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Diabetes. 2014 Nov;63(11):3955-9. doi: 10.2337/db14-0470. Epub 2014 Jun 4.

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.

Author information

1
Department of Neuroscience, Uppsala University, Uppsala, Sweden christian.benedict@neuro.uu.se.
2
Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
3
Department of Public Health and Clinical Medicine and Heart Center, Umeå University, Umeå, Sweden.
4
Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden.
5
Department of Medical Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, U.K.
6
Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
7
Department of Neuroscience, Uppsala University, Uppsala, Sweden.

Abstract

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, self-reported 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 = ∼ 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 = ∼ 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.

PMID:
24898142
DOI:
10.2337/db14-0470
[Indexed for MEDLINE]
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