Fat Mass and Obesity-Associated Gene (FTO) Is Linked to Higher Plasma Levels of the Hunger Hormone Ghrelin and Lower Serum Levels of the Satiety Hormone Leptin in Older Adults
Fat Mass and Obesity-Associated Gene (FTO) Is Linked to Higher Plasma Levels of the Hunger Hormone Ghrelin and Lower Serum Levels of the Satiety Hormone Leptin in Older Adults
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DOI：
10.2337/db14-0470
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发表时间：
2014-11-01
期刊：
影响因子：
7.7
通讯作者：
Schioeth, Helgi B.
中科院分区：
文献类型：
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作者：
Benedict, Christian;Axelsson, Tomas;Schioeth, Helgi B.
脂肪量和肥胖相关基因（FTO）的常见多态性驱动人类肥胖发展的机制知之甚少。使用来自985名老年人（50%为女性）的横断面数据，他们在70岁时参加了乌普萨拉老年人血管系统的前瞻性调查（PIVUS），在禁食过夜后测量了ghrelin和leptin的循环水平。此外，对受试者进行FTO rs 17817449基因分型（AA，n = 345 [35%]; AC/CA，n = 481 [48.8%]; CC，n = 159 [16.1%]）。线性回归分析控制性别，自我报告的体力活动水平，空腹血糖，BMI。发现FTO C风险等位基因的数量与血浆ghrelin水平之间存在正相关（P = 0.005; CC和AA携带者之间的相对血浆ghrelin差异=相似于9%）。相反，血清中的饱腹感增强激素瘦素水平与FTO C风险等位基因的数量呈负相关（P = 0.001; CC和AA携带者之间的相对血清瘦素差异=相似于11%）。在控制腰围时也发现了这些关联。目前的研究结果表明，FTO可能通过将内分泌平衡从饱腹激素瘦素转移到促进饥饿激素饥饿素来促进人类体重增加。
The mechanisms through which common polymorphisms in the fat mass and obesity-associated gene (FTO) drive the development of obesity in humans are poorly understood. Using cross-sectional data from 985 older people (50% females) who participated at age 70 years in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS), circulating levels of ghrelin and leptin were measured after an overnight fast. In addition, subjects were genotyped for FTO rs17817449 (AA, n = 345 [35%]; AC/CA, n = 481 [48.8%]; CC, n = 159 [16.1%]). Linear regression analyses controlling for sex, selfreported physical activity level, fasting plasma glucose, and BMI were used. A positive relationship between the number of FTO C risk alleles and plasma ghrelin levels was found (P = 0.005; relative plasma ghrelin difference between CC and AA carriers = similar to 9%). In contrast, serum levels of the satiety-enhancing hormone leptin were inversely linked to the number of FTO C risk alleles (P = 0.001; relative serum leptin difference between CC and AA carriers = similar to 11%). These associations were also found when controlling for waist circumference. The present findings suggest that FTO may facilitate weight gain in humans by shifting the endocrine balance from the satiety hormone leptin toward the hunger-promoting hormone ghrelin.