Exploration of associations between the FTO rs9939609 genotype, fasting and postprandial appetite-related hormones and perceived appetite in healthy men and women

Abstract

Background: The fat mass and obesity-associated gene (FTO) rs9939609 A-allele has been associated with obesity risk. Although the exact mechanisms involved remain unknown, the FTO rs9939609 A-allele has been associated with an impaired postprandial suppression of appetite. Objectives: To explore the influence of FTO rs9939609 genotype on fasting and postprandial appetite-related hormones and perceived appetite in a heterogeneous sample of men and women. Design: 112 healthy men and women aged 18-50-years-old completed three laboratory visits for the assessment of FTO rs9939609 genotype, body composition, aerobic fitness, resting metabolic rate, visceral adipose tissue, liver fat, fasting leptin, and fasting and postprandial acylated ghrelin, total PYY, insulin, glucose and perceived appetite. Participants wore accelerometers for seven consecutive days for the assessment of physical activity and sedentary behaviour. Multivariable general linear models quantified differences between FTO rs9939609 groups for fasting and postprandial appetite outcomes, with and without the addition of a priori selected physiological and behavioural covariates. Sex-specific univariable Pearson's correlation coefficients were quantified between the appetite-related outcomes and individual characteristics. Results: 95% confidence intervals for mean differences between FTO rs9939609 groups overlapped zero in unadjusted and adjusted general linear models for all fasting (P≥0.28) and postprandial (P≥0.19) appetite-related outcomes. Eta 2 values for explained variance attributable to FTO rs9939609 were <5% for all outcomes. An exploratory correlation matrix indicated that associations between fasting and postprandial acylated ghrelin, total PYY and general or abdominal adiposity were also small (r =-0.23 to 0.15, P≥0.09). Fasting leptin, glucose and insulin and postprandial insulin concentrations were associated with adiposity outcomes (r = 0.29 to 0.81, P≤0.033). Conclusions: Associations between the FTO rs9939609 genotype and fasting or postprandial appetite-related outcomes were weak in healthy men and women.

The fat mass and obesity-associated (FTO) gene allele rs9939609 and glucose tolerance, hepatic and total insulin sensitivity, in adults with obesity

“…For our participants who had severe obesity but were otherwise clinically healthy, it was difficult from meal test data to compare capacities for insulin secretion when blood glucose levels were as expected in subjects without diabetes. Our results are thus in line with those of Goltz et al [48]. They used a test meal with a higher energy and carbohydrate content than ours, yet did not detect obvious genotype effects from FTO rs9939609 on postprandial glucose and insulin responses.…”

“…While most human studies examining the effect of the FTO rs9939609 risk allele on glucose tolerance and IS have assessed only fasting glucose and insulin levels, few have measured postprandial glucose and insulin responses [10,49,50]. To our knowledge, only one study has assessed postprandial blood glucose and insulin responses to a real life-mimicking meal [48], while no studies have assessed the association between the FTO risk allele and EGP in vivo. There are strengths and limitations to our study.…”

Impact of the FTO Gene Variation on Appetite and Fat Oxidation in Young Adults

“…It has been proposed that the AA allele might alter the suppression of postprandial appetite, increasing the preference for high-calorie dense foods, stimulating hyperphagia and modulating satiety in the hypothalamus [6,10]. Nevertheless, there is still controversy to this proposal because other authors have not found any significant differences in the regulation of appetite of the FTO rs9939609 gene [11]; therefore, other physiological explanations should be searched for. One physiological mechanism in which the FTO rs9939609 gene could modulate fat mass is through the alteration of energetic metabolism and fat oxidation [12,13].…”

Associations of objectively measured physical activity, sedentary time and cardiorespiratory fitness with adipose tissue insulin resistance and ectopic fat

“…We performed a pooled analysis of data collected across two separate experimental studies; a cross-sectional study [ 26 ] and an acute cross-over study [ 27 ] conducted at Loughborough University. Both studies were conducted in the same laboratory, used identical protocols/ Standard Operating Procedures, and analytical approaches.…”