA (SA-) 处理，乳脂合成和 SREBP1 通路的激活因 SA+而增加 ( P = 0.0045  ; P = 0.0042) 而减少 ( P  = 0.0068; P  = 0.0031) 分别由 SA-。SREBP1 的过表达或抑制表明 SA 促进乳脂合成（P = 0.0045) 通过 SREBP1 通路。TATA 元件调节因子 1 (TMF1) 的过表达或抑制表明 TMF1 抑制了 SREBP1 通路的激活 ( P = 0.0001) 和 由 SA+ 激活的 乳脂合成 ( P = 0.0022)。 TMF1 和 SREBP1 的过表达或抑制表明 TMF1通过 SREBP1 途径抑制乳脂合成 ( P = 0.0073)。共免疫沉淀分析显示 TMF1 与细胞质中的 SREBP1 相互作用并抑制 SREBP1 的核定位 ( P  = 0.0066)。SA 的存在或不存在表明 SA 抑制 TMF1 的表达 ( P  = 0.0002) 以及 TMF1 和 SREBP1 之间的相互作用 ( P = 0.0001）。总的来说，我们的研究表明 TMF1 是一种新的乳脂合成负调节剂。在 BMEC 中，SA 通过抑制 TMF1 促进 SREBP1 通路和乳脂合成。该研究增进了目前对乳脂合成调控的认识，为乳脂合成的调控提供了新的科学数据。