Acetate-Induced Milk Fat Synthesis Is Associated with Activation of the mTOR Signaling Pathway in Bovine Mammary Epithelial Cells.
Acetate-Induced Milk Fat Synthesis Is Associated with Activation of the mTOR Signaling Pathway in Bovine Mammary Epithelial Cells.
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DOI：
10.3390/ani12192616
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发表时间：
2022-09-29
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雷帕霉素（mTOR）通路的机制靶标在促进脂肪生成中起着至关重要的作用。乙酸诱导脂肪酸的从头脂肪生成以在牛乳腺上皮细胞（BMEC）中合成乳脂。我们假设醋酸盐可以通过激活BMEC中的mTOR信号通路来增强脂肪生成基因的表达和甘油三酯（TG）的产生。这些结果表明，用乙酸盐处理的BMEC中TG合成升高（p <0.01），并且用乙酸盐处理的BMEC中的脂肪酸谱受到影响。在BMEC中，与脂肪生成有关的基因的mRNA水平在乙酸盐中上调（p <0.05）。值得注意的是，乙酰辅酶A羧化酶α（ACC α）和脂肪酸合成酶（FAS）限速酶的表达在乙酸处理的BMEC中上调。此外，乙酸的加入增强了S6K1激酶的蛋白表达。综上所述，这些结果表明乙酸诱导的TG积累和脂肪生成基因的表达与mTOR信号通路的激活相关。乙酸是牛乳腺上皮细胞（BMEC）脂肪酸合成的前体物质，mTOR信号通路在乳脂合成中起重要作用。然而，醋酸盐通过mTOR信号通路对BMEC中脂肪生成基因的调节作用的机制仍然未知。我们假设醋酸盐可以通过激活BMEC中的mTOR信号通路来增强脂肪生成基因的表达和甘油三酯（TG）的产生。因此，本研究的目的是研究醋酸盐调节的脂质代谢的网络中的BMEC的mTOR信号通路。这些结果表明，用乙酸处理的BMEC中TG合成增加（p <0.01）。通过脂质的Bodipy染色，与对照组相比，醋酸盐处理组的脂滴增加。此外，用乙酸盐处理的BMEC中的脂肪酸谱受到影响，C14：0、C16：0和C18：0的比例升高。在乙酸处理的BMEC中，参与脂肪生成和转录因子的固醇反应元件结合蛋白1（SREBP 1）、硬脂酰辅酶A去饱和酶1（SCD 1）和脂肪酸合成酶（FAS）基因的mRNA水平上调（p <0.05）。值得注意的是，乙酰辅酶A羧化酶α（ACC α）和FAS限速酶参与脂肪生成的表达上调BMEC与乙酸处理。此外，乙酸的加入增强了与mTOR信号通路相关的S6K1的关键蛋白表达。总之，我们的数据表明，TG的积累和脂肪基因的表达诱导乙酸与mTOR信号通路的激活，这提供了新的见解的mTOR信号通路调节脂肪基因的表达的分子机制的理解。
The mechanistic target of the rapamycin (mTOR) pathway plays a vital role in promoting lipogenesis. Acetate induces de novo lipogenesis of fatty acids to synthesize milk fat in bovine mammary epithelial cells (BMECs). We hypothesized that acetate can enhance the expression of lipogenic genes and triglyceride (TG) production by activating the mTOR signaling pathway in BMECs. These results showed that TG synthesis was elevated (p < 0.01) in BMECs with acetate treatment, and the fatty acid profile in BMECs treated with acetate was affected. The mRNA levels of genes involved in the lipogenesis were upregulated (p < 0.05) in BMECs with acetate. Remarkably, expression of acetyl-CoA carboxylase α (ACCα) and fatty acid synthase (FAS) rate-limiting enzymes were upregulated in BMECs with acetate treatment. Moreover, the addition of acetate enhanced the protein expression of S6K1 kinase. In conclusion, these results suggest that the TG accumulation and expression of lipogenic genes induced by acetate are associated with the activation of the mTOR signaling pathway. Acetate is a precursor substance for fatty acid synthesis in bovine mammary epithelial cells (BMECs), and the mTOR signaling pathway plays an important role in milk fat synthesis. However, the mechanism of the regulatory effects of acetate on lipogenic genes via the mTOR signaling pathway in BMEC remains unknown. We hypothesized that acetate can enhance the expression of lipogenic genes and triglyceride (TG) production by activating the mTOR signaling pathway in BMECs. Therefore, the aim of this study was to investigate the network of acetate-regulated lipid metabolism by the mTOR signaling pathway in BMECs. These results showed that TG synthesis was elevated (p < 0.01) in BMECs with acetate treatment. The lipid droplets were increased in the acetate-treated groups compared with those in the control group through the Bodipy staining of the lipids. In addition, the fatty acid profile in BMECs treated with acetate was affected, with an elevation in the proportions of C14:0, C16:0, and C18:0. The mRNA levels of the sterol-response-element-binding protein 1 (SREBP1), stearoyl-CoA desaturase 1 (SCD1), and fatty acid synthase (FAS) genes involved in the lipogenesis and transcriptional factors were upregulated (p < 0.05) in BMECs with acetate treatment. Remarkably, the expression of acetyl-CoA carboxylase α (ACCα) and FAS rate-limiting enzymes involved in lipogenesis was upregulated in BMECs with acetate treatment. Moreover, the addition of acetate enhanced the key protein expression of S6K1, which is related to the mTOR signaling pathway. Taken together, our data suggest that TG accumulation and expression of lipogenic genes induced by acetate are associated with the activation of the mTOR signaling pathway, which provides new insights into the understanding of the molecular mechanism in the expression of mTOR-signaling-pathway-regulated lipogenic genes.
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