原标题：日粮添加三丁酸甘油酯能减轻宫内发育迟缓的哺乳仔猪的胰岛素抵抗和脂质代谢异常
Dietary Tributyrin Supplementation Attenuates Insulin Resistance and Abnormal Lipid Metabolism in Suckling Piglets with Intrauterine Growth Retardation
作者：Jintian He, Li Dong, Wen Xu, Kaiwen Bai, Changhui Lu, Yanan Wu, Qiang Huang,
Lili Zhang, Tian Wang*
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu, People，s Republic of China
来源：PLoS ONE 10(8): e0136848.
DOI:10.1371/journal.pone.0136848
翻译：肠动力研究院 梁琦
【摘 要】胎儿宫内发育迟缓（IUGR）与机体胰岛素抵抗和脂质代谢异常有关。三丁酸甘油酯（TB）是丁酸的前体物质，可以减轻机体新陈代谢的功能障碍。本文探究了日粮添加三丁酸甘油酯对IUGR新生仔猪胰岛素抵抗和脂代谢的影响。本实验选取8只出生体重正常的新生仔猪（NBW，1.67±0.13kg）和16只IUGR新生仔猪（0.93±0.11kg），均于第7天断奶。实验分为3组，NEW组和IUGR组：均饲喂人工乳；IT组：喂食人工乳+0.1％三丁酸甘油酯;每组8只，雌雄各半。仔猪饲养到第21天时每组挑选6头（雌雄各半）致死并采取血样和肝脏。之后，研究人员对脂代谢相应的参数及mRNA表达量进行测量。实验结果显示，与NEW组仔猪相比，IUGR组仔猪血清胰岛素水平和肝脏中的HOMA-IR，总胆固醇（TC），脂质（TG），非酯化脂肪酸（NEFA）浓度显著升高（P<0.05），而肝脏中酶活性（肝脂酶[HL]，脂蛋白脂酶[LPL]，总脂肪酶[TL]）和糖原浓度显著降低（P <0.05）。在IT组中不难发现补充三丁酸甘油酯能够显著降低仔猪血清中胰岛素浓度，HOMA-IR，低密度脂蛋白胆固醇和高密度脂蛋白胆固醇水平以及肝脏中TG和NEFA的浓度（P <0.05），同时能够显著增加肝脏中酶活性（HL，LPL和TL）和糖原浓度（P <0.05）。实验结果表明，IUGR仔猪肝脏的胰岛素和脂代谢相关信号转导途径（包括转录因子和核因子）mRNA表达水平容易受到影响（P <0.05），但日粮添加三丁酸甘油酯能有效减轻上述代谢紊乱（P <0.05）。总之，通过增加酶活性和上调mRNA表达量，TB补充剂具有减轻IUGR仔猪胰岛素抵抗和脂代谢异常的潜力，从而改善IUGR仔猪早期的代谢效率。
【关键词】哺乳仔猪；宫内发育迟缓；三丁酸甘油酯；肝脏
以下是实验中相关图表
表1：日粮的组成和营养素含量
表2：用于定量实时PCR测定的引物序列
表3：三丁酸甘油酯（TB）对宫内发育迟缓仔猪血清胰岛素和瘦素浓度的影响（第21天）
表4：三丁酸甘油酯（TB）对血清中总胆固醇（TC），甘油三酯（TG），低密度脂蛋白胆固醇（LDL-C），高密度脂蛋白胆固醇（HDL-C）浓度和宫内发育迟缓（IUGR）仔猪肝脏中糖原，TC，TG，非酯化脂肪酸（NEFA）浓度的影响（第21天）
表5：三丁酸甘油酯对宫内发育迟缓（IUGR）仔猪肝脏脂肪酶（HL），脂蛋白脂酶（LPL）和总脂肪酶（TL）活性的影响（第21天）
图1：使用GAPDH作为对照，将INSR，IRS1，PIK3C3和Akt2的mRNA表达量标准化。数据表示为X±SEM，n = 6。SEM，平均值的标准误差。*表示与对照组的差异显著（P <0.05）。NBW：出生体重正常的仔猪，喂食人工乳。IUGR：用人工乳喂食宫内发育迟缓的仔猪;IT：饲喂宫内发育迟缓的仔猪人工乳+0.1％三丁酸甘油酯
图2：使用GAPDH作为对照，将SREBP-1，LXRα，PPARα和FAT / CD36的mRNA表达量标准化。数据表示为X±SEM，n = 6。SEM，平均值的标准误差。*表示与对照组的差异显著（P <0.05）。NBW：出生体重正常的仔猪，喂食人工乳。IUGR：用人工乳喂食宫内发育迟缓的仔猪;IT：饲喂宫内发育迟缓的仔猪人工乳+0.1％三丁酸甘油酯
图3：以GAPDH作为对照，使得FAS，ACCβ，SCD和FABP的mRNA表达量标准化。数据表示为X±SEM，n = 6。SEM，平均值的标准误差。*表示与对照组的差异显著（P <0.05）。NBW：出生体重正常的仔猪，喂食人工乳。IUGR：用人工乳喂食宫内发育迟缓的仔猪;IT：饲喂宫内发育迟缓的仔猪人工乳+0.1％三丁酸甘油酯
Conclusion
总之，本研究结果清楚地表明，患有IUGR的仔猪可导致高胰岛素血症和HOMA-IR水平偏高，这与胰岛素抵抗密切相关。在该研究中观察到IUGR仔猪肝脏中糖代谢和脂代谢紊乱，以及基因表达量的改变。重要的是，这项研究标志性的发现是通过调节mRNA表达和增加酶活性，日粮添加0.1％三丁酸甘油酯可有效减轻IUGR引起的胰岛素抵抗和脂代谢异常。这可能有助于找到一种新的方法，用于早期减轻人类IUGR引起的胰岛素抵抗和代谢异常。
Abstract
Intrauterine growth retardation (IUGR) is associated with insulin resistance and lipid disorder. Tributyrin (TB), a pro-drug of butyrate, can attenuate dysfunctions in body metabolism. In this study, we investigated the effects of TB supplementation on insulin resistance and lipid metabolism in neonatal piglets with IUGR. Eight neonatal piglets with normal birth weight (NBW) and 16 neonatal piglets with IUGR were selected, weaned on the 7th day, and fed basic milk diets (NBW and IUGR groups) or basic milk diets supplemented with 0.1% tributyrin (IT group, IUGR piglets) until day 21 (n = 8). Relative parameters for lipid metabolism and mRNA expression were measured. Piglets with IUGR showed higher (P < 0.05) concentrations of insulin in the serum, higher (P < 0.05) HOMA-IR and total cholesterol, triglycerides (TG), non-esterified fatty acid (NEFA) in the liver, and lower (P < 0.05) enzyme activities (hepatic lipase [HL], lipoprotein lipase [LPL], total lipase [TL]) and concentration of glycogen in the liver than the NBW group. TB supplementation decreased (P < 0.05) the concentrations of insulin, HOMA-IR, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol in the serum, and the concentrations of TG and NEFA in the liver, and increased (P < 0.05) enzyme activities (HL, LPL, and TL) and concentration of glycogen in the liver of the IT group. The mRNA expression for insulin signal transduction pathway and hepatic lipogenic pathway (including transcription factors and nuclear factors) was significantly (P < 0.05) affected in the liver by IUGR, which was efficiently (P < 0.05) attenuated by diets supplemented with TB. TB supplementation has therapeutic potential for attenuating insulin resistance and abnormal lipid metabolism in IUGR piglets by increasing enzyme activities and upregulating mRNA expression, leading to an early improvement in the metabolic efficiency of IUGR piglets.
Conclusion
In conclusion, our findings clearly demonstrated that piglets with IUGR can lead to the hyperinsulinism and high HOMA-IR, which were closely linked to the insulin resistance. Disorder of glycometabolism and lipid catabolism in the liver of IUGR piglets, and with alterations for gene expression were observed in this study. Importantly, the most remarkable finding of this study was that diet supplementation with 0.1% TB could efficiently attenuate insulin resistance and abnormal levels of lipid metabolism caused by IUGR through regulation of mRNA expression and increasing enzyme activity, which could be helpful in finding a new strategy for early attenuation of insulin resistance and metabolic abnormality caused by IUGR in humans.
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