Curcumin Attenuates Lipopolysaccharide-Induced Hepatic Lipid Metabolism Disorder by Modification of m6A RNA Methylation in Piglets
Curcumin Attenuates Lipopolysaccharide-Induced Hepatic Lipid Metabolism Disorder by Modification of m6A RNA Methylation in Piglets
复制标题
姜黄素通过修饰仔猪 m(6)A RNA 甲基化来减轻脂多糖诱导的肝脏脂质代谢紊乱
DOI：
10.1002/lipd.12023
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发表时间：
2018-01-01
期刊：
影响因子：
1.9
通讯作者：
Zhong, Xiang
中科院分区：
文献类型：
--
作者：
Lu, Na;Li, Xingmei;Zhong, Xiang
N-6-甲基腺苷 (m(6)A) 调节基因表达并影响细胞代谢。在本研究中，我们检查了姜黄素对脂质代谢的调节是否与 m(6)A RNA 甲基化相关。我们研究了日粮中添加姜黄素对脂多糖 (LPS) 诱导的肝损伤和脂质代谢紊乱以及断奶仔猪 m(6)A RNA 甲基化的影响。总共 24 头杜洛克 x 大白 x 长白仔猪被随机分配到对照组、LPS 和 CurL（LPS 攻击和 200mg/kg 日粮姜黄素）组（n = 8/组）。结果表明，姜黄素降低了断奶仔猪血浆和肝脏中LPS注射引起的相对肝脏重量的增加以及天冬氨酸转氨酶和乳酸脱氢酶的浓度（p < 0.05）。与 LPS 注射相比，姜黄素降低了总胆固醇和三酰甘油的含量 (p < 0.05)。此外，姜黄素降低了 Bcl-2 和 Bax mRNA 的表达，而增加了肝脏中 p53 mRNA 的水平 (p < 0.05)。姜黄素抑制LPS诱导的肝脏中SREBP-1c和SCD-1 mRNA水平的增强。值得注意的是，日粮姜黄素影响 METTL3、METTL14、ALKBH5、FTO 和 YTHDF2 mRNA 的表达，并增加仔猪肝脏中 m(6)A 的丰度。总之，姜黄素对 LPS 诱导的肝损伤和肝脂质代谢紊乱的保护作用可能是由于 m(6)A RNA 甲基化的增加。我们的研究提供了姜黄素在炎症和代谢疾病期间预防肝损伤作用的机制见解。
N-6-methyladenosine (m(6)A) regulates gene expression and affects cellular metabolism. In this study, we checked whether the regulation of lipid metabolism by curcumin is associated with m(6)A RNA methylation. We investigated the effects of dietary curcumin supplementation on lipopolysaccharide (LPS)-induced liver injury and lipid metabolism disorder, and on m(6)A RNA methylation in weaned piglets. A total of 24 Duroc x Large White x Landrace piglets were randomly assigned to control, LPS, and CurL (LPS challenge and 200mg/kg dietary curcumin) groups (n = 8/group). The results showed that curcumin reduced the increase in relative liver weight as well as the concentrations of aspartate aminotransferase and lactate dehydrogenase induced by LPS injection in the plasma and liver of weaning piglets (p < 0.05). The amounts of total cholesterol and triacylglycerols were decreased by curcumin compared to that by the LPS injection (p < 0.05). Additionally, curcumin reduced the expression of Bcl-2 and Bax mRNA, whereas it increased the p53 mRNA level in the liver (p < 0.05). Curcumin inhibited the enhancement of SREBP-1c and SCD-1 mRNA levels induced by LPS in the liver. Notably, dietary curcumin affected the expression of METTL3, METTL14, ALKBH5, FTO, and YTHDF2 mRNA, and increased the abundance of m(6)A in the liver of piglets. In conclusion, the protective effect of curcumin in LPS-induced liver injury and hepatic lipid metabolism disruption might be due to the increase in m(6)A RNA methylation. Our study provides mechanistic insights into the effect of curcumin in protecting against hepatic injury during inflammation and metabolic diseases.