FTO is expressed in neurones throughout the brain and its expression is unaltered by fasting.
FTO is expressed in neurones throughout the brain and its expression is unaltered by fasting.
复制标题
DOI：
10.1371/journal.pone.0027968
复制
发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Ashcroft FM
中科院分区：
文献类型：
--
作者：
McTaggart JS;Lee S;Iberl M;Church C;Cox RD;Ashcroft FM
普遍表达的 FTO 基因第一个内含子的单核苷酸多态性与肥胖有关。尽管 FTO 的生理功能尚不清楚，但当 Fto 表达水平受到控制时，食物摄入量往往会发生变化。此外，单独从神经元中删除 FTO 对食物摄入的影响与在所有组织中删除 FTO 相似。这些结果表明 FTO 在大脑中的表达尤为重要。短期（16-48 小时）禁食后下丘脑 Fto mRNA 表达的动态调节已受到相当多的关注，但结果一直存在争议。目前尚无研究量化大脑中 FTO 蛋白水平，并评估短期禁食后其变化。利用免疫组织化学方法，我们发现FTO蛋白在小鼠大脑中广泛表达，并存在于大多数神经元中。利用定量Western blotting和RT-qPCR，我们发现下丘脑、小脑和大脑头端的FTO蛋白和mRNA水平相对均匀，并且大脑中的水平高于下肢骨骼肌中的水平。禁食 18 小时不会改变 FTO 蛋白和 mRNA 的表达模式或水平。我们进一步表明，大多数与食物摄入调节密切相关的 POMC 神经元也表达 FTO，但 FTO 阳性 POMC 神经元的百分比不会因禁食而改变。总之，我们没有发现任何证据表明 Fto/FTO 表达受到短期（18 小时）禁食的调节。因此，由这种食物剥夺引起的饥饿和禁食后食物摄入量增加不太可能是由 Fto/FTO 表达的变化驱动的。 FTO 在神经元中的广泛表达也表明该蛋白的生理学研究不应仅限于下丘脑。
Single-nucleotide polymorphisms in the first intron of the ubiquitously expressed FTO gene are associated with obesity. Although the physiological functions of FTO remain unclear, food intake is often altered when Fto expression levels are manipulated. Furthermore, deletion of FTO from neurones alone has a similar effect on food intake to deletion of FTO in all tissues. These results indicate that FTO expression in the brain is particularly important. Considerable focus has been placed on the dynamic regulation of Fto mRNA expression in the hypothalamus after short-term (16–48 hour) fasting, but results have been controversial. There are no studies that quantify FTO protein levels across the brain, and assess its alteration following short-term fasting. Using immunohistochemistry, we found that FTO protein is widely expressed in mouse brain, and present in the majority of neurones. Using quantitative Western blotting and RT-qPCR we show that FTO protein and mRNA levels in the hypothalamus, cerebellum and rostral brain are relatively uniform, and levels in the brain are higher than in skeletal muscles of the lower limbs. Fasting for 18 hours does not alter the expression pattern, or levels, of FTO protein and mRNA. We further show that the majority of POMC neurones, which are critically involved in food intake regulation, also express FTO, but that the percentage of FTO-positive POMC neurones is not altered by fasting. In summary, we find no evidence that Fto/FTO expression is regulated by short-term (18-hour) fasting. Thus, it is unlikely that the hunger and increased post-fasting food intake caused by such food deprivation is driven by alterations in Fto/FTO expression. The widespread expression of FTO in neurones also suggests that physiological studies of this protein should not be limited to the hypothalamus.
登录
查看更多内容
影响因子：
158.5
作者：
Cecil, Joanne E.;Tavendale, Roger;Palmer, Colin N. A.
通讯作者：
Palmer, Colin N. A.
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
6.9
作者：
Speakman, John R.;Rance, Kellie A.;Johnstone, Alexandra M.
通讯作者：
Johnstone, Alexandra M.
DOI：
10.1126/science.1151710
发表时间：
2007-11-30
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gerken T;Girard CA;Tung YC;Webby CJ;Saudek V;Hewitson KS;Yeo GS;McDonough MA;Cunliffe S;McNeill LA;Galvanovskis J;Rorsman P;Robins P;Prieur X;Coll AP;Ma M;Jovanovic Z;Farooqi IS;Sedgwick B;Barroso I;Lindahl T;Ponting CP;Ashcroft FM;O'Rahilly S;Schofield CJ
通讯作者：
Schofield CJ
影响因子：
56.9
作者：
Frayling, Timothy M.;Timpson, Nicholas J.;McCarthy, Mark I.
通讯作者：
McCarthy, Mark I.