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姜黄素通过改变仔猪的m⁶A RNA甲基化减轻脂多糖诱导的肝脏脂质代谢紊乱。

Curcumin Attenuates Lipopolysaccharide-Induced Hepatic Lipid Metabolism Disorder by Modification of m A RNA Methylation in Piglets.

作者信息

Lu Na, Li Xingmei, Yu Jiayao, Li Yi, Wang Chao, Zhang Lili, Wang Tian, Zhong Xiang

机构信息

College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, People's Republic of China.

Department of Animal Feed Science, Nanjing Hongshan Forest Zoo, Nanjing, People's Republic of China.

出版信息

Lipids. 2018 Jan;53(1):53-63. doi: 10.1002/lipd.12023.

Abstract

N -methyladenosine (m 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 A RNA methylation. We investigated the effects of dietary curcumin supplementation on lipopolysaccharide (LPS)-induced liver injury and lipid metabolism disorder, and on m A RNA methylation in weaned piglets. A total of 24 Duroc × Large White × Landrace piglets were randomly assigned to control, LPS, and CurL (LPS challenge and 200 mg/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 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 A RNA methylation. Our study provides mechanistic insights into the effect of curcumin in protecting against hepatic injury during inflammation and metabolic diseases.

摘要

N-甲基腺苷(m⁶A)调节基因表达并影响细胞代谢。在本研究中,我们检测了姜黄素对脂质代谢的调节是否与m⁶A RNA甲基化有关。我们研究了日粮添加姜黄素对脂多糖(LPS)诱导的断奶仔猪肝损伤、脂质代谢紊乱以及m⁶A RNA甲基化的影响。将24头杜洛克×大白×长白断奶仔猪随机分为对照组、LPS组和CurL组(LPS攻毒并添加200 mg/kg日粮姜黄素),每组8头。结果表明,姜黄素降低了断奶仔猪血浆和肝脏中LPS注射诱导的相对肝脏重量增加以及天冬氨酸转氨酶和乳酸脱氢酶浓度(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,姜黄素降低了肝脏中Bcl-2和Bax mRNA的表达,而提高了p53 mRNA水平(p<0.05)。姜黄素抑制了LPS诱导的肝脏中SREBP-1c和SCD-1 mRNA水平的升高。值得注意的是,日粮姜黄素影响了METTL3、METTL14、ALKBH5、FTO和YTHDF2 mRNA的表达,并增加了仔猪肝脏中m⁶A的丰度。总之,姜黄素对LPS诱导的肝损伤和肝脏脂质代谢紊乱的保护作用可能归因于m⁶A RNA甲基化的增加。我们的研究为姜黄素在炎症和代谢疾病期间预防肝损伤的作用提供了机制性见解。

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