mTOR信号通路介导短链脂肪酸调控PLIN3表达促进乳脂合成

Regulation of short-chain fatty acids on PLIN3 expression and promotion of milk fat synthesis mediated by mTOR signaling pathway

围脂滴蛋白3(Perilipin 3,PLIN3)是围脂滴蛋白家族成员之一,已被证实与脂滴初生相关,主要负责甘油三酯(Triglyceride,TAG)向脂滴的掺入。奶牛乳腺是乳脂合成旺盛器官,PLIN3在泌乳乳腺中表达,但其是否参与乳腺中乳脂合成尚不明确。采用基因过表达及Western blot等方法检测PLIN3对奶牛乳腺上皮细胞中TAG含量的影响,通过添加乳脂合成前体物以及抑制剂方法研究mTOR信号通路对PLIN3表达的调节。结果表明,PLIN3过表达极显著提高奶牛乳腺上皮细胞中TAG含量(P<0.01)。短链脂肪酸乙酸和β-羟基丁酸激活mTOR信号通路,提高细胞中PLIN3表达;采用雷帕霉素抑制mTOR信号通路激活则显著抑制短链脂肪酸对PLIN3表达的诱导作用(P<0.05)。该结果提示PLIN3表达与奶牛乳腺上皮细胞中乳脂合成相关,乙酸和β-羟基丁酸通过激活mTOR信号通路调节PLIN3表达,促进乳脂合成。

Perilipin 3(PLIN3)is a member of the perilipin family.PLIN3 has been demonstrated to be related to the initiation of lipid droplet(LD),which function is help triacylglycerol(TAG)incorporate into LD.Mammary gland can synthesize milk fat during lactation.PLIN3 is highly expressed in lactating mammary tissues of dairy cows.However,whether it participates in milk fat synthesis remains unknown.In this study,the effects of PLIN3 on TAG synthesis in cultured mammary epithelial cells of dairy cows were detected by gene overexpression and Western blot methods.Then,using milk fat synthesis precursors and inhibitor treatment,the regulation of mTOR signaling on PLIN3 expression was investigated.The results showed that PLIN3 overexpression extremely significantly increased intracellular TAG content(P<0.01).Acetate and BHBA could activate mTOR signaling pathway and improve PLIN3 expression level.Treatment cells with rapamycin inhibited acetate and BHBA-induced PLIN3 expression(P<0.05).These data indicated that PLIN3 was involved in milk fat synthesis in mammary gland of dairy cows.Acetate and BHBA increased PLIN3 expression via mTOR signaling activation,which in turn induced milk fat synthesis.