Preliminary findings on the influence of FTO rs9939609 and MC4R rs17782313 polymorphisms on resting energy expenditure, leptin and thyrotropin levels in obese non-morbid premenopausal women

Abstract

Given that leptin, ghrelin and thyrotropin play a major role in the regulation of resting energy expenditure (REE) and that the FTO rs9939609 and the MC4R rs17782313 polymorphisms have been proposed to affect energy homeostasis, we hypothesized that both polymorphisms are associated with REE and that these relationships can be mediated by leptin, ghrelin and thyrotropin in obesity. Therefore, the present study aimed to examine the relationships between FTO rs9939609 and the MC4R rs17782313 with REE, leptin, ghrelin and thyrotropin levels in obese women. The study comprised 77 obese (body mass index 34.0 ± 2.8 kg/m(2)) women (age 36.7 ± 7 years). We measured body composition by dual-energy X-ray absorptiometry and REE by indirect calorimetry. We analysed fasting leptin, ghrelin and thyrotropin levels and the ratio of leptin to fat mass was calculated. Genotype distributions of the polymorphisms did not deviate from Hardy-Weinberg expectations (P values >0.2). Women carrying the A allele of the FTO rs9939609 had lower REE (1,580 ± 22 vs. 1,739 ± 35 kcal/day, P < 0.001) and higher leptin to fat mass ratio (1.33 ± 0.05 vs. 1.13 ± 0.08 ng/ml kg, P < 0.05) and thyrotropin levels (1.93 ± 0.10 vs. 1.53 ± 0.16 μU/ml, P < 0.05) regardless of age and body mass index. We found no significant influence of the MC4R rs17782313 on energy metabolism or biochemical variables. Our findings confirm that the A allele of the FTO rs9939609 is associated with lower REE and increased plasma leptin levels. We also found an association between the FTO rs9939609 and thyrotropin, suggesting the possible influence of FTO in the hypothalamic-pituitary-thyroid axis as a potential mechanism of the increased adiposity.

Association of FTO rs9939609 polymorphism with serum leptin, insulin, adiponectin, and lipid profile in overweight adults

“…It is plausible that FTO risk allele can increase the level of serum leptin via increasing the BF and BMI. FTO rs9939609 polymorphism is reported to be associated with REE [29]. The leptin also plays an important role in the regulation of resting energy expenditure (REE).…”

Establishing a genetic link between FTO and VDR gene polymorphisms and obesity in the Emirati population

“…Moreover, a multicenter trial in Europe showed strong association with severe obesity in bariatric patients ( p = 9.2 × 10 − 8 , OR = 1.47) as well [ 35 ]. The association of the risk allele “A” with higher leptin to fat mass ratio, higher levels of thyrotropin and lower resting energy expenditure is a likely explanation for its predisposition to increased obesity risk [ 36 ]. However, there have been studies in African American and Chinese Han population that show no association of the “A” allele with higher BMI risk [ 27 , 37 ].…”

Role of FTO in Adipocyte Development and Function: Recent Insights

“…FTO risk alleles have been associated with changes in circulating levels of the appetite regulating hormones leptin and ghrelin. Several papers have shown that FTO risk allele is associated with increased circulating leptin levels [ 40 – 47 ]. However, this association appears to be mediated via increased adiposity, as in several studies the association disappears when correcting for BMI [ 42 , 44 – 46 ].…”