Liu Long, Wang Qian, Wang Qianqian, Zhao Xing, Zhao Pan, Geng Tuoyu, Gong Daoqing
College of Animal Science and Technology, Yangzhou University, Yangzhou, 225009, China.
BMC Vet Res. 2018 Nov 6;14(1):325. doi: 10.1186/s12917-018-1653-3.
A short period of overfeeding can lead to severe hepatic steatosis in the goose, which is physiological, suggesting that geese, as a descendent of a migrating ancestor, may have evolutionally developed a unique mechanism that operates in contrast to the mechanism underlying pathological fatty liver in humans or other mammals. In this study, we report that suppression of miR29c and upregulation of its target genes in goose fatty liver vs. normal liver could be part of a unique mechanism that contributes to the regulation of energy homeostasis and cell growth.
Our data showed that miR29c expression was comprehensively inhibited in energy homeostasis-related tissues (the liver, fat and muscle) of overfed vs. normally fed geese, which is different from miR29c induction that occurs in tissues of the diabetic rat. To address the function of miR29c, three predicted target genes (i.e., Insig1, Sgk1 and Col3a1) that participate in energy homeostasis or cell growth were validated by a dual-fluorescence reporter system and other in vitro assays. Importantly, expression of Insig1, Sgk1 and Col3a1 was upregulated in goose fatty liver. In line with these observations, treatment of goose hepatocytes with high glucose or palmitate suppressed the expression of miR29c but induced the expression of the target genes, suggesting that hyperglycemia and hyperlipidemia, at least partially, contribute to the suppression of miR29c and induction of the target genes in goose fatty liver. In addition, pharmacological assays indicated that RFX1 was a transcription factor involved in the expression of miR29c.
This study suggests that miR29c may play a role in the regulation of energy homeostasis and tissue growth via its target genes, contributing to the tolerance of the goose to severe hepatic steatosis.
短期过度喂养可导致鹅出现严重的肝脂肪变性，这是生理性的，这表明作为迁徙祖先后代的鹅，可能在进化过程中形成了一种独特的机制，该机制与人类或其他哺乳动物病理性脂肪肝的潜在机制相反。在本研究中，我们报告，与正常肝脏相比，鹅脂肪肝中miR29c的抑制及其靶基因的上调可能是有助于调节能量稳态和细胞生长的独特机制的一部分。
我们的数据表明，与正常喂养的鹅相比，过度喂养的鹅的能量稳态相关组织（肝脏、脂肪和肌肉）中miR29c的表达受到全面抑制，这与糖尿病大鼠组织中发生的miR29c诱导不同。为了研究miR29c的功能，通过双荧光报告系统和其他体外试验验证了三个参与能量稳态或细胞生长的预测靶基因（即Insig1、Sgk1和Col3a1）。重要的是，Insig1、Sgk1和Col3a1在鹅脂肪肝中的表达上调。与这些观察结果一致，用高糖或棕榈酸处理鹅肝细胞可抑制miR29c的表达，但诱导靶基因的表达，这表明高血糖和高血脂至少部分导致了鹅脂肪肝中miR29c的抑制和靶基因的诱导。此外，药理学试验表明RFX1是参与miR29c表达的转录因子。
本研究表明，miR29c可能通过其靶基因在能量稳态和组织生长的调节中发挥作用，有助于鹅对严重肝脂肪变性的耐受性。
