Excessive fuel availability amplifies the FTO-mediated obesity risk: results from the TUEF and Whitehall II studies

Abstract

Variation in FTO is the most important common genetic determinant of body weight. Altered energy metabolism could underlie this association. We hypothesized that higher circulating glucose or triglycerides can amplify the FTO impact on BMI. In 2671 subjects of the TUEF study, we investigated the interaction effect of fasting glucose and triglyceride levels with rs9939609 in FTO on BMI. We analysed the same interaction effect by longitudinally utilizing mixed effect models in the prospective Whitehall II study. In TUEF, we detected an interaction effect between fasting glucose and fasting triglycerides with rs9939609 on BMI (p = 0.0005 and p = 5 × 10−7, respectively). The effect size of one risk allele was 1.4 ± 0.3 vs. 2.2 ± 0.44 kg/m² in persons with fasting glucose levels below and above the median, respectively. Fasting triglycerides above the median increased the per-allele effect from 1.4 ± 0.3 to 1.7 ± 0.4 kg/m2. In the Whitehall II study, body weight increased by 2.96 ± 6.5 kg during a follow-up of 13.5 ± 4.6 yrs. Baseline fasting glucose and rs9939609 interacted on weight change (p = 0.009). Higher fasting glucose levels may amplify obesity-risk in FTO carriers and lead to an exaggerated weight gain over time. Since weight gain perpetuates metabolic alterations, this interplay may trigger a vicious circle that leads to obesity and diabetes.

Risk-stratified lifestyle intervention to prevent type 2 diabetes

“…Insulinogenic index (arbitrary units) as marker for insulin secretion is shown as hyperbolic function of insulin sensitivity (insulin sensitivity index, arbitrary units, unadjusted values). Subjects with normal glucose tolerance (NGT, age 18-50 years) from the German TUEF study (40) were used to compute the hyperbolic function (n=1421). The arrows represent baseline values (origin) and values after 12 months of intervention (end) in the study arms.…”

Az elhízás, a 2-es típusú diabetes és a daganatok közötti genetikai összefüggések egy perspektívája

“…A többféle gén számos allélvariánsa, az életmódi és egyéb környezeti faktorok (például étrend, fizikai aktivitás, negatív stressz, dohányzás, környezetszennyezés) változásai azonban együttesen már jelentős szerepet játszhatnak az adott betegség klinikai megjelenésében. Mindezen összefüggések a "gén-gén" és a "gén-környezet" interakció modellek alapját képezik [6,[8][9][10].…”

RNA N6-Methyladenosine in Cancer Metastasis: Roles, Mechanisms, and Applications

“…More interestingly, some studies found that METTL14 improves its translation efficiency without changing the mRNA expression level; that is, the target mRNA abundance remains unchanged ( 145 ). Preceding studies suggested that FTO mediates changes in energy metabolism to regulate weight and growth in adults ( 146 , 147 ). Recent studies found that the expression of FTO is upregulated in human breast cancer.…”