Gebeyew Kefyalew, Yang Chao, Mi Hui, Cheng Yan, Zhang Tianxi, Hu Fan, Yan Qiongxian, He Zhixiong, Tang Shaoxun, Tan Zhiliang
CAS Key Laboratory for Agro-Ecological Processes in Subtropical Region, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Changsha, 410125, Hunan, China.
University of Chinese Academy of Science, Beijing, 100049, China.
J Anim Sci Biotechnol. 2022 Jul 13;13(1):85. doi: 10.1186/s40104-022-00733-z.
Methionine or lysine has been reported to influence DNA methylation and fat metabolism, but their combined effects in N6-methyl-adenosine (mA) RNA methylation remain unclarified. The combined effects of rumen-protected methionine and lysine (RML) in a low-protein (LP) diet on lipid metabolism, mA RNA methylation, and fatty acid (FA) profiles in the liver and muscle of lambs were investigated. Sixty-three male lambs were divided into three treatment groups, three pens per group and seven lambs per pen. The lambs were fed a 14.5% crude protein (CP) diet (adequate protein [NP]), 12.5% CP diet (LP), and a LP diet plus RML (LP + RML) for 60 d.
The results showed that the addition of RML in a LP diet tended to lower the concentrations of plasma leptin (P = 0.07), triglyceride (P = 0.05), and non-esterified FA (P = 0.08). Feeding a LP diet increased the enzyme activity or mRNA expression of lipogenic enzymes and decreased lipolytic enzymes compared with the NP diet. This effect was reversed by supplementation of RML with a LP diet. The inclusion of RML in a LP diet affected the polyunsaturated fatty acids (PUFA), n-3 PUFA, and n-6 PUFA in the liver but not in the muscle, which might be linked with altered expression of FA desaturase-1 (FADS1) and acetyl-CoA carboxylase (ACC). A LP diet supplemented with RML increased (P < 0.05) total mA levels in the liver and muscle and were accompanied by decreased expression of fat mass and obesity-associated protein (FTO) and alkB homologue 5 (ALKBH5). The mRNA expressions of methyltransferase-like 3 (METTL3) and methyltransferase-like 14 (METTL14) in the LP + RML diet group were lower than those in the other two groups. Supplementation of RML with a LP diet affected only liver YTH domain family (YTHDF2) proteins (P < 0.05) and muscle YTHDF3 (P = 0.09), which can be explained by limited mA-binding proteins that were mediated in mRNA fate.
Our findings showed that the inclusion of RML in a LP diet could alter fat deposition through modulations of lipogenesis and lipolysis in the liver and muscle. These changes in fat metabolism may be associated with the modification of mA RNA methylation. A systematic graph illustrates the mechanism of dietary methionine and lysine influence on lipid metabolism and MA. The green arrow with triangular heads indicates as activation and brown-wine arrows with flat heads indicates as suppression.
据报道，蛋氨酸或赖氨酸会影响DNA甲基化和脂肪代谢，但它们在N6-甲基腺苷（m⁶A）RNA甲基化中的联合作用仍不清楚。本研究探讨了低蛋白（LP）日粮中瘤胃保护性蛋氨酸和赖氨酸（RML）对羔羊肝脏和肌肉脂质代谢、m⁶A RNA甲基化及脂肪酸（FA）谱的联合影响。将63只雄性羔羊分为三个处理组，每组3个圈舍，每个圈舍7只羔羊。给羔羊饲喂14.5%粗蛋白（CP）日粮（适宜蛋白[NP]）、12.5% CP日粮（LP）和LP日粮加RML（LP + RML）60天。
结果表明，LP日粮中添加RML有降低血浆瘦素（P = 0.07）、甘油三酯（P = 0.05）和非酯化脂肪酸（P = 0.08）浓度的趋势。与NP日粮相比，饲喂LP日粮会增加生脂酶的酶活性或mRNA表达，并降低脂解酶活性。LP日粮添加RML可逆转这种影响。LP日粮中添加RML会影响肝脏中的多不饱和脂肪酸（PUFA）、n-3 PUFA和n-6 PUFA，但不影响肌肉中的这些脂肪酸，这可能与脂肪酸去饱和酶-1（FADS1）和乙酰辅酶A羧化酶（ACC）表达的改变有关。补充RML的LP日粮可提高（P < 0.05）肝脏和肌肉中的总m⁶A水平，并伴随脂肪量和肥胖相关蛋白（FTO）及alkB同源物5（ALKBH5）表达的降低。LP + RML日粮组中甲基转移酶样3（METTL3）和甲基转移酶样14（METTL14）的mRNA表达低于其他两组。LP日粮补充RML仅影响肝脏YTH结构域家族（YTHDF2）蛋白（P < 0.05）和肌肉YTHDF3（P = 0.09），这可以由mRNA命运中介导的有限m⁶A结合蛋白来解释。
我们的研究结果表明，LP日粮中添加RML可通过调节肝脏和肌肉中的脂肪生成和脂肪分解来改变脂肪沉积。脂肪代谢的这些变化可能与m⁶A RNA甲基化的改变有关。一个系统图表说明了日粮蛋氨酸和赖氨酸对脂质代谢和m⁶A的影响机制。带三角形头的绿色箭头表示激活，带平头的棕褐色箭头表示抑制。
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