This study was conducted to explore the molecular mechanisms of berberine (Ber) via peroxisome proliferator-activated receptor gamma (PPARG) in promoting in vitro maturation (IVM) and lipid metabolism of porcine oocytes. Our results showed that expression changes in PPARG influenced IVM and the lipid droplet content of porcine oocytes. Moreover, c-Jun-N-terminal kinase (JNK) inhibitor modified the effect of PPARG agonist on IVM and lipid droplet content of porcine oocytes, and Ber significantly reduced lipid droplet content. Activation of PPARG upregulated the transcription level of microRNA-192 (miR-192), significantly promoted the expression of fatty acid binding protein 3 (FABP3) and steroid regulatory element binding transcription factor 1 (SREBF1) and PPARG, inhibited phosphorylation of PPARG, and enhanced JNK phosphorylation. Ber and overexpression of miR-192 upregulated the transcription level of miR-192 in porcine oocytes; significantly decreased the expression of FABP3, SREBF1, and PPARG; increased PPARG phosphorylation; and inhibited JNK phosphorylation. Otherwise, JNK inhibitor reduced the effects of PPARG agonist. In conclusion, Ber may activate the expression of miR-192, downregulate the expression level of PPARG and lipid synthesis-related genes, increase PPARG phosphorylation, and reduce JNK phosphorylation to enhance lipid metabolism, which is beneficial to improve porcine oocyte quality of IVM.

中文翻译：

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猪卵母细胞体外成熟过程中小檗碱通过过氧化物酶体增殖物激活受体γ促进脂质代谢的机制

本研究旨在探讨小檗碱（Ber）通过过氧化物酶体增殖物激活受体γ（PPARG）促进猪卵母细胞体外成熟（IVM）和脂质代谢的分子机制。我们的结果表明，PPARG 的表达变化影响 IVM 和猪卵母细胞的脂滴含量。此外，c-Jun-N-末端激酶 (JNK) 抑制剂改变了 PPARG 激动剂对猪卵母细胞 IVM 和脂滴含量的影响，Ber 显着降低了脂滴含量。PPARG 的激活上调了 microRNA-192 (miR-192) 的转录水平，显着促进了脂肪酸结合蛋白 3 (FABP3) 和类固醇调节元件结合转录因子 1 (SREBF1) 和 PPARG 的表达，抑制了 PPARG 的磷酸化，并且增强的 JNK 磷酸化。Ber和miR-192的过表达上调了猪卵母细胞中miR-192的转录水平；显着降低 FABP3、SREBF1 和 PPARG 的表达；增加 PPARG 磷酸化；并抑制 JNK 磷酸化。否则，JNK 抑制剂会降低 PPARG 激动剂的作用。综上所述，Ber可能通过激活miR-192的表达，下调PPARG及脂质合成相关基因的表达水平，增加PPARG磷酸化，降低JNK磷酸化从而促进脂质代谢，有利于提高IVM猪卵母细胞质量。JNK 抑制剂降低了 PPARG 激动剂的作用。综上所述，Ber可能通过激活miR-192的表达，下调PPARG及脂质合成相关基因的表达水平，增加PPARG磷酸化，降低JNK磷酸化从而促进脂质代谢，有利于提高IVM猪卵母细胞质量。JNK 抑制剂降低了 PPARG 激动剂的作用。综上所述，Ber可能通过激活miR-192的表达，下调PPARG及脂质合成相关基因的表达水平，增加PPARG磷酸化，降低JNK磷酸化从而促进脂质代谢，有利于提高IVM猪卵母细胞质量。