OBJECTIVETo examine the longitudinal association of fat massand obesity-associated (FTO) variant with obesity, circulating adipokine levels, and FTO expression in various materials from human and mouse. RESEARCH DESIGN AND METHODSWe genotyped rs9939609 in 2,287 men and 3,520 women from two prospective cohorts. Plasma adiponectin and leptin were measured in a subset of diabetic men (n = 854) and women (n = 987). Expression of FTO was tested in adipocytes from db/db mice and mouse macrophages. RESULTSWe observed a trend toward decreasing associations between rs9939609 and BMI at older age (65 years) in men, whereas the associations were constant across different age groups in women. In addition, the single nucleotide polymorphism (SNP) rs9939609 was associated with lower plasma adiponectin (loge means, 1.82 0.04, 1.73 0.03, and 1.68 0.05 for TT, TA, and AA genotypes, respectively; P for trend = 0.02) and leptin (loge means, 3.56 0.04, 3.63 0.04, and 3.70 0.06; P for trend = 0.06) in diabetic women. Adjustment for BMI attenuated the associations. FTO gene was universally expressed in human and mice tissues, including adipocytes. In an ancillary study of adipocytes from db/db mice, FTO expression was 50% lower than in those from wild-type mice. CONCLUSIONSThe association between FTO SNP rs9939609 and obesity risk may decline at older age. The variant affects circulating adiponectin and leptin levels through the changes in BMI. In addition, the expression of FTO gene was reduced in adipocytes from db/db mice.
Qi, L., Kang, K., Zhang, C., Van Dam, R. M., Kraft, P., Hunter, D., … Hu, F. B. (2008). Fat Mass–and Obesity-Associated (FTO) Gene Variant Is Associated With Obesity. Diabetes, 57(11), 3145–3151. https://doi.org/10.2337/db08-0006