Resveratrol Attenuates High-Fat Diet Induced Hepatic Lipid Homeostasis Disorder and Decreases m(6)A RNA Methylation.
Resveratrol Attenuates High-Fat Diet Induced Hepatic Lipid Homeostasis Disorder and Decreases m(6)A RNA Methylation.
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白藜芦醇可减轻高脂饮食引起的肝脂质稳态紊乱并减少 m(6)A RNA 甲基化
DOI：
10.3389/fphar.2020.568006
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发表时间：
2020
影响因子：
5.6
通讯作者：
Zhong X
中科院分区：
文献类型：
--
作者：
Wu J;Li Y;Yu J;Gan Z;Wei W;Wang C;Zhang L;Wang T;Zhong X
目的：N6-甲基腺苷（m6 A）mRNA甲基化受饮食因素影响，与脂代谢相关，但白藜芦醇对脂代谢的调节作用是否与m6 A mRNA甲基化有关尚不清楚。本研究旨在探讨白藜芦醇对小鼠肝脏脂质代谢和m6 A RNA甲基化的影响。 研究方法：将24只雄性小鼠随机分为LFD（低脂饮食）、LFDR（低脂饮食+白藜芦醇）、HFD（高脂饮食）和HFDR（高脂饮食+白藜芦醇）组，每组6只，持续12周。处死前测量小鼠的最终体重。处死时收集围体脂肪、腹部和附睾脂肪、肝脏组织和血清并进行分析。简言之，评估小鼠表型、脂质代谢指数和肝脏中的m6 A修饰。 结果如下：与HFD组相比，膳食白藜芦醇补充剂降低了高脂肪暴露小鼠的体重和相对腹部、附睾和围血脂肪重量;然而，白藜芦醇显著增加了给予HFD的小鼠的平均每日摄食量。血清低密度脂蛋白胆固醇（LDL），肝脏总胆固醇（TC），和三酰甘油（TAG）的数量显着降低白藜芦醇补充。此外，白藜芦醇显著提高过氧化物酶体增殖物激活受体α（PPARα）、过氧化物酶体增殖物激活受体β/δ（PPARβ/δ）、细胞色素P450、家族4、亚家族a、多肽10/14（CYP 4A 10/14）、酰基辅酶A氧化酶1（ACOX 1）和脂肪酸结合蛋白4（FABP 4）mRNA，并抑制肝脏中酰基辅酶A羧化酶（ACC）mRNA水平。此外，HFD中的白藜芦醇增加了小鼠肝脏中甲基转移酶样3（Methyltransferase like 3，胃L3）、alkB同源物5（alkB homolog 5，ALKBH 5）、脂肪量和肥胖相关蛋白（fat mass and obesity associated protein，FTO）和YTH结构域家族2（YTHDF 2）的转录水平，而降低了YTH结构域家族3（YTHDF 3）和m6 A丰度的水平。 结论：白藜芦醇对高脂饮食小鼠脂代谢紊乱的改善作用可能是通过降低m6 A RNA甲基化水平和增加PPARα mRNA表达而实现的，为白藜芦醇改善小鼠脂代谢紊乱的作用机制提供了理论依据。
Purpose: N 6-methyladenosine (m6A) mRNA methylation is affected by dietary factors and associated with lipid metabolism; however, whether the regulatory role of resveratrol in lipid metabolism is involved in m6A mRNA methylation remains unknown. Here, the objective of this study was to investigate the effect of resveratrol on hepatic lipid metabolism and m6A RNA methylation in the liver of mice. Methods: A total of 24 male mice were randomly allocated to LFD (low-fat diet), LFDR (low-fat diet + resveratrol), HFD (high-fat diet), and HFDR (high-fat diet + resveratrol) groups for 12 weeks (n = 6/group). Final body weight of mice was measured before sacrificing. Perirhemtric fat, abdominal and epididymal fat, liver tissues, and serum were collected at sacrifice and analyzed. Briefly, mice phenotype, lipid metabolic index, and m6A modification in the liver were assessed. Results: Compared to the HFD group, dietary resveratrol supplementation reduced the body weight and relative abdominal, epididymal, and perirhemtric fat weight in high-fat-exposed mice; however, resveratrol significantly increased average daily feed intake in mice given HFD. The amounts of serum low-density lipoprotein cholesterol (LDL), liver total cholesterol (TC), and triacylglycerol (TAG) were significantly decreased by resveratrol supplementation. In addition, resveratrol significantly enhanced the levels of peroxisome proliferator-activated receptor alpha (PPARα), peroxisome proliferator-activated receptor beta/delta (PPARβ/δ), cytochrome P450, family 4, subfamily a, polypeptide 10/14 (CYP4A10/14), acyl-CoA oxidase 1 (ACOX1), and fatty acid-binding protein 4 (FABP4) mRNA and inhibited acyl-CoA carboxylase (ACC) mRNA levels in the liver. Furthermore, the resveratrol in HFD increased the transcript levels of methyltransferase like 3 (METTL3), alkB homolog 5 (ALKBH5), fat mass and obesity associated protein (FTO), and YTH domain family 2 (YTHDF2), whereas it decreased the level of YTH domain family 3 (YTHDF3) and m6A abundance in mice liver. Conclusion: The beneficial effect of resveratrol on lipid metabolism disorder under HFD may be due to decrease of m6A RNA methylation and increase of PPARα mRNA, providing mechanistic insights into the function of resveratrol in alleviating the disturbance of lipid metabolism in mice.
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影响因子：
4.4
作者：
Fu S;Lv R;Wang L;Hou H;Liu H;Shao S
通讯作者：
Shao S
n（6） - 甲基腺苷依赖性RNA结构开关调节RNA蛋白质相互作用。
影响因子：
64.8
作者：
Liu, Nian;Dai, Qing;Zheng, Guanqun;He, Chuan;Parisien, Marc;Pan, Tao
通讯作者：
Pan, Tao
RNA 中的 N6-甲基-腺苷 (m6A)：具有新表观遗传功能的旧修饰
影响因子：
9.5
作者：
Niu, Yamei;Zhao, Xu;Wu, Yong-Sheng;Li, Ming-Ming;Wang, Xiu-Jie;Yang, Yun-Gui
通讯作者：
Yang, Yun-Gui
DOI：
10.1152/ajpgi.90358.2008
发表时间：
2008-10-01
影响因子：
4.5
作者：
Ajmo, Joanne M.;Liang, Xiaomei;You, Min
通讯作者：
You, Min
影响因子：
5.8
作者：
Fellous, Tariq;De Maio, Fabrizia;Iannotti, Fabio Arturo
通讯作者：
Iannotti, Fabio Arturo