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

BACKGROUND/OBJECTIVES: Inadequate movement, excess adiposity, and insulin resistance augment cardiometabolic risk. This study examined the associations of objectively measured moderate-to-vigorous intensity physical activity (MVPA), sedentary time and cardiorespiratory fitness (CRF), with adipose tissue insulin resistance and ectopic fat. METHODS: Data were combined from two previous experimental studies with community volunteers (n = 141, male = 60%, median (interquartile range) age = 37 (19) years, body mass index (BMI) = 26.1 (6.3) kg·m-2). Adipose tissue insulin resistance was assessed using the adipose tissue insulin resistance index (Adipo-IR); whilst magnetic resonance imaging (MRI) was used to measure liver, visceral (VAT) and subcutaneous abdominal adipose tissue (ScAT). Sedentary time and MVPA were measured via an ActiGraph GT3X+ accelerometer. Generalized linear models examined the association of CRF, MVPA, and sedentary time with Adipo-IR and fat depots. Interaction terms explored the moderating influence of age, sex, BMI and CRF. RESULTS: After controlling for BMI and cardiometabolic variables, sedentary time was positively associated with Adipo-IR (ß = 0.68 AU [95%CI = 0.27 to 1.10], P < 0.001). The association between sedentary time and Adipo-IR was moderated by age, CRF and BMI; such that it was stronger in individuals who were older, had lower CRF and had a higher BMI. Sedentary time was also positively associated with VAT (ß = 0.05 L [95%CI = 0.01 to 0.08], P = 0.005) with the relationship being stronger in females than males. CRF was inversely associated with VAT (ß = -0.02 L [95%CI = -0.04 to -0.01], P = 0.003) and ScAT (ß = -0.10 L [95%CI = -0.13 to -0.06], P < 0.001); with sex and BMI moderating the strength of associations with VAT and ScAT, respectively. CONCLUSIONS: Sedentary time is positively associated with adipose tissue insulin resistance which regulates lipogenesis and lipolysis. CRF is independently related to central fat storage which is a key risk factor for cardiometabolic disease.

True Interindividual Variability Exists in Postprandial Appetite Responses in Healthy Men But Is Not Moderated by the FTO Genotype.

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.

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

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. Eta2 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.

Circulating leukocyte cell-derived chemotaxin 2 and fibroblast growth factor 21 are negatively associated with cardiorespiratory fitness in healthy volunteers.

Leukocyte cell-derived chemotaxin-2 (LECT2) and fibroblast growth factor 21 (FGF21) are hepatokines that are regulated by energy balance and mediate insulin sensitivity and glycaemic control. This cross-sectional study examined the independent associations of cardiorespiratory fitness (CRF), moderate-to-vigorous intensity physical activity (MVPA), and sedentary time with circulating LECT2 and FGF21. Data were combined from two previous experimental studies in healthy volunteers (n = 141, male = 60%, mean ± SD age = 37 ± 19 years, body mass index (BMI) = 26.1 ± 6.3 kg·m-2). Sedentary time and MVPA were measured via an ActiGraph GT3X + accelerometer, while magnetic resonance imaging quantified liver fat. CRF was assessed using incremental treadmill tests. Generalized-linear models examined the association of CRF, sedentary time, and MVPA with LECT2 and FGF21 while controlling for key demographic and anthropometric variables. Interaction terms explored the moderating influence of age, sex, BMI, and CRF. In the fully adjusted models, each SD increase in CRF was independently associated with a 24% (95% CI: -37% to -9%, P = 0.003) lower plasma LECT2 concentration and 53% lower FGF21 concentration (95% CI: -73% to -22%, P = 0.004). Each SD increase in MVPA was independently associated with 55% higher FGF21 (95% CI: 12% to 114%, P = 0.006), and this relationship was stronger in those with lower BMI and higher levels of CRF. These findings demonstrate that CRF and wider activity behaviours may independently modulate the circulating concentrations of hepatokines and thereby influence inter-organ cross-talk.

No Influence of the Fat Mass and Obesity-Associated Gene rs9939609 Single Nucleotide Polymorphism on Blood Lipids in Young Males.

The fat mass and obesity-associated gene (FTO) rs9939609 A-allele is linked to obesity and dyslipidemia, yet the independent influence of this polymorphism on blood lipids remains equivocal. We examined the influence of the FTO rs9939609 polymorphism on fasting and postprandial blood lipids in individuals homozygous for the risk A-allele or T-allele with similar anthropometric and demographic characteristics. 12 AA and 12 TT males consumed a standardized meal after fasting overnight. Blood samples were collected at baseline (-1.5 h), before the meal (0 h), and for five hours postprandially to measure lipid, glucose, and insulin concentrations. Time-averaged total area under the curve (TAUC) values (0-5 h) were calculated and compared between genotypes. Fasting triacylglycerol (TG), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, non-esterified fatty acid (NEFA), glucose, and insulin concentrations were similar between groups (p ≥ 0.293). TAUC for TG was similar in AAs and TTs (95% confidence interval (CI) -0.52 to 0.31 mmol/L/h; p = 0.606). Likewise, TAUC values were similar for NEFA (95% CI -0.04 to 0.03 mmol/L/h; p = 0.734), glucose (95% CI -0.41 to 0.44 mmol/L/h; p = 0.951), and insulin (95% CI -6.87 to 2.83 pmol/L/h; p = 0.395). Blood lipids are not influenced by the FTO rs9939609 polymorphism, suggesting the FTO-dyslipidemia link is mediated by adiposity and weight management is important in preventing FTO-related lipid variations.

Influence of Short-Term Hyperenergetic, High-Fat Feeding on Appetite, Appetite-Related Hormones, and Food Reward in Healthy Men.

Short-term overfeeding may provoke compensatory appetite responses to correct the energy surplus. However, the initial time-course of appetite, appetite-related hormone, and reward-related responses to hyperenergetic, high-fat diets (HE-HFD) are poorly characterised. Twelve young healthy men consumed a HE-HFD (+50% energy, 65% fat) or control diet (36% fat) for seven days in a randomised crossover design. Mean appetite perceptions were determined during an oral glucose tolerance test (OGTT) before and after each diet. Fasted appetite perceptions, appetite-related hormones, and reward parameters were measured pre-diet and after 1-, 3- and 7-days of each diet. The HE-HFD induced a pre-to-post diet suppression in mean appetite during the OGTT (all ratings p ≤ 0.058, effect size (d) ≥ 0.31), and reduced the preference for high-fat vs. low-fat foods (main effect diet p = 0.036, d = 0.32). Fasted leptin was higher in the HE-HFD than control diet (main effect diet p < 0.001, d = 0.30), whilst a diet-by-time interaction (p = 0.036) revealed fasted acylated ghrelin was reduced after 1-, 3- and 7-days of the HE-HFD (all p ≤ 0.040, d ≥ 0.50 vs. pre-diet). Appetite perceptions and total peptide YY in the fasted state exhibited similar temporal patterns between the diets (diet-by-time interaction p ≥ 0.077). Seven days of high-fat overfeeding provokes modest compensatory changes in subjective, hormonal, and reward-related appetite parameters.

Microparticle Responses to Aerobic Exercise and Meal Consumption in Healthy Men.

PURPOSE: Microparticles (MP) are shed extracellular vesicles that express the prothrombotic tissue factor (TF). Aerobic exercise may reduce MP count and TF expression. This study investigated the impact of acute running or rest followed by standardized meal consumption on MP phenotypes and TF expression. METHODS: Fifteen males (age, 22.9 ± 3.3 yr; body mass, 81.9 ± 11.4 kg; V˙O2max, 54.9 ± 6.5 mL·kg·min; mean ± SD) completed 1 h of running (70% V˙O2max) or rest at 9:00 AM and consumed a standardized meal (1170 kcal, 43% CHO, 17% PRO, 40% fat) at 10:45 AM. Venous blood samples were taken at 9:00 AM, 10:00 AM, and 11:30 AM. The MP concentration, diameter, phenotypes, and TF expression were assessed using nanoparticle tracking analysis and flow cytometry. RESULTS: Nanoparticle tracking analysis identified no changes in MP concentration or diameter in response to time or trial. Flow cytometry revealed total MP count increased from 9:00 AM to 10:00 AM (1.62 ± 2.28 to 1.74 ± 2.61 × 10 L, P = 0.016, effect size (η) = 0.105), but was unaffected by trial. TF platelet-derived MP % reduced from 9:00 AM to 10:00 AM (44.0% ± 21.2% to 21.5% ± 9.3%, P = 0.001, η = 0.582) after exercise only (control, 36.8% ± 18.2% to 34.9% ± 11.9%; P = 0.972). TF neutrophil-derived MP percentage reduced from 9:00 AM to 11:30 AM (42.3% ± 17.2% to 25.1% ± 14.9%; P = 0.048, η = 0.801) in the exercise trial only (control, 28.5% ± 15.7% to 32.2% ± 9.6%; P = 0.508). CONCLUSIONS: Running induced a significant reduction in %TF platelet and neutrophil MP, suggesting a transient reduction in cardiovascular risk via reduced TF-stimulated thrombosis. This requires further investigation over longer periods in cardiovascular disease populations.

Interindividual Responses of Appetite to Acute Exercise: A Replicated Crossover Study.

PURPOSE: Acute exercise transiently suppresses appetite, which coincides with alterations in appetite-regulatory hormone concentrations. Individual variability in these responses is suspected, but replicated trials are needed to quantify them robustly. We examined the reproducibility of appetite and appetite-regulatory hormone responses to acute exercise and quantified the individual differences in responses. METHODS: Fifteen healthy, recreationally active men completed two control (60-min resting) and two exercise (60-min fasted treadmill running at 70% peak oxygen uptake) conditions in randomized sequences. Perceived appetite and circulating concentrations of acylated ghrelin and total peptide YY (PYY) were measured immediately before and after the interventions. Interindividual differences were explored by correlating the two sets of response differences between exercise and control conditions. Within-participant covariate-adjusted linear mixed models were used to quantify participant-condition interactions. RESULTS: Compared with control, exercise suppressed mean acylated ghrelin concentrations and appetite perceptions (all ES = 0.62-1.47, P < 0.001) and elevated total PYY concentrations (ES = 1.49, P < 0.001). For all variables, the standard deviation of the change scores was substantially greater in the exercise versus control conditions. Moderate-to-large positive correlations were observed between the two sets of control-adjusted exercise responses for all variables (r = 0.54-0.82, P ≤ 0.036). After adjusting for baseline measurements, participant-condition interactions were present for all variables (P ≤ 0.053). CONCLUSIONS: Our replicated crossover study allowed, for the first time, the interaction between participant and acute exercise response in appetite parameters to be quantified. Even after adjustment for individual baseline measurements, participants demonstrated individual differences in perceived appetite and hormone responses to acute exercise bouts beyond any random within-subject variability over time.

Individual Variation in Hunger, Energy Intake, and Ghrelin Responses to Acute Exercise.

PURPOSE: This study aimed to characterize the immediate and extended effect of acute exercise on hunger, energy intake, and circulating acylated ghrelin concentrations using a large data set of homogenous experimental trials and to describe the variation in responses between individuals. METHODS: Data from 17 of our group's experimental crossover trials were aggregated yielding a total sample of 192 young, healthy males. In these studies, single bouts of moderate to high-intensity aerobic exercise (69% ± 5% V˙O2 peak; mean ± SD) were completed with detailed participant assessments occurring during and for several hours postexercise. Mean hunger ratings were determined during (n = 178) and after (n = 118) exercise from visual analog scales completed at 30-min intervals, whereas ad libitum energy intake was measured within the first hour after exercise (n = 60) and at multiple meals (n = 128) during the remainder of trials. Venous concentrations of acylated ghrelin were determined at strategic time points during (n = 118) and after (n = 89) exercise. RESULTS: At group level, exercise transiently suppressed hunger (P < 0.010, Cohen's d = 0.77) but did not affect energy intake. Acylated ghrelin was suppressed during exercise (P < 0.001, Cohen's d = 0.10) and remained significantly lower than control (no exercise) afterward (P < 0.024, Cohen's d = 0.61). Between participants, there were notable differences in responses; however, a large proportion of this spread lay within the boundaries of normal variation associated with biological and technical assessment error. CONCLUSION: In young men, acute exercise suppresses hunger and circulating acylated ghrelin concentrations with notable diversity between individuals. Care must be taken to distinguish true interindividual variation from random differences within normal limits.