Evidence against a beneficial effect of irisin in humans.
Evidence against a beneficial effect of irisin in humans.
复制标题
DOI：
10.1371/journal.pone.0073680
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Eckel J
中科院分区：
文献类型：
--
作者：
Raschke S;Elsen M;Gassenhuber H;Sommerfeld M;Schwahn U;Brockmann B;Jung R;Wisløff U;Tjønna AE;Raastad T;Hallén J;Norheim F;Drevon CA;Romacho T;Eckardt K;Eckel J
棕色脂肪组织作为治疗肥胖和代谢疾病的潜在靶点引起了人们的兴趣。鸢尾素是一种新发现的由骨骼肌分泌的激素，可增强白色脂肪细胞的褐变，通过增加小鼠的能量消耗来改善全身代谢。鸢尾素的发现提高了人们对其治疗代谢疾病的潜力的期望。然而，鸢尾素对人体的作用尚不清楚。对基因组 DNA、mRNA 和表达序列标签的分析表明，编码鸢尾素前体的基因 FNDC5 存在于啮齿类动物和大多数灵长类动物中，但在人类中显示保守起始密码子 ATG 突变为 ATA。与具有 ATG 的人 FNDC5 相比，用以 ATA 作为起始密码子的人 FNDC5 构建体转染的 HEK293 细胞仅产生 1% 的全长蛋白质。此外，在体外，电脉冲刺激引起的人原代肌管收缩可诱导 PGC1α mRNA 表达显着增加。然而，FNDC5 mRNA 水平没有改变。两项不同人体运动研究的肌肉活检中 FNDC5 mRNA 表达并未因耐力或力量训练而改变。当与骨形态发生蛋白（BMP）7一起孵育时，从人皮下脂肪组织中分离的前脂肪细胞表现出向人脂肪细胞的分化，但重组FNDC5和鸢尾素均无效。总之，我们的研究结果表明，在小鼠中观察到的鸢尾素的有益作用不太可能转化为人类。
Brown adipose tissue has gained interest as a potential target to treat obesity and metabolic diseases. Irisin is a newly identified hormone secreted from skeletal muscle enhancing browning of white fat cells, which improves systemic metabolism by increasing energy expenditure in mice. The discovery of irisin raised expectations of its therapeutic potential to treat metabolic diseases. However, the effect of irisin in humans is unclear. Analyses of genomic DNA, mRNA and expressed sequence tags revealed that FNDC5, the gene encoding the precursor of irisin, is present in rodents and most primates, but shows in humans a mutation in the conserved start codon ATG to ATA. HEK293 cells transfected with a human FNDC5 construct with ATA as start codon resulted in only 1% full-length protein compared to human FNDC5 with ATG. Additionally, in vitro contraction of primary human myotubes by electrical pulse stimulation induced a significant increase in PGC1α mRNA expression. However, FNDC5 mRNA level was not altered. FNDC5 mRNA expression in muscle biopsies from two different human exercise studies was not changed by endurance or strength training. Preadipocytes isolated from human subcutaneous adipose tissue exhibited differentiation to brite human adipocytes when incubated with bone morphogenetic protein (BMP) 7, but neither recombinant FNDC5 nor irisin were effective. In conclusion, our findings suggest that it is rather unlikely that the beneficial effect of irisin observed in mice can be translated to humans.
登录
查看更多内容
DOI：
10.1016/j.numecd.2012.01.013
发表时间：
2013-06-01
影响因子：
3.9
作者：
De Matteis, R.;Lucertini, F.;Cuppini, R.
通讯作者：
Cuppini, R.
影响因子：
3
作者：
Kochetov AV;Palyanov A;Titov II;Grigorovich D;Sarai A;Kolchanov NA
通讯作者：
Kolchanov NA
影响因子：
5.5
作者：
Haugen, Fred;Norheim, Frode;Drevon, Christian A.
通讯作者：
Drevon, Christian A.
影响因子：
3
作者：
Gjelstad, I. M. F.;Haugen, F.;Drevon, C. A.
通讯作者：
Drevon, C. A.
影响因子：
7.1
作者：
Lyon, HN;Hirschhorn, JN
通讯作者：
Hirschhorn, JN