Ketone monoester ingestion increases postexercise serum erythropoietin concentrations in healthy men.

Intravenous ketone body infusion can increase erythropoietin (EPO) concentrations, but responses to ketone monoester ingestion postexercise are currently unknown. The purpose of this study was to assess the effect of ketone monoester ingestion on postexercise erythropoietin (EPO) concentrations. Nine healthy men completed two trials in a randomized, crossover design (1-wk washout). During trials, participants performed 1 h of cycling (initially alternating between 50% and 90% of maximal aerobic capacity for 2 min each interval, and then 50% and 80%, and 50% and 70% when the higher intensity was unsustainable). Participants ingested 0.8 g·kg-1 sucrose with 0.4 g·kg-1 protein immediately after exercise, and at 1, 2, and 3 h postexercise. During the control trial (CONTROL), no further nutrition was provided, whereas on the ketone monoester trial (KETONE), participants also ingested 0.29 g·kg-1 of the ketone monoester (R)-3-hydroxybutyl (R)-3-hydroxybutyrate immediately postexercise and at 1 and 2 h postexercise. Blood was sampled immediately postexercise, every 15 min in the first hour and hourly thereafter for 4 h. Serum EPO concentrations increased to a greater extent in KETONE than in CONTROL (time × condition interaction: P = 0.046). Peak serum EPO concentrations were higher with KETONE (means ± SD: 9.0 ± 2.3 IU·L-1) compared with CONTROL (7.5 ± 1.5 IU·L-1, P < 0.01). Serum ß-hydroxybutyrate concentrations were also higher, and glucose concentrations lower, with KETONE versus CONTROL (both P < 0.01). In conclusion, ketone monoester ingestion increases postexercise erythropoietin concentrations, revealing a new avenue for orally ingestible ketone monoesters to potentially alter hemoglobin mass.NEW & NOTEWORTHY To our knowledge, this study was the first to assess the effects of ketone monoester ingestion on erythropoietin concentrations after exercise. We demonstrated that ingestion of a ketone monoester postexercise increased serum erythropoietin concentrations and reduced serum glucose concentrations in healthy men. These data reveal the possibility for ketone monoesters to alter hemoglobin mass.

Whey Protein-Enriched and Carbohydrate-Rich Breakfasts Attenuate Insulinemic Responses to an ad libitum Lunch Relative to Extended Morning Fasting: A Randomized Crossover Trial.

BACKGROUND: Typical breakfast foods are rich in carbohydrate, so they not only elevate blood glucose during the morning, but also elicit a second-meal effect that can attenuate blood glucose responses in the afternoon. OBJECTIVES: To determine whether a reduced-carbohydrate protein-enriched breakfast can elicit similar effects on glucose control later in the day but without hyperglycemia in the morning. METHODS: In a randomized crossover design, 12 healthy men and women (age 22 ± 2 y, BMI 24.1 ± 3.6 kg·m-2; Mean ± SD) completed 3 experimental conditions. In all conditions, participants consumed an ad libitum lunch at 1200 ± 1 h but differed in terms of whether they had fasted all morning (control) or had consumed a standardized porridge breakfast at 0900 ± 1 h (320 ± 50 kcal; prescribed relative to resting metabolic rate) that was either carbohydrate-rich (50 ± 10 g CHO) or protein-enriched (that is, isoenergetic substitution of carbohydrate for 15 g whey protein isolate). RESULTS: The protein-enriched breakfast reduced the morning glycemic response (iAUC 87 ± 36 mmol·L-1·180 min) relative to the carbohydrate-rich breakfast (119 ± 37 mmol·L-1·180 min; P = 0.03). Despite similar energy intake at lunch in all 3 conditions (protein-enriched 769 ± 278 kcal; carbohydrate-rich 753 ± 223 kcal; fasting 790 ± 227 kcal), postlunch insulinemic responses were markedly attenuated when breakfasts had been consumed that were either protein-enriched (18.0 ± 8.0 nmol·L-1·120 min; P = 0.05) or carbohydrate-rich (16.0 ± 7.7 nmol·L-1·120 min; P = 0.005), relative to when lunch was consumed in an overnight fasted state (26.9 ± 13.5 nmol·L-1·120 min). CONCLUSIONS: Breakfast consumption attenuates insulinemic responses to a subsequent meal, achieved with consumption of energy-matched breakfasts typically high in carbohydrates or enriched with whey protein isolate relative to extended morning fasting. TRIAL REGISTRATION NUMBER: NCT03866720 (clinicaltrials.gov).

Restricting sugar or carbohydrate intake does not impact physical activity level or energy intake over 24 h despite changes in substrate use: a randomised crossover study in healthy men and women.

PURPOSE: To determine the effects of dietary sugar or carbohydrate restriction on physical activity energy expenditure, energy intake, and physiological outcomes across 24 h. METHODS: In a randomized, open-label crossover design, twenty-five healthy men (n = 10) and women (n = 15) consumed three diets over a 24-h period: moderate carbohydrate and sugar content (MODSUG = 50% carbohydrate [20% sugars], 15% protein, 35% fat); low sugar content (LOWSUG = 50% carbohydrate [< 5% sugars], 15% protein, 35% fat); and low carbohydrate content (LOWCHO = 8% carbohydrate [< 5% sugars], 15% protein, 77% fat). Postprandial metabolic responses to a prescribed breakfast (20% EI) were monitored under laboratory conditions before an ad libitum test lunch, with subsequent diet and physical activity monitoring under free-living conditions until blood sample collection the following morning. RESULTS: The MODSUG, LOWSUG and LOWCHO diets resulted in similar mean [95%CI] rates of both physical activity energy expenditure (771 [624, 919] vs. 677 [565, 789] vs. 802 [614, 991] kcal·d-1; p = 0.29] and energy intake (2071 [1794, 2347] vs. 2195 [1918, 2473] vs. 2194 [1890, 2498] kcal·d-1; P = 0.34), respectively. The LOWCHO condition elicited the lowest glycaemic and insulinaemic responses to breakfast (P < 0.01) but the highest 24-h increase in LDL-cholesterol concentrations (P < 0.001), with no differences between the MODSUG and LOWSUG treatments. Leptin concentrations decreased over 24-h of consuming LOWCHO relative to LOWSUG (p < 0.01). CONCLUSION: When energy density is controlled for, restricting either sugar or total dietary carbohydrate does not modulate physical activity level or energy intake over a 24-h period (~ 19-h free-living) despite substantial metabolic changes. CLINICAL TRIALS REGISTRATION ID: NCT03509610, https://clinicaltrials.gov/show/NCT03509610.

Divergent immunometabolic changes in adipose tissue and skeletal muscle with ageing in healthy humans.

KEY POINTS: Ageing is associated with increased systemic inflammation and metabolic dysfunction that contributes to the development of age-associated diseases. The role of adipose tissue in immunometabolic alterations that take place with ageing is unknown in humans. We show, in healthy, active and lean older adults, that adipose tissue, but not skeletal muscle, displays considerable pro-inflammatory transcriptomic, cellular and secretory changes, as well as a reduction in insulin signalling proteins compared to younger adults. These findings indicate that adipose tissue undergoes substantial immunometabolic alterations with ageing, and that these changes are tissue-specific and more profound than those observed in skeletal muscle or in the circulation. These results identify adipose tissue as an important tissue in the biological ageing process in humans, which may exhibit signs of immunometabolic dysfunction prior to systemic manifestation. ABSTRACT: Ageing and obesity are both characterized by inflammation and a deterioration in metabolic health. It is now clear that adipose tissue plays a major role in inflammation and metabolic control in obesity, although little is known about the role of adipose tissue in human ageing. To understand how ageing impacts adipose tissue, we characterized subcutaneous adipose tissue and skeletal muscle samples from twelve younger (27 ± 4 years [Young]) and twelve older (66 ± 5 years [Old]) active/non-obese males. We performed a wide-range of whole-body and tissue measures, including RNA-sequencing and multicolour flow cytometry. We also measured a range of inflammatory and metabolic proteins in the circulation and their release by adipose tissue, ex vivo. Both adipose tissue and muscle had ∼2-fold more immune cells per gram of tissue with ageing. In adipose tissue, this immune cell infiltration was driven by increased memory/effector T-cells, whereas, in muscle, the accumulation was driven by memory/effector T-cells and macrophages. Transcriptomic analysis revealed that, with ageing, adipose tissue, but not muscle, was enriched for inflammatory transcripts/pathways related to acquired and innate immunity. Ageing also increased the adipose tissue pro-inflammatory secretory profile. Insulin signalling protein content was reduced in adipose tissue, but not muscle. Our findings indicate that adipose tissue undergoes substantial immunometabolic changes with ageing in humans, and that these changes are tissue-specific and more profound than those observed in the circulation and skeletal muscle.

Physiological responses to carbohydrate overfeeding.

PURPOSE OF REVIEW: To consider emerging research into the physiological effects of excessive dietary carbohydrate intake, with a particular focus on interactions with physical activity. RECENT FINDINGS: A single episode of massive carbohydrate overload initiates physiological responses to stimulate additional peptide hormone secretion by the gut and the conversion of carbohydrate into lipid by the intestine, liver and adipose tissue. These acute responses maintain glycaemic control both via increased oxidation of carbohydrate (rather than lipid) and via nonoxidative disposal of surplus carbohydrate into endogenous glycogen and lipid storage depots. Sustained carbohydrate overfeeding therefore results in a chronic accumulation of lipid in the liver, skeletal muscle and adipose tissue, which can impair insulin sensitivity and cardiometabolic health in general. Beyond any direct effect of such lipid deposition on body mass/composition, there is not yet clear evidence of physiologically meaningful metabolic or behavioural adaptations to carbohydrate overfeeding in terms of other components of energy balance. However, regular physical exercise can mitigate the negative health effects of carbohydrate overfeeding, independent of any effect on the net carbohydrate surplus. SUMMARY: Research in this area has advanced understanding regarding the mechanisms of weight gain and associated health outcomes within the modern context of an abundant supply of dietary carbohydrate.

Resting skeletal muscle PNPLA2 (ATGL) and CPT1B are associated with peak fat oxidation rates in men and women but do not explain observed sex differences.

NEW FINDINGS: What is the central question of this study? What is the relationship between proteins in skeletal muscle and adipose tissue determined at rest and at peak rates of fat oxidation in men and women? What is the main finding and its importance? The resting contents of proteins in skeletal muscle involved in triglyceride hydrolysis and mitochondrial lipid transport were more strongly associated with peak fat oxidation rates than proteins related to lipid transport or hydrolysis in adipose tissue. Although females displayed higher relative rates of fat oxidation than males, this was not explained by the proteins measured in this study, suggesting that other factors determine sex differences in fat metabolism. ABSTRACT: We explored key proteins involved in fat metabolism that might be associated with peak fat oxidation (PFO) and account for sexual dimorphism in fuel metabolism during exercise. Thirty-six healthy adults [15 women; 40 ± 11 years of age; peak oxygen consumption 42.5 ± 9.5 ml (kg body mass)-1  min-1 ; mean ± SD] completed two exercise tests to determine PFO via indirect calorimetry. Resting adipose tissue and/or skeletal muscle biopsies were obtained to determine the adipose tissue protein content of PLIN1, ABHD5 (CGI-58), LIPE (HSL), PNPLA2 (ATGL), ACSL1, CPT1B and oestrogen receptor α (ERα) and the skeletal muscle protein content of FABP 3 (FABPpm), PNPLA2 (ATGL), ACSL1, CTP1B and ESR1 (ERα). Moderate strength correlations were found between PFO [in milligrams per kilogram of fat-free mass (FFM) per minute] and the protein content of PNPLA2 (ATGL) [rs  = 0.41 (0.03-0.68), P < 0.05] and CPT1B [rs  = 0.45 (0.09-0.71), P < 0.05] in skeletal muscle. No other statistically significant bivariate correlations were found consistently. Females had a greater relative PFO than males [7.1 ± 1.9 vs. 4.5 ± 1.3 and 7.3 ± 1.7 vs. 4.8 ± 1.2 mg (kg FFM)-1  min-1 in the adipose tissue (n = 14) and skeletal muscle (n = 12) subgroups, respectively (P < 0.05)]. No statistically significant sex differences were found in the content of these proteins. The regulation of PFO might involve processes relating to intramyocellular triglyceride hydrolysis and mitochondrial fatty acid transport, and adipose tissue is likely to play a more minor role than muscle. Sex differences in fat metabolism are likely to be attributable to factors other than the resting content of proteins in skeletal muscle and adipose tissue relating to triglyceride hydrolysis and fatty acid transport.

Physiological responses to maximal eating in men.

This study investigated metabolic, endocrine, appetite and mood responses to a maximal eating occasion in fourteen men (mean: age 28 (sd 5) years, body mass 77·2 (sd 6·6) kg and BMI 24·2 (sd 2·2) kg/m2) who completed two trials in a randomised crossover design. On each occasion, participants ate a homogenous mixed-macronutrient meal (pizza). On one occasion, they ate until 'comfortably full' (ad libitum) and on the other, until they 'could not eat another bite' (maximal). Mean energy intake was double in the maximal (13 024 (95 % CI 10 964, 15 084) kJ; 3113 (95 % CI 2620, 3605) kcal) compared with the ad libitum trial (6627 (95 % CI 5708, 7547) kJ; 1584 (95 % CI 1364, 1804) kcal). Serum insulin incremental AUC (iAUC) increased approximately 1·5-fold in the maximal compared with ad libitum trial (mean: ad libitum 43·8 (95 % CI 28·3, 59·3) nmol/l × 240 min and maximal 67·7 (95 % CI 47·0, 88·5) nmol/l × 240 min, P < 0·01), but glucose iAUC did not differ between trials (ad libitum 94·3 (95 % CI 30·3, 158·2) mmol/l × 240 min and maximal 126·5 (95 % CI 76·9, 176·0) mmol/l × 240 min, P = 0·19). TAG iAUC was approximately 1·5-fold greater in the maximal v. ad libitum trial (ad libitum 98·6 (95 % CI 69·9, 127·2) mmol/l × 240 min and maximal 146·4 (95 % CI 88·6, 204·1) mmol/l × 240 min, P < 0·01). Total glucagon-like peptide-1, glucose-dependent insulinotropic peptide and peptide tyrosine-tyrosine iAUC were greater in the maximal compared with ad libitum trial (P < 0·05). Total ghrelin concentrations decreased to a similar extent, but AUC was slightly lower in the maximal v. ad libitum trial (P = 0·02). There were marked differences on appetite and mood between trials, most notably maximal eating caused a prolonged increase in lethargy. Healthy men have the capacity to eat twice the energy content required to achieve comfortable fullness at a single meal. Postprandial glycaemia is well regulated following initial overeating, with elevated postprandial insulinaemia probably contributing.

Glucose control upon waking is unaffected by hourly sleep fragmentation during the night, but is impaired by morning caffeinated coffee.

Morning coffee is a common remedy following disrupted sleep, yet each factor can independently impair glucose tolerance and insulin sensitivity in healthy adults. Remarkably, the combined effects of sleep fragmentation and coffee on glucose control upon waking per se have never been investigated. In a randomised crossover design, twenty-nine adults (mean age: 21 (sd 1) years, BMI: 24·4 (sd 3·3) kg/m2) underwent three oral glucose tolerance tests (OGTT). One following a habitual night of sleep (Control; in bed, lights-off trying to sleep approximately 23.00-07.00 hours), the others following a night of sleep fragmentation (as Control but waking hourly for 5 min), with and without morning coffee approximately 1 h after waking (approximately 300 mg caffeine as black coffee 30 min prior to OGTT). Individualised peak plasma glucose and insulin concentrations were unaffected by sleep quality but were higher following coffee consumption (mean (normalised CI) for Control, Fragmented and Fragmented + Coffee, respectively; glucose: 8·20 (normalised CI 7·93, 8·47) mmol/l v. 8·23 (normalised CI 7·96, 8·50) mmol/l v. 8·96 (normalised CI 8·70, 9·22) mmol/l; insulin: 265 (normalised CI 247, 283) pmol/l; and 235 (normalised CI 218, 253) pmol/l; and 310 (normalised CI 284, 337) pmol/l). Likewise, incremental AUC for plasma glucose was higher in the Fragmented + Coffee trial compared with Fragmented. Whilst sleep fragmentation did not alter glycaemic or insulinaemic responses to morning glucose ingestion, if a strong caffeinated coffee is consumed, then a reduction in glucose tolerance can be expected.

Lipidomics reveals diurnal lipid oscillations in human skeletal muscle persisting in cellular myotubes cultured in vitro.

Circadian clocks play an important role in lipid homeostasis, with impact on various metabolic diseases. Due to the central role of skeletal muscle in whole-body metabolism, we aimed at studying muscle lipid profiles in a temporal manner. Moreover, it has not been shown whether lipid oscillations in peripheral tissues are driven by diurnal cycles of rest-activity and food intake or are able to persist in vitro in a cell-autonomous manner. To address this, we investigated lipid profiles over 24 h in human skeletal muscle in vivo and in primary human myotubes cultured in vitro. Glycerolipids, glycerophospholipids, and sphingolipids exhibited diurnal oscillations, suggesting a widespread circadian impact on muscle lipid metabolism. Notably, peak levels of lipid accumulation were in phase coherence with core clock gene expression in vivo and in vitro. The percentage of oscillating lipid metabolites was comparable between muscle tissue and cultured myotubes, and temporal lipid profiles correlated with transcript profiles of genes implicated in their biosynthesis. Lipids enriched in the outer leaflet of the plasma membrane oscillated in a highly coordinated manner in vivo and in vitro. Lipid metabolite oscillations were strongly attenuated upon siRNA-mediated clock disruption in human primary myotubes. Taken together, our data suggest an essential role for endogenous cell-autonomous human skeletal muscle oscillators in regulating lipid metabolism independent of external synchronizers, such as physical activity or food intake.

Frequent Carbohydrate Ingestion Reduces Muscle Glycogen Depletion and Postpones Fatigue Relative to a Single Bolus.

The timing of carbohydrate ingestion and how this influences net muscle glycogen utilization and fatigue has only been investigated in prolonged cycling. Past findings may not translate to running because each exercise mode is distinct both in the metabolic response to carbohydrate ingestion and in the practicalities of carbohydrate ingestion. To this end, a randomized, cross-over design was employed to contrast ingestion of the same sucrose dose either at frequent intervals (15 × 5 g every 5 min) or at a late bolus (1 × 75 g after 75 min) during prolonged treadmill running to exhaustion in six well-trained runners (V˙O2max 61 ± 4 ml·kg-1·min-1). The muscle glycogen utilization rate was lower in every participant over the first 75 min of running (Δ 0.51 mmol·kg dm-1·min-1; 95% confidence interval [-0.02, 1.04] mmol·kg dm-1·min-1) and, subsequently, all were able to run for longer when carbohydrate had been ingested frequently from the start of exercise compared with when carbohydrate was ingested as a single bolus toward the end of exercise (105.6 ± 3.0 vs. 96.4 ± 5.0 min, respectively; Δ 9.3 min, 95% confidence interval [2.8, 15.8] min). A moderate positive correlation was apparent between the magnitude of glycogen sparing over the first 75 min and the improvement in running capacity (r = .58), with no significant difference in muscle glycogen concentrations at the point of exhaustion. This study indicates that failure to ingest carbohydrates from the outset of prolonged running increases reliance on limited endogenous muscle glycogen stores-the ergolytic effects of which cannot be rectified by subsequent carbohydrate ingestion late in exercise.

Skipping Breakfast Before Exercise Creates a More Negative 24-hour Energy Balance: A Randomized Controlled Trial in Healthy Physically Active Young Men.

BACKGROUND: At rest, omission of breakfast lowers daily energy intake, but also lowers energy expenditure, attenuating any effect on energy balance. The effect of breakfast omission on energy balance when exercise is prescribed is unclear. OBJECTIVES: The aim of this study was to assess the effect on 24-h energy balance of omitting compared with consuming breakfast prior to exercise. METHODS: Twelve healthy physically active young men (age 23 ± 3 y, body mass index 23.6 ± 2.0 kg/m2) completed 3 trials in a randomized order (separated by >1 week): a breakfast of oats and milk (431 kcal; 65 g carbohydrate, 11 g fat, 19 g protein) followed by rest (BR); breakfast before exercise (BE; 60 min cycling at 50 % peak power output); and overnight fasting before exercise (FE). The 24-h energy intake was calculated based on the food consumed for breakfast, followed by an ad libitum lunch, snacks, and dinner. Indirect calorimetry with heart-rate accelerometry was used to measure substrate utilization and 24-h energy expenditure. A [6,6-2H2]glucose infusion was used to investigate tissue-specific carbohydrate utilization. RESULTS: The 24-h energy balance was -400 kcal (normalized 95% CI: -230, -571 kcal) for the FE trial; this was significantly lower than both the BR trial (492 kcal; normalized 95% CI: 332, 652 kcal) and the BE trial (7 kcal; normalized 95% CI: -153, 177 kcal; both P < 0.01 compared with FE). Plasma glucose utilization in FE (mainly representing liver glucose utilization) was positively correlated with energy intake compensation at lunch (r = 0.62, P = 0.03), suggesting liver carbohydrate plays a role in postexercise energy-balance regulation. CONCLUSIONS: Neither exercise energy expenditure nor restricted energy intake via breakfast omission were completely compensated for postexercise. In healthy men, pre-exercise breakfast omission creates a more negative daily energy balance and could therefore be a useful strategy to induce a short-term energy deficit. This trial was registered at clinicaltrials.gov as NCT02258399.

Preexercise breakfast ingestion versus extended overnight fasting increases postprandial glucose flux after exercise in healthy men.

The aim of this study was to characterize postprandial glucose flux after exercise in the fed versus overnight fasted state and to investigate the potential underlying mechanisms. In a randomized order, twelve men underwent breakfast-rest [(BR) 3 h semirecumbent], breakfast-exercise [(BE) 2 h semirecumbent before 60 min of cycling (50% peak power output)], and overnight fasted exercise [(FE) as per BE omitting breakfast] trials. An oral glucose tolerance test (OGTT) was completed after exercise (after rest on BR). Dual stable isotope tracers ([U-13C] glucose ingestion and [6,6-2H2] glucose infusion) and muscle biopsies were combined to assess postprandial plasma glucose kinetics and intramuscular signaling, respectively. Plasma intestinal fatty acid binding (I-FABP) concentrations were determined as a marker of intestinal damage. Breakfast before exercise increased postexercise plasma glucose disposal rates during the OGTT, from 44 g/120 min in FE {35 to 53 g/120 min [mean (normalized 95% confidence interval)] to 73 g/120 min in BE [55 to 90 g/120 min; P = 0.01]}. This higher plasma glucose disposal rate was, however, offset by increased plasma glucose appearance rates (principally OGTT-derived), resulting in a glycemic response that did not differ between BE and FE ( P = 0.11). Plasma I-FABP concentrations during exercise were 264 pg/ml (196 to 332 pg/ml) lower in BE versus FE ( P = 0.01). Breakfast before exercise increases postexercise postprandial plasma glucose disposal, which is offset (primarily) by increased appearance rates of orally ingested glucose. Therefore, metabolic responses to fed-state exercise cannot be readily inferred from studies conducted in a fasted state.

Venous blood provides lower glucagon-like peptide-1 concentrations than arterialized blood in the postprandial but not the fasted state: Consequences of sampling methods.

NEW FINDINGS: What is the central question of this study? Glucagon-like peptide-1 (GLP-1) is an important obesity/diabetes target, with effects dependent on circulating GLP-1 concentrations. Peripheral tissues extract GLP-1; therefore, sampling venous versus arterialized blood might provide different GLP-1 concentrations. This study examined whether arterialization alters GLP-1 concentrations during fasting and feeding. What is the main finding and its importance? This study demonstrates that venous blood provides lower postprandial but not fasting GLP-1 concentrations versus arterialized blood. Therefore, when accurate assessment of postprandial peripheral availability of GLP-1 is required, blood sampling methods should be considered carefully, reported clearly, and arterialization is recommended. ABSTRACT: Glucagon-like peptide-1 (GLP-1) displays concentration-dependent effects on metabolism, appetite and angiogenesis; therefore, accurate determination of circulating GLP-1 concentrations is important. In this study, we compared GLP-1 concentrations in venous versus arterialized blood in both fasted and fed conditions. Venous and arterialized blood samples were obtained simultaneously from 10 young, healthy men before and 30, 60 and 120 min after ingestion of 75 g glucose. Plasma GLP-1 concentrations increased in response to glucose ingestion (time effect, P < 0.01) and to a lesser extent in venous versus arterialized plasma (time × arterialization interaction, P < 0.01). Accordingly, the plasma incremental area under the curve was lower in venous versus arterialized plasma (974 ± 88 versus 1214 ± 115 pmol l (120 min)-1 , respectively, P = 0.049). In the postprandial state, there was a positive relationship between arterialized GLP-1 concentrations and the venous-arterialized difference in GLP-1 concentrations (r2  = 0.51; P < 0.01). Both arterialized and venous peak GLP-1 concentrations showed positive relationships with peak arterialized insulin concentrations (both r2  > 0.6, P < 0.01). Venous sampling results in lower concentrations of GLP-1 in the postprandial but not the fasted state compared with arterialized blood. This absolute difference is biologically meaningful and is magnified when GLP-1 availability is high. Therefore, sampling from arterialized blood may provide a better chance of detecting small differences in postprandial GLP-1 availability with interventions. If absolute GLP-1 concentrations are of interest, the blood sampling method should be considered carefully and reported clearly.

Home-Based Exercise Enhances Health-Related Quality of Life in Persons With Spinal Cord Injury: A Randomized Controlled Trial.

OBJECTIVE: To assess the influence of a home-based exercise intervention on indices of health-related quality of life (HRQOL) in persons with spinal cord injury (SCI). DESIGN: This was a randomized controlled trial (HOMEX-SCI; ISRCTN57096451). After baseline laboratory testing and a week of free-living physical activity monitoring, eligible participants were randomly assigned (2:1 allocation ratio) to a home-based moderate-intensity upper-body exercise intervention group (INT, n=13), or a lifestyle maintenance control group (CON, n=8), for 6 weeks. SETTING: Home-based with short laboratory visits immediately before and after the intervention/control period. PARTICIPANTS: Inactive participants (N=21) with chronic (>1yr) SCI (injury level

Feeding influences adipose tissue responses to exercise in overweight men.

Feeding profoundly affects metabolic responses to exercise in various tissues, but the effect of feeding status on human adipose tissue responses to exercise has never been studied. Ten healthy overweight men aged 26 ± 5 yr (mean ± SD) with a waist circumference of 105 ± 10 cm walked at 60% of maximum oxygen uptake under either fasted or fed conditions in a randomized, counterbalanced design. Feeding comprised 648 ± 115 kcal 2 h before exercise. Blood samples were collected at regular intervals to examine changes in metabolic parameters and adipokine concentrations. Adipose tissue samples were obtained at baseline and 1 h after exercise to examine changes in adipose tissue mRNA expression and secretion of selected adipokines ex vivo. Adipose tissue mRNA expression of pyruvate dehydrogenase kinase isozyme 4 (PDK4), adipose triglyceride lipase, hormone-sensitive lipase (HSL), fatty acid translocase/CD36, glucose transporter type 4 (GLUT4), and insulin receptor substrate 2 (IRS2) in response to exercise were lower in fed compared with fasted conditions (all P ≤ 0.05). Postexercise adipose IRS2 protein was affected by feeding (P ≤ 0.05), but Akt2, AMPK, IRS1, GLUT4, PDK4, and HSL protein levels were not different. Feeding status did not impact serum and ex vivo adipose secretion of IL-6, leptin, or adiponectin in response to exercise. This is the first study to show that feeding before acute exercise affects postexercise adipose tissue gene expression, and we propose that feeding is likely to blunt long-term adipose tissue adaptation to regular exercise.

Prior exercise alters the difference between arterialised and venous glycaemia: implications for blood sampling procedures.

Oral glucose tolerance and insulin sensitivity are common measures, but are determined using various blood sampling methods, employed under many different experimental conditions. This study established whether measures of oral glucose tolerance and oral glucose-derived insulin sensitivity (insulin sensitivity indices; ISI) differ when calculated from venous v. arterialised blood. Critically, we also established whether any differences between sampling methods are consistent across distinct metabolic conditions (after rest v. after exercise). A total of ten healthy men completed two trials in a randomised order, each consisting of a 120-min oral glucose tolerance test (OGTT), either at rest or post-exercise. Blood was sampled simultaneously from a heated hand (arterialised) and an antecubital vein of the contralateral arm (venous). Under both conditions, glucose time-averaged AUC was greater from arterialised compared with venous plasma but importantly, this difference was larger after rest relative to after exercise (0·99 (sd 0·46) v. 0·56 (sd 0·24) mmol/l, respectively; P<0·01). OGTT-derived ISIMatsuda and ISICederholm were lower when calculated from arterialised relative to venous plasma and the arterialised-venous difference was greater after rest v. after exercise (ISIMatsuda: 1·97 (sd 0·81) v. 1·35 (sd 0·57) arbitrary units (au), respectively; ISICederholm : 14·76 (sd 7·83) v. 8·70 (sd 3·95) au, respectively; both P<0·01). Venous blood provides lower postprandial glucose concentrations and higher estimates of insulin sensitivity, compared with arterialised blood. Most importantly, these differences between blood sampling methods are not consistent after rest v. post-exercise, preventing standardised venous-to-arterialised corrections from being readily applied.

Effects of dietary inorganic nitrate on blood pressure during and post-exercise recovery: A systematic review and meta-analysis of randomized placebo-controlled trials.

OBJECTIVES: A systematic review with meta-analysis was completed to study the effects of dietary inorganic nitrate (NO3-) oral ingestion from vegetables and salts on blood pressure responses during and following exercise. BACKGROUND: NO3- is a hypotensive agent with the potential to reduce blood pressure peaks during exercise and amplify exercise-induced hypotensive effects. Several randomized and controlled trials have investigated the effects of NO3- on hemodynamic responses to physical exercise, however this still has yet to be studied systematically. METHODS: The searches were conducted on EMBASE, Medline, and SPORTSDiscus databases. The study included masked randomized controlled trials (RCTs) with participants ≥18 years old. The NO3-intervention group received at least 50 mg NO3-/day with similar sources amid NO3- and placebo conditions. Included studies reported systolic blood pressure (SBP) or diastolic blood pressure (DBP) values during or following exercise performance. RESULTS: 1903 studies were identified, and twenty-six achieved the inclusion criteria. NO3- daily dosages ranged from 90 to 800 mg/day. Throughout exercise, SBP had smaller increases in the NO3- group (-2.81 mmHg (95%CI: -5.20 to -0.41), p=0.02. DBP demonstrated lower values in the NO3- group (-2.41 mmHg (95%CI: -4.02 to -0.79), p=0.003. In the post-exercise group, the NO3- group presented lower SBP values (-3.53 mmHg (95%CI: -5.65 to 1.41), p=0.001, while no changes were identified in DBP values between NO3- and placebo groups (p=0.31). Subgroup meta-analysis revealed that SBP baseline values, exercise type, duration of NO3- ingestion, and its dosages mediated blood pressure responses during and following exercise. CONCLUSIONS: NO3- ingestion prior to exercise attenuated the increases in SBP and DBP during exercise, and increased the decline in SBP after exercise. These results are dependent on factors that moderate the blood pressure responses (e.g., health status, type of exercise, resting blood pressure values).

Characterising 24-h skeletal muscle gene expression alongside metabolic & endocrine responses under diurnal conditions.

CONTEXT: Skeletal muscle plays a central role in the storage, synthesis, and breakdown of nutrients, yet little research has explored temporal responses of this human tissue, especially with concurrent measures of systemic biomarkers of metabolism. OBJECTIVE: To characterise temporal profiles in skeletal muscle expression of genes involved in carbohydrate metabolism, lipid metabolism, circadian clocks, and autophagy and descriptively relate them to systemic metabolites and hormones during a controlled laboratory protocol. METHODS: Ten healthy adults (9M/1F, mean ± SD: age: 30 ± 10 y; BMI: 24.1 ± 2.7 kg·m-2) rested in the laboratory for 37 hours with all data collected during the final 24 hours of this period (i.e., 0800-0800 h). Participants ingested hourly isocaloric liquid meal replacements alongside appetite assessments during waking before a sleep opportunity from 2200-0700 h. Blood samples were collected hourly for endocrine and metabolite analyses, with muscle biopsies occurring every 4 h from 1200 h to 0800 h the following day to quantify gene expression. RESULTS: Plasma insulin displayed diurnal rhythmicity peaking at 1804 h. Expression of skeletal muscle genes involved in carbohydrate metabolism (Name - Acrophase; GLUT4 - 1440 h; PPARGC1A -1613 h; HK2 - 1824 h) and lipid metabolism (FABP3 - 1237 h; PDK4 - 0530 h; CPT1B - 1258 h) displayed 24 h rhythmicity that reflected the temporal rhythm of insulin. Equally, circulating glucose (0019 h), NEFA (0456 h), glycerol (0432 h), triglyceride (2314 h), urea (0046 h), CTX (0507 h) and cortisol concentrations (2250 h) also all displayed diurnal rhythmicity. CONCLUSION: Diurnal rhythms were present in human skeletal muscle gene expression as well systemic metabolites and hormones under controlled diurnal conditions. The temporal patterns of genes relating to carbohydrate and lipid metabolism alongside circulating insulin are consistent with diurnal rhythms being driven in part by the diurnal influence of cyclic feeding and fasting.

Exercise counteracts the effects of short-term overfeeding and reduced physical activity independent of energy imbalance in healthy young men.

Physical activity can affect many aspects of metabolism but it is unclear to what extent this relies on manipulation of energy balance. Twenty-six active men age 25 ± 7 years (mean ± SD) were randomly assigned either to consume 50% more energy than normal by over-consuming their habitual diet for 7 days whilst simultaneously restricting their physical activity below 4000 steps day(-1) to induce an energy surplus (SUR group; n = 14) or to the same regimen but with 45 min of daily treadmill running at 70% of maximum oxygen uptake (SUR+EX group; n = 12). Critically, the SUR+EX group received additional dietary energy intake to account for the energy expended by exercise, thus maintaining a matched energy surplus. At baseline and follow-up, fasted blood samples and abdominal subcutaneous adipose tissue biopsies were obtained and oral glucose tolerance tests conducted. Insulinaemic responses to a standard glucose load increased 2-fold from baseline to follow-up in the SUR group (17 ± 16 nmol (120 min) l(-1); P = 0.002) whereas there was no change in the SUR+EX group (1 ± 6 nmol (120 min) l(-1)). Seven of 17 genes within adipose tissue were differentially expressed in the SUR group; expression of SREBP-1c, FAS and GLUT4 was significantly up-regulated and expression of PDK4, IRS2, HSL and visfatin was significantly down-regulated (P ≤ 0.05). The pAMPK/AMPK protein ratio in adipose tissue was significantly down-regulated in the SUR group (P = 0.005). Vigorous-intensity exercise counteracted most of the effects of short-term overfeeding and under-activity at the whole-body level and in adipose tissue, even in the face of a standardised energy surplus.

Understanding the role of physical activity on the pathway from intra-articular knee injury to post-traumatic osteoarthritis disease in young people: a scoping review protocol.

INTRODUCTION: The prevalence of intra-articular knee injuries and reparative surgeries is increasing in many countries. Alarmingly, there is a risk of developing post-traumatic osteoarthritis (PTOA) after sustaining a serious intra-articular knee injury. Although physical inactivity is suggested as a risk factor contributing to the high prevalence of the condition, there is a paucity of research characterising the association between physical activity and joint health. Consequently, the primary aim of this review will be to identify and present available empirical evidence regarding the association between physical activity and joint degeneration after intra-articular knee injury and summarise the evidence using an adapted Grading of Recommendations Assessment, Development and Evaluations. The secondary aim will be to identify potential mechanistic pathways through which physical activity could influence PTOA pathogenesis. The tertiary aim will be to highlight gaps in current understanding of the association between physical activity and joint degeneration following joint injury. METHODS: A scoping review will be conducted using the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews checklist and best-practice recommendations. The review will be guided by the following research question: what is the role of physical activity in the trajectory from intra-articular knee injury to PTOA in young men and women? We will identify primary research studies and grey literature by searching the electronic databases Scopus, Embase: Elsevier, PubMed, Web of Science: all databases, and Google Scholar. Reviewing pairs will screen abstracts, full texts and will extract data. Data will be presented descriptively using charts, graphs, plots and tables. ETHICS AND DISSEMINATION: This research does not require ethical approval due to the data being published and publicly available. This review will be submitted for publication in a peer-reviewed sports medicine journal irrespective of discoveries and disseminated through scientific conference presentations and social media. TRIAL REGISTRATION NUMBER: https://osf.io/84pnh/.