Are There Interindividual Responses of Cardiovascular Disease Risk Markers to Acute Exercise? A Replicate Crossover Trial.

PURPOSE: Using a replicated crossover design, we quantified the response heterogeneity of postprandial cardiovascular disease risk marker responses to acute exercise. METHODS: Twenty men (mean (SD) age, 26 (6) yr; body mass index, 23.9 (2.4) kg·m -2 ) completed four 2-d conditions (two control, two exercise) in randomized orders. On days 1 and 2, participants rested and consumed two high-fat meals over 9 h. Participants ran for 60 min (61 (7)% of peak oxygen uptake) on day 1 (6.5 to 7.5 h) of both exercise conditions. Time-averaged total area under the curve (TAUC) for triacylglycerol, glucose, and insulin were calculated from 11 venous blood samples on day 2. Arterial stiffness and blood pressure responses were calculated from measurements at baseline on day 1 and at 2.5 h on day 2. Consistency of individual differences was explored by correlating the two replicates of control-adjusted exercise responses for each outcome. Within-participant covariate-adjusted linear mixed models quantified participant-by-condition interactions and individual response SDs. RESULTS: Acute exercise reduced mean TAUC-triacylglycerol (-0.27 mmol·L -1 ·h; Cohen's d = 0.29, P = 0.017) and TAUC-insulin (-25 pmol·L -1 ·h; Cohen's d = 0.35, P = 0.022) versus control, but led to negligible changes in TAUC-glucose and the vascular outcomes (Cohen's d ≤ 0.36, P ≥ 0.106). Small-to-moderate, but nonsignificant, correlations were observed between the two response replicates ( r = -0.42 to 0.15, P ≥ 0.066). We did not detect any individual response heterogeneity. All participant-by-condition interactions were P ≥ 0.137, and all individual response SDs were small with wide 95% confidence intervals overlapping zero. CONCLUSIONS: Large trial-to-trial within-subject variability inhibited detection of consistent interindividual variability in postprandial metabolic and vascular responses to acute exercise.

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.

Sedentary Time Is Independently Related to Adipose Tissue Insulin Resistance in Adults With or at Risk of Type 2 Diabetes.

INTRODUCTION: This cross-sectional study examined associations of device-measured sedentary time and moderate-to-vigorous physical activity (MVPA) with adipose tissue insulin resistance in people with or at high risk of type 2 diabetes (T2DM). METHOD: Data were combined from six previous experimental studies (within our group) involving patients with T2DM or primary risk factors (median (interquartile range) age, 66.2 (66.0-70.8) yr; body mass index (BMI), 31.1 (28.0-34.4) kg·m -2 ; 62% male; n = 179). Adipose tissue insulin resistance was calculated as the product of fasted circulating insulin and nonesterified fatty acids (ADIPO-IR), whereas sedentary time and MVPA were determined from wrist-worn accelerometery. Generalized linear models examined associations of sedentary time and MVPA with ADIPO-IR with interaction terms added to explore the moderating influence of ethnicity (White European vs South Asian), BMI, age, and sex. RESULTS: In finally adjusted models, sedentary time was positively associated with ADIPO-IR, with every 30 min of sedentary time associated with a 1.80-unit (95% confidence interval, 0.51-3.06; P = 0.006) higher ADIPO-IR. This relationship strengthened as BMI increased ( ß = 3.48 (95% confidence interval, 1.50-5.46), P = 0.005 in the upper BMI tertile (≥33.2 kg·m -2 )). MVPA was unrelated to ADIPO-IR. These results were consistent in sensitivity analyses that excluded participants taking statins and/or metformin ( n = 126) and when separated into the participants with T2DM ( n = 32) and those at high risk ( n = 147). CONCLUSIONS: Sedentary time is positively related to adipose tissue insulin sensitivity in people with or at high risk of T2DM. This relationship strengthens as BMI increases and may help explain established relationships between greater sedentary time, ectopic lipid, and hyperglycemia.

Evaluating the Stability of Cellulose Nanofiber Pickering Emulsions Using MRI and Relaxometry.

Magnetic resonance imaging (MRI) relaxometry and diffusion methods were used to highlight the instability mechanisms of oil-in-water Pickering emulsions stabilized by cellulose nanofibers (CNFs). Four different Pickering emulsions using different oils (n-dodecane and olive oil) and concentrations of CNFs (0.5 and 1.0 wt %) were systematically investigated over a period of one month after emulsification. The separation into a free oil, emulsion layer, and serum layer and the distribution of flocculated/coalesced oil droplets in several hundred micrometers were captured in MR images using fast low-angle shot (FLASH) and rapid acquisition with relaxation enhancement (RARE) sequences. The components of the Pickering emulsions (e.g., free oil, emulsion layer, oil droplets, and serum layer) were observable by different voxelwise relaxation times and apparent diffusion coefficients (ADCs) and reconstructing in the apparent T1, T2, and ADC maps. The mean T1, T2, and ADC of the free oil and serum layer corresponded well with MRI results for pure oils and water, respectively. Comparing the relaxation properties and translational diffusion coefficients of pure dodecane and olive oil obtained from NMR and MRI resulted in similar T1 and ADC but significantly different T2 depending on the sequence used. The diffusion coefficients of olive oil measured by NMR were much slower than dodecane. The ADC of the emulsion layer for dodecane emulsions did not correlate with the viscosity of the emulsions as the CNF concentration increased, suggesting the effects of restricted diffusion of oil/water molecules due to droplet packing.

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.

The effect of acute and chronic exercise on hepatic lipid composition.

Exercise is recommended for those with, or at risk of nonalcoholic fatty liver disease (NAFLD), owing to beneficial effects on hepatic steatosis and cardiometabolic risk. Whilst exercise training reduces total intrahepatic lipid in people with NAFLD, accumulating evidence indicates that exercise may also modulate hepatic lipid composition. This metabolic influence is important as the profile of saturated (SFA), monounsaturated (MUFA), and polyunsaturated fatty acids (PUFA) dramatically affect the metabolic consequences of hepatic lipid accumulation; with SFA being especially lipotoxic. Relatedly, obesity and NAFLD are associated with hepatic PUFA depletion and elevated SFA. This review summarizes the acute (single bout) and chronic (exercise training) effects of exercise on hepatic lipid composition in rodents (acute studies: n = 3, chronic studies: n = 13) and humans (acute studies: n = 1, chronic studies: n = 3). An increased proportion of hepatic PUFA after acute and chronic exercise is the most consistent finding of this review. Mechanistically, this may relate to an enhanced uptake of adipose-derived PUFA (reflecting habitual diet), particularly in rodents. A relative decrease in the proportion of hepatic MUFA after chronic exercise is also documented repeatedly, particularly in rodent models with elevated hepatic MUFA. This outcome is related to decreased hepatic stearoyl-CoA desaturase-1 activity in some studies. Findings regarding hepatic SFA are less consistent and limited by the absence of metabolic challenge in rodent models. These findings require confirmation in well-controlled interventions in people with NAFLD. These studies will be facilitated by recently validated magnetic resonance spectroscopy techniques, able to precisely quantify hepatic lipid composition in vivo.

Physical activity is inversely associated with hepatic fibro-inflammation: A population-based cohort study using UK Biobank data.

Background & Aims: Physical activity (PA) is recommended in the management of non-alcoholic fatty liver disease (NAFLD) given its beneficial effects on liver fat and cardiometabolic risk. Using data from the UK Biobank population-cohort, this study examined associations between habitual PA and hepatic fibro-inflammation. Methods: A total of 840 men and women aged 55-70 years were included in this cross-sectional study. Hepatic fibro-inflammation (iron-corrected T1 [cT1]) and liver fat were measured using MRI, whilst body fat was measured using dual-energy X-ray absorptiometry. PA was measured using accelerometry. Generalised linear models examined associations between PA (light [LPA], moderate [MPA], vigorous [VPA], moderate-to-vigorous [MVPA] and mean acceleration) and hepatic cT1. Models were fitted for the whole sample and separately for upper and lower median groups for body and liver fat. Models were adjusted for sociodemographic and lifestyle variables. Results: In the full sample, LPA (-0.08 ms [-0.12 to -0.03]), MPA, (-0.13 ms [-0.21 to -0.05]), VPA (-1.16 ms [-1.81 to -0.51]), MVPA (-0.14 ms [-0.21 to -0.06]) and mean acceleration (-0.67 ms [-1.05 to-0.28]) were inversely associated with hepatic cT1. With the sample split by median liver or body fat, only VPA was inversely associated with hepatic cT1 in the upper median groups for body (-2.68 ms [-4.24 to -1.13]) and liver fat (-2.33 [-3.73 to -0.93]). PA was unrelated to hepatic cT1 in the lower median groups. Conclusions: Within a population-based cohort, device-measured PA is inversely associated with hepatic fibro-inflammation. This relationship is strongest with VPA and is greater in people with higher levels of body and liver fat. Lay summary: This study has shown that people who regularly perform greater amounts of physical activity have a reduced level of inflammation and fibrosis in their liver. This beneficial relationship is particularly strong when more intense physical activity is undertaken (i.e., vigorous-intensity), and is most visible in individuals with higher levels of liver fat and body fat.

A volumetric and intra-diffusion study of solutions of AlCl3 in two ionic liquids - [C2TMEDA][Tf2N] and [C4mpyr][Tf2N].

Intra-diffusion coefficients (DSi) have been measured for the ionic liquid constituent ions and aluminium-containing species in aluminium chloride (AlCl3) solutions in the ionic liquids 1-(2-dimethyl-aminoethyl)-dimethylethylammonium bis(trifluoromethylsulfonyl)amide ([C2TMEDA][Tf2N]) and N-butyl-N-methylpyrrolidinium bis(trifluoromethylsulfonyl)amide ([C4mpyr][Tf2N]), to investigate whether spectroscopically detected interactions between the ions and AlCl3 affect these properties. Such electrolyte solutions are of interest for the electrowinning of aluminium. The temperature, composition and molar volume dependences are investigated. Apparent (Vϕ,1) and partial molar (V1) volumes for AlCl3 have been calculated from solution densities. For [C2TMEDA][Tf2N] solutions, Vϕ,1 increases with increasing solute concentration; for [C4mpyr][Tf2N] solutions, it decreases. In pure [C2TMEDA][Tf2N], the cation diffuses more quickly than the anion, but this changes as the AlCl3 concentration increases. In the [C4mpyr][Tf2N] solutions, the intra-diffusion coefficient ratio remains equal to that for the pure ionic liquid and the aluminium species diffuses at approximately the same rate as the anion at each composition. The intra-diffusion coefficients can be fitted to the Ertl-Dullien free volume power law by superposing the iso-concentration curves with concentration dependent, but temperature independent, molar volume offsets. This suggests that they are primarily dependent on the molar volume and secondarily on a colligative thermodynamic factor due to dilution by AlCl3. AlCl3 complexation by [Tf2N]- and [C2TMEDA]+, confirmed by 27Al, 15N and 19F NMR spectroscopy, seems to play a minor role. Our results indicate that the application of free volume theories might be fruitful in the study of the transport properties of ionic liquid solutions and mixtures.

The effects of empagliflozin, dietary energy restriction, or both on appetite-regulatory gut peptides in individuals with type 2 diabetes and overweight or obesity: The SEESAW randomized, double-blind, placebo-controlled trial.

AIM: To assess the impact of the sodium-glucose co-transporter-2 (SGLT2) inhibitor empagliflozin (25 mg once-daily), dietary energy restriction, or both combined, on circulating appetite-regulatory peptides in people with type 2 diabetes (T2D) and overweight or obesity. MATERIALS AND METHODS: In a double-blind, placebo-controlled trial, 68 adults (aged 30-75 years) with T2D (drug naïve or on metformin monotherapy; HbA1c 6.0%-10.0% [42-86 mmol/mol]) and body mass index of 25 kg/m2 or higher were randomized to (a) placebo only, (b) placebo plus diet, (c) empagliflozin only or (d) empagliflozin plus diet for 24 weeks. Dietary energy restriction matched the estimated energy deficit elicited by SGLT2 inhibitor therapy through urinary glucose excretion (~360 kcal/day). The primary outcome was change in postprandial circulating total peptide-YY (PYY) during a 3-hour mixed-meal tolerance test from baseline to 24 weeks. Postprandial total glucagon-like peptide-1 (GLP-1), acylated ghrelin and subjective appetite perceptions formed secondary outcomes, along with other key components of energy balance. RESULTS: The mean weight loss in each group at 24 weeks was 0.44, 1.91, 2.22 and 5.74 kg, respectively. The change from baseline to 24 weeks in postprandial total PYY was similar between experimental groups and placebo only (mean difference [95% CI]: -8.6 [-28.6 to 11.4], 13.4 [-6.1 to 33.0] and 1.0 [-18.0 to 19.9] pg/ml in placebo-plus diet, empagliflozin-only and empagliflozin-plus-diet groups, respectively [all P ≥ .18]). Similarly, there was no consistent pattern of difference between groups for postprandial total GLP-1, acylated ghrelin and subjective appetite perceptions. CONCLUSIONS: In people with T2D and overweight or obesity, changes in postprandial appetite-regulatory gut peptides may not underpin the less than predicted weight loss observed with empagliflozin therapy. CLINICAL TRIALS REGISTRATION: NCT02798744, www. CLINICALTRIALS: gov; 2015-001594-40, www.EudraCT.ema.europa.eu; ISRCTN82062639, www.ISRCTN.org.

The effect of exercise training on adipose tissue insulin sensitivity: A systematic review and meta-analysis.

This systematic review and meta-analysis determined the impact of exercise training on adipose tissue insulin sensitivity in adults. Its scope extended to studies measuring whole-body and localized subcutaneous adipose tissue insulin sensitivity using validated techniques. Consensus from four studies demonstrates that exercise training improved whole-body adipose tissue insulin sensitivity when measured via stable-isotope lipid tracers (rate of appearance suppression in response to hyperinsulinemia). Meta-analysis of 20 studies (26 intervention arms) employing the adipose tissue insulin resistance index (ADIPO-IR) supported these findings (-10.63 [-14.12 to -7.15] pmol·L-1 × mmol·L-1 ). With ADIPO-IR, this response was greater in studies documenting weight loss and shorter sampling time (≤48 h) post-training. Overall, exercise training did not affect whole-body adipose tissue insulin sensitivity in seven studies (11 intervention arms) measuring the suppression of circulating non-esterified fatty acids in response to insulin infusion (1.51 [-0.12 to 3.14]%); however, subgroup analysis identified an enhanced suppression post-training in trials reporting weight loss. From four microdialysis studies, consensus indicates no effect of exercise training on localized (abdominal/femoral) adipose tissue insulin sensitivity, potentially suggesting that enhanced whole-body responses are related to improvements in central adipose depots. However, heterogeneity within microdialysis protocols dictates that findings must be viewed with caution.

One week of high-fat overfeeding alters bone metabolism in healthy males: A pilot study.

OBJECTIVES: Short periods of excessive consumption of indulgent high-fat foods are common in Western society, but the effect this has on bone is unknown. The aim of this pilot study was to explore how a 7-d hyperenergetic, high-fat diet affects candidate biomarkers of bone metabolism. METHODS: The study included 12 healthy men with a mean age of 24 y (SD = 4 y) and body mass index (BMI) of 24.1 kg/m2 (SD = 1.5). The men consumed a 7-d hyperenergetic, high-fat diet (HE-HFD; 20.9 [SD = 0.8] MJ; 65% total energy as fat) and a control (CON) diet (10.9 [SD = 2] MJ; 36% total energy as fat), in randomized, crossover order, with each trial separated by 3 wk. Markers of bone formation (P1NP) and bone resorption (CTx) were measured at baseline and after 1, 3, and 7 d of each diet. Bone metabolic responses were analyzed using two-factor repeated-measures analysis of variance and subsequent pairwise comparisons. RESULTS: There was a main effect of time (P < 0.05), but no trial (P = 0.270) or time- × -trial interaction (P = 0.693) effects for plasma concentrations of CTx. Mean CTx concentrations did not differ between trials (CON: 0.97 ng/mL [SD = 0.39]; HE-HFD: 1.03 ng/mL [SD = 0.22]; P = 0.225). There was a main effect of trial (P < 0.01), but no time (P = 0.138) or trial- × -interaction (P = 0.179) effects for plasma concentrations of P1NP. Mean P1NP concentrations were lower during the HE-HFD (61.79 ng/mL [SD = 26.54]) than during the CON diet (77.89 ng/mL [SD = 28.71]; P < 0.01). CONCLUSIONS: A 7-d hyperenergetic, high-fat diet reduces a marker of bone formation but does not affect a marker of bone resorption. This pilot study suggested that short periods of excessive energy and fat consumption may detrimentally affect bone health.

The role of hepatic lipid composition in obesity-related metabolic disease.

Obesity is a primary antecedent to non-alcoholic fatty liver disease whose cardinal feature is excessive hepatic lipid accumulation. Although total hepatic lipid content closely associates with hepatic and systemic metabolic dysfunction, accumulating evidence suggests that the composition of hepatic lipids may be more discriminatory. This review summarises cross-sectional human studies using liver biopsy/lipidomics and proton magnetic resonance spectroscopy to characterise hepatic lipid composition in people with obesity and related metabolic disease. A comprehensive literature search identified 26 relevant studies published up to 31st March 2021 which were included in the review. The available evidence provides a consistent picture showing that people with hepatic steatosis possess elevated saturated and/or monounsaturated hepatic lipids and a reduced proportion of polyunsaturated hepatic lipids. This altered hepatic lipid profile associates more directly with metabolic derangements, such as insulin resistance, and may be exacerbated in non-alcoholic steatohepatitis. Further evidence from lipidomic studies suggests that these deleterious changes may be related to defects in lipid desaturation and elongation, and an augmentation of the de novo lipogenic pathway. These observations are consistent with mechanistic studies implicating saturated fatty acids and associated bioactive lipid intermediates (ceramides, lysophosphatidylcholines and diacylglycerol) in the development of hepatic lipotoxicity and wider metabolic dysfunction, whilst monounsaturated fatty acids and polyunsaturated fatty acids may exhibit a protective role. Future studies are needed to prospectively determine the relevance of hepatic lipid composition for hepatic and non-hepatic morbidity and mortality; and to further evaluate the impact of therapeutic interventions such as pharmacotherapy and lifestyle interventions.

Accentuated early postprandial satiety in people with spinal cord injury versus able-bodied controls.

In persons with spinal cord injury (SCI), reduced fat-free mass and movement-related energy expenditure increase obesity risk. Although plausible mechanisms exist, it remains unknown whether impaired appetite regulation potentiates obesity risk in SCI. This study compared postprandial responses of appetite-related hormones, appetite perceptions and the sensitivity of appetite to covert preload energy manipulation in persons with SCI and able-bodied (AB) controls. In a counterbalanced order, 12 men with high-level SCI (≥T6 vertebrae) and 12 AB controls completed two trials, consuming covert high-energy (HE; 2513 kJ) and low-energy (LE; 1008 kJ) preloads on separate occasions. Subjective appetite perceptions were assessed at 30 min intervals following preload consumption (up to 150 min) and energy intake was determined from ad libitum test meals. Appetite-related hormone (total PYY, GLP-1 and acylated ghrelin) responses were measured in the HE trial only. Within the early postprandial phase (0-60 min), subjective ratings of fullness (d = 0.83) and satisfaction (d = 0.87) were higher (P ≤ 0.028) in the group with SCI. No group differences in PYY, GLP-1 or acylated ghrelin were detected in a fasted state or postprandially (d ≤ 0.64; p ≥ 0.053). Ad libitum energy intake was lower in the SCI group (1086 vs. 1713 kJ, respectively, d = 1.00; P = 0.020) but no effect of trial (preload) was found. These findings suggest that, following isocaloric preloads, postprandial satiety may be augmented, rather than attenuated, in people with SCI.

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.

An acute bout of swimming increases post-exercise energy intake in young healthy men and women.

Single bouts of land-based exercise (for example, walking, running, cycling) do not typically alter post-exercise energy intake on the day of exercise. However, anecdotal and preliminary empirical evidence suggests that swimming may increase appetite and energy intake. This study compared the acute effects of swimming on appetite, energy intake, and food preference and reward, versus exertion-matched cycling and a resting control. Thirty-two men (n = 17; mean ± SD age 24 ± 2 years, body mass index [BMI] 25.0 ± 2.6 kg/m2) and women (n = 15; age 22 ± 3 years, BMI 22.8 ± 2.3 kg/m2) completed three experimental trials (swimming, cycling, control) in a randomised, crossover design. The exercise trials involved 60-min of 'hard' exercise (self-selected rating of perceived exertion: 15) performed 90-min after a standardised breakfast. Food preference and reward were assessed via the Leeds Food Preference Questionnaire 15-min after exercise, whilst ad libitum energy intake was determined 30-min after exercise. The control trial involved identical procedures except no exercise was performed. Compared with control (3259 ± 1265 kJ), swimming increased ad libitum energy intake (3857 ± 1611 kJ; ES = 0.47, 95% CI of the mean difference between trials 185, 1010 kJ, P = 0.005); the magnitude of increase was smaller after cycling (3652 ± 1619 kJ; ES = 0.31, 95% CI -21, 805 kJ, P = 0.062). Ad libitum energy intake was similar between swimming and cycling (ES = 0.16, 95% CI -207, 618 kJ, P = 0.324). This effect was consistent across sexes and unrelated to food preference and reward which were similar after swimming and cycling compared with control. This study has identified an orexigenic effect of swimming. Further research is needed to identify the responsible mechanism(s), including the relevance of water immersion and water temperature per se.

Acute Hyperenergetic, High-Fat Feeding Increases Circulating FGF21, LECT2, and Fetuin-A in Healthy Men.

BACKGROUND: Hepatokines such as fibroblast growth factor 21 (FGF21), leukocyte cell-derived chemotaxin 2 (LECT2), fetuin-A, fetuin-B, and selenoprotein P (SeP) are liver-derived proteins that are modulated by chronic energy status and metabolic disease. Emerging data from rodent and cell models indicate that hepatokines may be sensitive to acute nutritional manipulation; however, data in humans are lacking. OBJECTIVE: The aim was to investigate the influence of hyperenergetic, high-fat feeding on circulating hepatokine concentrations, including the time course of responses. METHODS: In a randomized, crossover design, 12 healthy men [mean ± SD: age, 24 ± 4 y; BMI (kg/m2), 24.1 ± 1.5] consumed a 7-d hyperenergetic, high-fat diet [HE-HFD; +50% energy, 65% total energy as fat (32% saturated, 26% monounsaturated, 8% polyunsaturated)] and control diet (36% total energy as fat), separated by 3 wk. Whole-body insulin sensitivity was assessed before and after each diet using oral-glucose-tolerance tests. Fasting plasma concentrations of FGF21 (primary outcome), LECT2, fetuin-A, fetuin-B, SeP, and related metabolites were measured after 1, 3, and 7 d of each diet. Hepatokine responses were analyzed using 2-factor repeated-measures ANOVA and subsequent pairwise comparisons. RESULTS: Compared with the control, the HE-HFD increased circulating FGF21 at 1 d (105%) and 3 d (121%; P ≤ 0.040), LECT2 at 3 d (17%) and 7 d (32%; P ≤ 0.004), and fetuin-A at 7 d (7%; P = 0.028). Plasma fetuin-B and SeP did not respond to the HE-HFD. Whole-body insulin sensitivity was reduced after the HE-HFD by 31% (P = 0.021). CONCLUSIONS: Acute high-fat overfeeding augments circulating concentrations of FGF21, LECT2, and fetuin-A in healthy men. Notably, the time course of response varies between proteins and is transient for FGF21. These findings provide further insight into the nutritional regulation of hepatokines in humans and their interaction with metabolic homeostasis. This study was registered at clinicaltrials.gov as NCT03369145.

Effect of exercise intensity on circulating hepatokine concentrations in healthy men.

Fibroblast growth factor 21 (FGF21), follistatin and leukocyte cell-derived chemotaxin 2 (LECT2) are novel hepatokines that are modulated by metabolic stresses. This study investigated whether exercise intensity modulates the hepatokine response to acute exercise. Ten young, healthy men undertook three 8-h experimental trials: moderate-intensity exercise (MOD; 55% peak oxygen uptake), high-intensity exercise (HIGH; 75% peak oxygen uptake), and control (CON; rest), in a randomised, counterbalanced order. Exercise trials commenced with a treadmill run of varied duration to match gross exercise energy expenditure between trials (MOD vs HIGH; 2475 ± 70 vs 2488 ± 58 kJ). Circulating FGF21, follistatin, LECT2, glucagon, insulin, glucose and nonesterified fatty acids (NEFA) were measured before exercise and at 0, 1, 2, 4, and 7 h postexercise. Plasma FGF21 concentrations were increased up to 4 h postexercise compared with CON (P ≤ 0.022) with greater increases observed at 1, 2, and 4 h postexercise during HIGH versus MOD (P ≤ 0.025). Irrespective of intensity (P ≥ 0.606), plasma follistatin concentrations were elevated at 4 and 7 h postexercise (P ≤ 0.053). Plasma LECT2 concentrations were increased immediately postexercise (P ≤ 0.046) but were not significant after correcting for plasma volume shifts. Plasma glucagon (1 h; P = 0.032) and NEFA (4 and 7 h; P ≤ 0.029) responses to exercise were accentuated in HIGH versus MOD. These findings demonstrate that acute exercise augments circulating FGF21 and follistatin. Exercise-induced changes in FGF21 are intensity-dependent and may support the greater metabolic benefit of high-intensity exercise.

A Simple and Effective Binomial Block Based Pulse Sequence Capable of Suppressing Multiple NMR Signals.

A binomial-like block based multiple suppression NMR pulse sequence, termed MULTI-GATE-FSB, that is simple to implement with outstanding suppression performance for multiple solvent signals (or multiple resonances) is investigated. The sequence was tested on two water-alcohol solvent systems, and a standard lysozyme sample, with suppression of three or four regions (though it is extendable to any number of regions). The suppression of all solvent signals was possible in the alcohol-water systems tested with both long and short recycle delays and without the requirement for lengthy presaturation pulses. Such a sequence holds promise not only for LC-NMR applications and solvent suppression but for multiple suppression applications in general (e.g., analysis of impurities/components).

NMR diffusion and relaxation studies of 2-nitroimidazole and albumin interactions.

Nitroimidazole derivatives are of current interest in the development of hypoxia targeting agents and show potential in the establishment of quantitative measures of tumor hypoxia. In this study, the binding of 2-nitroimidazole to albumin was probed using NMR diffusion and relaxation measurements. Binding studies were conducted at three different protein concentrations (0.23, 0.30 and 0.38mM) with drug concentrations ranging from 0.005-0.16M at 298K. Quantitative assessments of the binding model were made by evaluating the number of binding sites, n, and association constant, K. These were determined to be 21±3 and 53±4M-1, respectively.

Physical characterization using diffusion NMR spectroscopy.

NMR diffusion measurements (or dNMR) provide a powerful tool for analysis of solution organization and microgeometry of the environment by probing random molecular motion. Being a very versatile method, dNMR can be applied to a large variety of samples and systems. Here, a brief introduction into dNMR and a summary of recent advances in the field are presented. The research topics include restricted diffusion, anisotropic diffusion, polymer dynamics, solution structuring and dNMR method development. The dNMR studied systems include plants, cells (cell models), liquid crystals, polymer solutions, ionic liquids, supercooled solutions, untreated water, amino acid solutions and more. It is demonstrated how a variety of dNMR methods can be applied to a system to extract the data on particular structures present among, formed by or surrounding the diffusing particles. It is also demonstrated how dNMR methods can be developed to allow probing larger geometries, low sample concentrations and faster processes. Copyright © 2016 John Wiley & Sons, Ltd.