Pausova Zdenka, Syme Catriona, Abrahamowicz Michal, Xiao Yongling, Leonard Gabriel T, Perron Michel, Richer Louis, Veillette Suzanne, Smith George Davey, Seda Ondrej, Tremblay Johanne, Hamet Pavel, Gaudet Daniel, Paus Tomas
Brain and Body Centre, University of Nottingham, Nottingham, United Kingdom.
Circ Cardiovasc Genet. 2009 Jun;2(3):260-9. doi: 10.1161/CIRCGENETICS.109.857359. Epub 2009 Mar 31.
FTO is the first gene established as contributing to common forms of obesity. The gene is highly expressed in the hypothalamus and is thought to mediate this effect through its influence on energy homeostasis. The hypothalamus, however, also regulates blood pressure (BP). Therefore, we investigated whether the FTO-risk variant is associated not only with increased adiposity but also with elevated BP and whether the latter may be mediated, in part, by increased sympathetic modulation of vasomotor tone.
The primary study was carried out in 485 adolescents recruited from a French Canadian founder population who underwent detailed body-composition and cardiovascular phenotyping. Body fat was examined with MRI, bioimpedance, and anthropometry. BP was recorded beat to beat at rest and during physical and mental challenges. Sympathetic modulation of vasomotor tone was assessed with power spectral analysis of BP. We found that individuals with the FTO-risk genotype compared with those without it demonstrate greater adiposity, including the amount of intra-abdominal fat (by 38%). They also showed higher systolic BP throughout the entire protocol, with a maximum difference during a mental stress (6.4 [1.5 to 11.3] mm Hg). The difference in BP was accompanied by elevated index of sympathetic modulation of vasomotor tone. A replication in an independent sample of adults from the same founder population confirmed the association between FTO and BP.
These results suggest that, in a French Canadian founder population, FTO may increase not only risk for obesity, as demonstrated in other populations, but also for hypertension. The latter may be related, at least in part, to the regulation of sympathetic vasomotor tone.
FTO是首个被证实与常见肥胖类型相关的基因。该基因在下丘脑中高度表达，被认为通过影响能量平衡来介导这种作用。然而，下丘脑也调节血压（BP）。因此，我们研究了FTO风险变异是否不仅与肥胖增加有关，还与血压升高有关，以及后者是否可能部分由血管运动张力的交感神经调节增加所介导。
主要研究在485名从法裔加拿大创始人群中招募的青少年中进行，这些青少年接受了详细的身体成分和心血管表型分析。通过MRI、生物电阻抗和人体测量法检查身体脂肪。在静息状态以及身体和精神应激期间逐搏记录血压。通过血压功率谱分析评估血管运动张力的交感神经调节。我们发现，与无FTO风险基因型的个体相比，有该基因型的个体表现出更高的肥胖程度，包括腹部脂肪量（增加38%）。在整个实验过程中，他们的收缩压也更高，在精神应激期间差异最大（6.4 [1.5至11.3] mmHg）。血压差异伴随着血管运动张力交感神经调节指数的升高。在来自同一创始人群的独立成人样本中进行的重复研究证实了FTO与血压之间的关联。
这些结果表明，在法裔加拿大创始人群中，FTO可能不仅像在其他人群中所证实的那样增加肥胖风险，还增加高血压风险。后者可能至少部分与交感神经血管运动张力的调节有关。
