Background After meal ingestion, a series of coordinated hormone responses occur concomitantly with changes in perceived appetite. It is not known whether interindividual variability in appetite exists in response to a meal. Objectives The aim of this study was to 1) assess the reproducibility of appetite responses to a meal; 2) quantify individual differences in responses; and 3) explore any moderating influence of the fat mass and obesity associated (FTO) gene. Methods Using a replicated crossover design, 18 healthy men (mean ± SD age: 28.5 ± 9.8 y; BMI: 27.0 ± 5.0 kg/m2) recruited according to FTO genotype (9 AA, 9 TT) completed 2 identical control and 2 identical standardized meal conditions (5025 kJ) in randomized sequences. Perceived appetite and plasma acylated ghrelin, total peptide YY (PYY), insulin, and glucose concentrations were measured before and after interventions as primary outcomes. Interindividual differences were explored using Pearson's product-moment correlations between the first and second replicates of the control-adjusted meal response. Within-participant covariate-adjusted linear mixed models were used to quantify participant-by-condition and genotype-by-condition interactions. Results The meal suppressed acylated ghrelin and appetite perceptions [standardized effect size (ES): 0.18–4.26] and elevated total PYY, insulin, and glucose (ES: 1.96–21.60). For all variables, SD of change scores was greater in the meal than in the control conditions. Moderate-to-large positive correlations were observed between the 2 replicates of control-adjusted meal responses for all variables (r = 0.44–0.86, P ≤ 0.070). Participant-by-condition interactions were present for all variables (P ≤ 0.056). FTO genotype-by-condition interactions were nonsignificant (P ≥ 0.19) and treatment effect differences between genotype groups were small (ES ≤ 0.27) for all appetite parameters. Conclusions Reproducibility of postprandial appetite responses is generally good. True interindividual variability is present beyond any random within-subject variation in healthy men but we detected no moderation by the FTO genotype. These findings highlight the importance of exploring individual differences in appetite for the prevention and treatment of obesity. This trial was registered at clinicaltrials.gov as NCT03771690.

This study investigated the role of IL-1β-511 (rs16944), TLR4-896 (rs4986790) and TNF-α-308 (rs1800629) polymorphisms in type 2 diabetes mellitus (T2DM) among an endogamous Northern Indian population. Four hundred fourteen participants (204 T2DM patients and 210 nondiabetic controls) were genotyped for IL-1β-511, TLR4-896 and TNF-α-308 loci. The C allele of IL-1β-511 was shown to increase T2DM susceptibility by 75% (OR: 1.75 [CI 1.32-2.33]). Having two parents affected by T2DM increased susceptibility by 5.7 times (OR: 5.693 [CI 1.431-22.648]). In this study, we have demonstrated a conclusive association with IL-1β-511 locus and IL-1β-511-TLR4-896 diplotype (CC-AA) and T2DM, which warrants further comprehensive analyses in larger cohorts.

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.

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