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PURPOSE: 1) To investigate the effect of caffeine on exogenous carbohydrate (CHO) oxidation and glucose kinetics during exercise; and 2) to determine whether combined ingestion of caffeine and CHO enhanced cycling performance compared with CHO alone. METHODS:: Ten endurance-trained cyclists performed three experimental trials consisting of 105 min steady-state (SS) cycling at 62% VO2max followed by a time trial (TT) lasting approximately 45 min. During exercise, subjects ingested either of the following: a 6.4% glucose solution (GLU), a 6.4% glucose plus caffeine solution providing 5.3 mg.kg of caffeine (GLU + CAF), or a placebo (PLA). Glucose solutions contained a trace amount of [U-C]glucose, and eight subjects received a primed continuous [6,6-H2]glucose infusion. RESULTS:: Peak exogenous CHO oxidation rates were not significantly different between GLU and GLU + CAF trials (52.6 +/- 2.7 and 49.1 +/- 2.1 mumol.kg.min, respectively). Rates of appearance (Ra) and disappearance (Rd) of glucose were significantly higher with CHO ingestion than PLA (P < 0.01) but were not significantly different between GLU and GLU + CAF trials. Performance times were 43.45 +/- 0.86, 45.45 +/- 1.07, and 47.40 +/- 1.30 min for GLU + CAF, GLU, and PLA, respectively. Therefore, GLU + CAF ingestion enhanced TT performance by 4.6% (P < 0.05) compared with GLU and 9% (P < 0.05) compared with PLA. CONCLUSION:: The coingestion of caffeine (5.3 mg.kg) with CHO during exercise enhanced TT performance by 4.6% compared with CHO and 9.0% compared with water placebo. However, caffeine did not influence exogenous CHO oxidation or glucose kinetics during SS exercise. [ABSTRACT FROM AUTHOR]

The role of ghrelin metabolism in anorexia of ageing is unclear. The aim of this study was to determine acyl-ghrelin, total ghrelin, and ghrelin O-acyltransferase concentrations when fasted and in responses to feeding in older adults exhibiting anorexia of ageing. Twenty-five older adults (OA; 15f, 74 ± 7 years, 24.5 kg·m -2 ) and twelve younger adults (YA; 6f, 21 ± 2 years, 24.4 kg·m -2 ) provided a fasted measure of subjective appetite and fasted blood sample (0 min) before consuming a standardised porridge breakfast meal (450 kcal). Appetite was measured every 30 min for 240 min and blood was sampled at 30, 60, 90, 120, 180 and 240 min while participants rested. At 240 min, an ad libitum pasta-based lunch meal was consumed. Older adults were identified as those with healthy appetite (HA-OA) or low appetite (LA-OA), based on habitual energy intake, self-report appetite, BMI, and ad libitum lunch intake. YA ate more at lunch (1108 ± 235 kcal) than HA-OA (653 ± 133 kcal, p = 0.007) and LA-OA (369 ± 168 kcal; p < 0.001). LA-OA, but not HA-OA, had higher fasted concentrations of acyl- and total ghrelin than YA (acyl-ghrelin: 621 ± 307 pg·mL -1 vs. 353 ± 166 pg·mL -1 , p = 0.047; total ghrelin: 1333 ± 702 pg·mL -1 vs. 636 ± 251 pg·mL -1 , p = 0.006). Acyl-ghrelin (60 min and 90 min) and total ghrelin (90 min) were suppressed to a greater extent for LA-OA than for YA (p < 0.05). No differences were observed in subjective appetite, acyl-to-total ghrelin ratio, or plasma GOAT content (p > 0.1). Higher fasting ghrelin and an augmented ghrelin response to feeding in LA-OA, but not HA-OA, suggests that alterations to ghrelin metabolism are not functions of ageing per se and may be independent causal mechanisms of anorexia of ageing., Competing Interests: Declaration of competing interest This work was supported by a Wellcome Trust Institutional Strategic Support Fund award. The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: This study aimed to determine whether the pattern of carbohydrate sports drink ingestion during prolonged submaximal running affects exogenous carbohydrate oxidation rates and gastrointestinal (GI) comfort., Methods: Twelve well-trained male runners (27 ± 7 yr; 67.9 ± 6.7 kg; V˙O2peak, 68 ± 7 mL·kg·min) completed two exercise trials of 100 min steady-state running at 70%V˙O2peak. In each of the trials, 1 L of a 10% dextrose solution, enriched with [U-C] glucose, was consumed as either 200 mL every 20 min (CHO-20) or 50 mL every 5 min (CHO-5). Expired breath and venous blood samples were collected at rest and every 20 min during exercise. Subjective scales of GI comfort were recorded at regular intervals., Results: Average exogenous carbohydrate oxidation rates were 23% higher during exercise in CHO-20 (0.38 ± 0.11 vs 0.31 ± 0.11 g·min; P = 0.017). Peak exogenous carbohydrate oxidation was also higher in CHO-20 (0.68 ± 0.14 g·min vs 0.61 ± 0.14 g·min; P = 0.004). During exercise, total carbohydrate oxidation (CHO-20, 2.15 ± 0.47; CHO-5, 2.23 ± 0.45 g·min, P = 0.412) and endogenous carbohydrate oxidation (CHO-20, 1.78 ± 0.45; CHO-5, 1.92 ± 0.40 g·min; P = 0.148) were not different between trials. Average serum glucose (P = 0.952) and insulin (P = 0.373) concentrations were not different between trials. There were no differences in reported symptoms of GI comfort and stomach bloatedness (P > 0.05), with only 3% of reported scores classed as severe (≥5 out of 10)., Conclusion: Ingestion of a larger volume of carbohydrate solution at less frequent intervals during prolonged submaximal running increased exogenous carbohydrate oxidation rates. Neither drinking pattern resulted in increased markers of GI discomfort to a severe level.

Context: It is unclear how white adipose tissue (WAT) inflammatory signaling proteins respond during the early stages of overnutrition., Objective: To investigate the effect of short-term, high-fat overfeeding on fasting abdominal subcutaneous WAT total content and phosphorylation of proteins involved in nuclear factor-κB (NF-κB) inflammatory signaling, systemic metabolic and inflammatory biomarkers., Design: Individuals consumed a high-fat (65% total energy from total fat), high-energy (50% above estimated energy requirements) diet for 7 days., Results: Fifteen participants (aged 27 ± 1 years; body mass index 24.4 ± 0.6 kg/m2) completed the study. Body mass increased following high-fat overfeeding (+1.2 ± 0.2 kg; P < 0.0001). However, total content and phosphorylation of proteins involved in NF-κB inflammatory signaling were unchanged following the intervention. Fasting serum glucose (+0.2 ± 0.0 mmol/L), total cholesterol (+0.4 ± 0.1 mmol/L), low-density lipoprotein cholesterol (+0.3 ± 0.1 mmol/L), high-density lipoprotein cholesterol (+0.2 ± 0.0 mmol/L), and lipopolysaccharide-binding protein (LBP; +4.7 ± 2.1 µg/mL) increased, whereas triacylglycerol concentrations (-0.2 ± 0.1 mmol/L) decreased following overfeeding (all P < 0.05). Systemic biomarkers (insulin, soluble cluster of differentiation 14 [CD14], C-reactive protein, interleukin-6, tumor necrosis factor-α and monocyte chemoattractant protein-1) and the proportion and concentration of circulating CD14+ monocytes were unaffected by overfeeding., Conclusion: Acute lipid oversupply did not impact on total content or phosphorylation of proteins involved in WAT NF-κB inflammatory signaling, despite modest weight gain and metabolic alterations. Systemic LBP, which is implicated in the progression of low-grade inflammation during the development of obesity, increased in response to a 7-day high-fat overfeeding period., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Eight well-trained cyclists ingested 68 g·h -1 of a carbohydrate-electrolyte solution with sodium alginate and pectin (CHO-ALG) or a taste and carbohydrate type-matched carbohydrate-electrolyte solution (CHO) during 120 min of cycling at 55% maximal power followed by an ∼20 min time trial. Oxygen uptake, carbon dioxide production, blood glucose concentration, substrate oxidation, gastrointestinal symptoms, and time trial performance (CHO-ALG: 1219 ± 84 s, CHO: 1267 ± 102 s; P = 0.185) were not different between trials. Novelty Inclusion of sodium alginate and pectin in a carbohydrate drink does not influence blood glucose, substrate oxidation, gastrointestinal comfort, or performance in cyclists.

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., (Copyright © The Author(s) 2020.)

Given the common view that pre-exercise nutrition/breakfast is important for performance, the present study investigated whether breakfast influences resistance exercise performance via a physiological or psychological effect. Twenty-two resistance-trained, breakfast-consuming men completed three experimental trials, consuming water-only (WAT), or semi-solid breakfasts containing 0 g/kg (PLA) or 1·5 g/kg (CHO) maltodextrin. PLA and CHO meals contained xanthan gum and low-energy flavouring (approximately 122 kJ), and subjects were told both 'contained energy'. At 2 h post-meal, subjects completed four sets of back squat and bench press to failure at 90 % ten repetition maximum. Blood samples were taken pre-meal, 45 min and 105 min post-meal to measure serum/plasma glucose, insulin, ghrelin, glucagon-like peptide-1 and peptide tyrosine-tyrosine concentrations. Subjective hunger/fullness was also measured. Total back squat repetitions were greater in CHO (44 (sd 10) repetitions) and PLA (43 (sd 10) repetitions) than WAT (38 (sd 10) repetitions; P < 0·001). Total bench press repetitions were similar between trials (WAT 37 (sd 7) repetitions; CHO 39 (sd 7) repetitions; PLA 38 (sd 7) repetitions; P = 0·130). Performance was similar between CHO and PLA trials. Hunger was suppressed and fullness increased similarly in PLA and CHO, relative to WAT (P < 0·001). During CHO, plasma glucose was elevated at 45 min (P < 0·05), whilst serum insulin was elevated (P < 0·05) and plasma ghrelin suppressed at 45 and 105 min (P < 0·05). These results suggest that breakfast/pre-exercise nutrition enhances resistance exercise performance via a psychological effect, although a potential mediating role of hunger cannot be discounted.

Key Points: We have recently shown that a high-fat, high-calorie (HFHC) diet decreases whole body glucose clearance without impairing skeletal muscle insulin signalling, in healthy lean individuals. These diets are also known to increase skeletal muscle IMTG stores, but the effect on lipid metabolites leading to skeletal muscle insulin resistance has not been investigated. This study measured the effect of 7 days' HFHC diet on (1) skeletal muscle concentration of lipid metabolites, and (2) potential changes in the perilipin (PLIN) content of the lipid droplets storing intramuscular triglyceride (IMTG). The HFHC diet increased PLIN3 protein expression and redistributed PLIN2 to lipid droplet stores in type I fibres. The HFHC diet increased IMTG content in type I fibres, while lipid metabolite concentrations remained the same. The data suggest that the increases in IMTG stores assists in reducing the accumulation of lipid metabolites known to contribute to skeletal muscle insulin resistance., Abstract: A high-fat, high-calorie (HFHC) diet reduces whole body glucose clearance without impairing skeletal muscle insulin signalling in healthy lean individuals. HFHC diets also increase skeletal muscle lipid stores. However, unlike certain lipid metabolites, intramuscular triglyceride (IMTG) stored within lipid droplets (LDs) does not directly contribute to skeletal muscle insulin resistance. Increased expression of perilipin (PLIN) proteins and colocalisation to LDs has been shown to assist in IMTG storage. We aimed to test the hypothesis that 7 days on a HFHC diet increases IMTG content while minimising accumulation of lipid metabolites known to disrupt skeletal muscle insulin signalling in sedentary and obese individuals. We also aimed to identify changes in expression and subcellular distribution of proteins involved in IMTG storage. Muscle biopsies were obtained from the m. vastus lateralis of 13 (11 males, 2 females) healthy lean individuals (age: 23 ± 2.5 years; body mass index: 24.5 ± 2.4 kg m -2 ), following an overnight fast, before and after consuming a high-fat (64% energy), high-calorie (+47% kcal) diet for 7 days. After the HFHC diet, IMTG content increased in type I fibres only (+101%; P < 0.001), whereas there was no change in the concentration of either total diacylglycerol (P = 0.123) or total ceramides (P = 0.150). Of the PLINs investigated, only PLIN3 content increased (+50%; P < 0.01) solely in type I fibres. LDs labelled with PLIN2 increased (+80%; P < 0.01), also in type I fibres only. We propose that these adaptations of LDs support IMTG storage and minimise accumulation of lipid metabolites to protect skeletal muscle insulin signalling following 7 days' HFHC diet., (© 2020 The Authors. The Journal of Physiology © 2020 The Physiological Society.)

The global prevalence of obesity and obesity-associated cardiometabolic diseases is a significant public health burden. Chronic low-grade inflammation in metabolic tissues such as white adipose tissue (WAT) is linked to obesity and may play a role in disease progression. The overconsumption of dietary fat has been suggested to modulate the WAT inflammatory environment. It is also recognised that fats varying in degree of fatty acid saturation may elicit differential WAT inflammatory responses. This information has originated predominantly from animal or cell models and translation into human participants in vivo remains limited. This review will summarise human intervention studies investigating the effect of dietary fat quantity and quality on subcutaneous WAT inflammation, with a specific focus on the toll-like receptor 4 (TLR4)/NF-κB and nucleotide-binding and oligomerisation domain-like receptor, leucine-rich repeat and pyrin domain-containing 3 (NLRP3) inflammasome molecular signalling pathways. Overall, firm conclusions are hard to draw regarding the effect of dietary fat quantity and quality on WAT inflammatory responses due to the heterogeneity of study designs, diet composition and participant cohorts recruited. Previous studies have predominantly focused on measures of WAT gene expression. It is suggested that future work includes measures of WAT total content and phosphorylation of proteins involved in TLR4/NF-κB and NLRP3 signalling as this is more representative of alterations in WAT physiological function. Understanding pathways linking the intake of total fat and specific fatty acids with WAT metabolic-inflammatory responses may have important implications for public health by informing dietary guidelines aimed at cardiometabolic risk reduction.

Context: The mechanisms responsible for dietary fat-induced insulin resistance of skeletal muscle and its microvasculature are only partially understood., Objective: To determine the impact of high-fat overfeeding on postprandial glucose fluxes, muscle insulin signaling, and muscle microvascular endothelial nitric oxide synthase (eNOS) content and activation., Design: Fifteen non-obese volunteers consumed a high-fat (64%) high-energy (+47%) diet for 7 days. Experiments were performed before and after the diet. Stable isotope tracers were used to determine glucose fluxes in response to carbohydrate plus protein ingestion. Muscle insulin signaling was determined as well as the content and activation state of muscle microvascular eNOS., Results: High-fat overfeeding impaired postprandial glycemic control as demonstrated by higher concentrations of glucose (+11%; P = 0.004) and insulin (+19%; P = 0.035). Carbohydrate plus protein ingestion suppressed endogenous glucose production to a similar extent before and after the diet. Conversely, high-fat overfeeding reduced whole-body glucose clearance (-16%; P = 0.021) and peripheral insulin sensitivity (-26%; P = 0.006). This occurred despite only minor alterations in skeletal muscle insulin signaling. High-fat overfeeding reduced eNOS content in terminal arterioles (P = 0.017) and abolished the increase in eNOS Ser1177 phosphorylation that was seen after carbohydrate plus protein ingestion., Conclusion: High-fat overfeeding impaired whole-body glycemic control due to reduced glucose clearance, not elevated endogenous glucose production. The finding that high-fat overfeeding abolished insulin-mediated eNOS Ser1177 phosphorylation in the terminal arterioles suggests that impairments in the vasodilatory capacity of the skeletal muscle microvasculature may contribute to early dietary fat-induced impairments in glycemic control., (© Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

GDF15 is an established biomarker of cellular stress. The fact that it signals via a specific hindbrain receptor, GFRAL, and that mice lacking GDF15 manifest diet-induced obesity suggest that GDF15 may play a physiological role in energy balance. We performed experiments in humans, mice, and cells to determine if and how nutritional perturbations modify GDF15 expression. Circulating GDF15 levels manifest very modest changes in response to moderate caloric surpluses or deficits in mice or humans, differentiating it from classical intestinally derived satiety hormones and leptin. However, GDF15 levels do increase following sustained high-fat feeding or dietary amino acid imbalance in mice. We demonstrate that GDF15 expression is regulated by the integrated stress response and is induced in selected tissues in mice in these settings. Finally, we show that pharmacological GDF15 administration to mice can trigger conditioned taste aversion, suggesting that GDF15 may induce an aversive response to nutritional stress., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Post-exercise recovery is a multi-facetted process that will vary depending on the nature of the exercise, the time between exercise sessions and the goals of the exerciser. From a nutritional perspective, the main considerations are: (1) optimisation of muscle protein turnover; (2) glycogen resynthesis; (3) rehydration; (4) management of muscle soreness; (5) appropriate management of energy balance. Milk is approximately isotonic (osmolality of 280-290 mosmol/kg), and the mixture of high quality protein, carbohydrate, water and micronutrients (particularly sodium) make it uniquely suitable as a post-exercise recovery drink in many exercise scenarios. Research has shown that ingestion of milk post-exercise has the potential to beneficially impact both acute recovery and chronic training adaptation. Milk augments post-exercise muscle protein synthesis and rehydration, can contribute to post-exercise glycogen resynthesis, and attenuates post-exercise muscle soreness/function losses. For these aspects of recovery, milk is at least comparable and often out performs most commercially available recovery drinks, but is available at a fraction of the cost, making it a cheap and easy option to facilitate post-exercise recovery. Milk ingestion post-exercise has also been shown to attenuate subsequent energy intake and may lead to more favourable body composition changes with exercise training. This means that those exercising for weight management purposes might be able to beneficially influence post-exercise recovery, whilst maintaining the energy deficit created by exercise.

Intermittent energy restriction (IER) involves short periods of severe energy restriction interspersed with periods of adequate energy intake, and can induce weight loss. Insulin sensitivity is impaired by short-term, complete energy restriction, but the effects of IER are not well known. In randomised order, fourteen lean men (age: 25 (sd 4) years; BMI: 24 (sd 2) kg/m2; body fat: 17 (4) %) consumed 24-h diets providing 100 % (10 441 (sd 812) kJ; energy balance (EB)) or 25 % (2622 (sd 204) kJ; energy restriction (ER)) of estimated energy requirements, followed by an oral glucose tolerance test (OGTT; 75 g of glucose drink) after fasting overnight. Plasma/serum glucose, insulin, NEFA, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP) and fibroblast growth factor 21 (FGF21) were assessed before and after (0 h) each 24-h dietary intervention, and throughout the 2-h OGTT. Homoeostatic model assessment of insulin resistance (HOMA2-IR) assessed the fasted response and incremental AUC (iAUC) or total AUC (tAUC) were calculated during the OGTT. At 0 h, HOMA2-IR was 23 % lower after ER compared with EB (P<0·05). During the OGTT, serum glucose iAUC (P<0·001), serum insulin iAUC (P<0·05) and plasma NEFA tAUC (P<0·01) were greater during ER, but GLP-1 (P=0·161), GIP (P=0·473) and FGF21 (P=0·497) tAUC were similar between trials. These results demonstrate that severe energy restriction acutely impairs postprandial glycaemic control in lean men, despite reducing HOMA2-IR. Chronic intervention studies are required to elucidate the long-term effects of IER on indices of insulin sensitivity, particularly in the absence of weight loss.

Obese individuals exhibit a diminished muscle protein synthesis response to nutrient stimulation when compared with their lean counterparts. However, the effect of obesity on exercise-stimulated muscle protein synthesis remains unknown. Nine lean (23.5 ± 0.6 kg/m 2 ) and 8 obese (33.6 ± 1.2 kg/m 2 ) physically active young adults participated in a study that determined muscle protein synthesis and intracellular signaling at rest and following an acute bout of resistance exercise. Mixed muscle protein synthesis was determined by combining stable isotope tracer ([ 13 C 6 ]phenylalanine) infusion with serial biopsies of the vastus lateralis. A unilateral leg resistance exercise model was adopted so that resting and postexercise measurements of muscle protein synthesis could be obtained simultaneously. Obesity was associated with higher basal levels of serum insulin (P < 0.05), plasma triacylglycerol (P < 0.01), plasma cholesterol (P < 0.01), and plasma CRP (P < 0.01), as well as increased insulin resistance determined by HOMA-IR (P < 0.05). However, resting and postexercise rates of muscle protein synthesis were not significantly different between lean and obese participants (P = 0.644). Furthermore, resistance exercise stimulated muscle protein synthesis (~50% increase) in both groups (P < 0.001), with no difference between lean and obese (P = 0.809). Temporal increases in the phosphorylation of intracellular signaling proteins (AKT/4EBP1/p70S6K) were observed within the exercised leg (P < 0.05), with no differences between lean and obese. These findings suggest a normal anabolic response to muscle loading in obese young adults., (© 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Consuming excessive amounts of energy as dietary fat for several days or weeks can impair glycemic control and reduce insulin sensitivity in healthy adults. However, individuals who demonstrate binge eating behavior overconsume for much shorter periods of time; the metabolic consequences of such behavior remain unknown. The aim of this study was to determine the effect of a single day of high-fat overfeeding on whole-body insulin sensitivity. Fifteen young, healthy adults underwent an oral glucose tolerance test before and after consuming a high-fat (68% of total energy), high-energy (78% greater than daily requirements) diet for one day. Fasting and postprandial plasma concentrations of glucose, insulin, non-esterified fatty acids, and triglyceride were measured and the Matsuda insulin sensitivity index was calculated. One day of high-fat overfeeding increased postprandial glucose area under the curve (AUC) by 17.1% ( p < 0.0001) and insulin AUC by 16.4% ( p = 0.007). Whole-body insulin sensitivity decreased by 28% ( p = 0.001). In conclusion, a single day of high-fat, overfeeding impaired whole-body insulin sensitivity in young, healthy adults. This highlights the rapidity with which excessive consumption of calories through high-fat food can impair glucose metabolism, and suggests that acute binge eating may have immediate metabolic health consequences for the individual., Competing Interests: The authors declare no conflict of interest.

The purpose of the present study was to determine whether probiotic supplementation (Lactobacillus casei Shirota (LcS)) prevents diet-induced insulin resistance in human subjects. A total of seventeen healthy subjects were randomised to either a probiotic (n 8) or a control (n 9) group. The probiotic group consumed a LcS-fermented milk drink twice daily for 4 weeks, whereas the control group received no supplementation. Subjects maintained their normal diet for the first 3 weeks of the study, after which they consumed a high-fat (65 % of energy), high-energy (50 % increase in energy intake) diet for 7 d. Whole-body insulin sensitivity was assessed by an oral glucose tolerance test conducted before and after overfeeding. Body mass increased by 0·6 (SE 0·2) kg in the control group (P< 0·05) and by 0·3 (SE 0·2) kg in the probiotic group (P>0·05). Fasting plasma glucose concentrations increased following 7 d of overeating (control group: 5·3 (SE 0·1) v. 5·6 (SE 0·2) mmol/l before and after overfeeding, respectively, P< 0·05), whereas fasting serum insulin concentrations were maintained in both groups. Glucose AUC values increased by 10 % (from 817 (SE 45) to 899 (SE 39) mmol/l per 120 min, P< 0·05) and whole-body insulin sensitivity decreased by 27 % (from 5·3 (SE 1·4) to 3·9 (SE 0·9), P< 0·05) in the control group, whereas normal insulin sensitivity was maintained in the probiotic group (4·4 (SE 0·8) and 4·5 (SE 0·9) before and after overeating, respectively (P>0·05). These results suggest that probiotic supplementation may be useful in the prevention of diet-induced metabolic diseases such as type 2 diabetes.

In the present study, different MS methods for the determination of human muscle protein fractional synthesis rate (FSR) using [ring-(13)C6 ]phenylalanine as a tracer were evaluated. Because the turnover rate of human skeletal muscle is slow, only minute quantities of the stable isotopically labeled amino acid will be incorporated within the few hours of a typical laboratory experiment. GC combustion isotope ratio MS (GC-C-IRMS) has thus far been considered the 'gold' standard for the precise measurements of these low enrichment levels. However, advances in liquid chromatography-tandem MS (LC-MS/MS) and GC-tandem MS (GC-MS/MS) have made these techniques an option for human muscle FSR measurements. Human muscle biopsies were freeze dried, cleaned, and hydrolyzed, and the amino acids derivatized using either N-acetyl-n-propyl, phenylisothiocyanate, or N-methyl-N-(tert-butyldimethylsilyl)trifluoroacetamide (MTBSTFA) for GC-C-IRMS, LC-MS/MS, and GC-MS/MS analysis, respectively. A second derivative, heptafluorobutyric acid (HFBA), was also used for GC-MS/MS analysis as an alternative for MTBSTFA. The machine reproducibility or the coefficients of variation for delta tracer-tracee-ratio measurements (delta tracer-tracee-ratio values around 0.0002) were 2.6%, 4.1%, and 10.9% for GC-C-IRMS, LC-MS/MS, and GC-MS/MS (MTBSTFA), respectively. FSR determined with LC-MS/MS compared well with GC-C-IRMS and so did the GC-MS/MS when using the HFBA derivative (linear fit Y = 1.08 ± 0.10, X + 0.0049 ± 0.0061, r = 0.89 ± 0.01, P < 0.0001). In conclusion, (1) IRMS still offers the most precise measurement of human muscle FSR, (2) LC-MS/MS comes quite close and is a good alternative when tissue quantities are too small for GC-C-IRMS, and (3) If GC-MS/MS is to be used, then the HFBA derivative should be used instead of MTBSTFA, which gave unacceptably high variability., (Copyright © 2014 John Wiley & Sons, Ltd.)

Purpose: This study aimed to investigate the effect of protein ingestion on leg protein turnover and vastus lateralis muscle protein synthesis during bicycle exercise and recovery., Methods: Eight healthy males participated in two experiments in which they ingested either a carbohydrate solution (CHO) providing 0.49 g·kg(-1)·h(-1), or a carbohydrate and protein solution (CHO + P) providing 0.49 and 0.16 g·kg(-1)·h(-1), during 3 h of bicycle exercise and 3 h of recovery. Leg protein turnover was determined from stable isotope infusion (l-[ring-C6]phenylalanine), femoral-arterial venous blood sampling, and blood flow measurements. Muscle protein synthesis was calculated from the incorporation of l-[ring-C6]phenylalanine into protein., Results: Consuming protein during exercise increased leg protein synthesis and decreased net leg protein breakdown; however, protein ingestion did not increase protein synthesis within the highly active vastus lateralis muscle (0.029%·h(-1), ± 0.004%·h(-1), and 0.030%·h(-1), ± 0.003%·h(-1), in CHO and CHO + P, respectively; P = 0.88). In contrast, consuming protein, during exercise and recovery, increased postexercise vastus lateralis muscle protein synthesis by 51% ± 22% (0.070%·h(-1), ± 0.003%·h(-1), and 0.105%·h(-1), ± 0.013%·h(-1), in CHO and CHO+P, respectively; P < 0.01). Furthermore, leg protein net balance was negative during recovery with CHO intake, whereas positive leg protein net balance was achieved with CHO+P intake., Conclusions: We conclude that consuming protein during prolonged bicycle exercise does not increase protein synthesis within highly active leg muscles. However, protein intake may have stimulated protein synthesis within less active leg muscles and/or other nonmuscle leg tissue. Finally, protein supplementation, during exercise and recovery, enhanced postexercise muscle protein synthesis and resulted in positive leg protein net balance.

Purpose: To determine the effects of training with low muscle glycogen on exercise performance, substrate metabolism, and skeletal muscle adaptation., Methods: Fourteen well-trained cyclists were pair-matched and randomly assigned to HIGH- or LOW-glycogen training groups. Subjects performed nine aerobic training (AT; 90 min at 70% VO2max) and nine high-intensity interval training sessions (HIT; 8 × 5-min efforts, 1-min recovery) during a 3-wk period. HIGH trained once daily, alternating between AT on day 1 and HIT the following day, whereas LOW trained twice every second day, first performing AT and then, 1 h later, performing HIT. Pretraining and posttraining measures were a resting muscle biopsy, metabolic measures during steady-state cycling, and a time trial., Results: Power output during HIT was 297 ± 8 W in LOW compared with 323 ± 9 W in HIGH (P < 0.05); however, time trial performance improved by ∼10% in both groups (P < 0.05). Fat oxidation during steady-state cycling increased after training in LOW (from 26 ± 2 to 34 ± 2 μmol·kg−¹·min−¹, P < 0.01). Plasma free fatty acid oxidation was similar before and after training in both groups, but muscle-derived triacylglycerol oxidation increased after training in LOW (from 16 ± 1 to 23 ± 1 μmol·kg−¹·min−¹, P < 0.05). Training with low muscle glycogen also increased β-hydroxyacyl-CoA-dehydrogenase protein content (P < 0.01)., Conclusions: Training with low muscle glycogen reduced training intensity and, in performance, was no more effective than training with high muscle glycogen. However, fat oxidation was increased after training with low muscle glycogen, which may have been due to the enhanced metabolic adaptations in skeletal muscle.

Haemoglobin concentration ([Hb]), reticulocyte percentage (retic%) and OFF(hr score) are well-implemented screening tools to determine potential recombinant human erythropoietin (rHuEpo) abuse in athletes. Recently, the International Cycling Union implemented the OFF(z score) and the Hb(z score) in their anti-doping testing programme. The aim of this study is to evaluate the sensitivity of these indirect screening methods. Twenty-four human subjects divided into three groups with eight subjects each (G1; G2 and G3) were injected with rHuEpo. G1 and G2 received rHuEpo for a 4-week period with 2 weeks of "boosting" followed by 2 weeks of "maintenance" and a wash-out period of 3 weeks. G3 received rHuEpo for a 10-week period (boost = 3 weeks; maintenance = 7 weeks; wash out = 1 week). Three, seven and eight of the 24 volunteers exceeded the cut-off limits for OFF(hr score), [Hb] and retic%, respectively. One subject from G1, nobody from G2, and seven subjects from G3 exceeded the cut-off limit for Hb(z score.) In total, ten subjects exceeded the cut-off limit for the OFF(z score); two subjects from G1, two subjects from G2 and six subjects from G3. In total, indirect screening methods were able to indicate rHuEpo injections in 58% of subjects. However, 42% of our rHuEpo-injected subjects were not detected. It should be emphasised that the test frequency in real world anti-doping is far less than the present study, and hence the detection rate will be lower.

The purpose of this study was to investigate the possibility of a placebo effect from carbohydrate (CHO) intake during prolonged exercise. Ten endurance-trained male cyclists performed 3 experimental trials consisting of 120 min of steady-state cycling at 61% VO2max followed by a time trial (TT) lasting approximately 60 min. During exercise participants ingested either plain water (WAT), artificially colored and flavored water (PLA), or a 6% carbohydrate-electrolyte solution (CES). PLA and CES were produced with identical color and taste. To investigate the possibility of a placebo effect from CHO intake, participants were told that both flavored solutions contained CHO and that the purpose of the study was to compare CHO drinks with water. Mean power output during TT was 218 +/- 22 W in WAT, 219 +/- 17 W in PLA, and 242 +/- 27 W in CES. Performance times were 66.35 +/- 6.15, 65.94 +/- 5.56, and 59.69 +/- 2.87 min for WAT, PLA, and CES, respectively. Therefore, CES ingestion enhanced TT performance by 11.3% compared with WAT (p < .05) and 10.6% compared with PLA (p < .05), with no difference between PLA and WAT. In conclusion, during a prolonged test of cycling performance, in which participants were not fully informed of the test conditions, there was no placebo effect when participants believed they had ingested CHO. In contrast, the real effect of CHO intake was a 10.6% improvement in TT cycling performance.

Purpose: The purpose of the present study was to determine whether combined ingestion of moderate amounts of glucose plus fructose would result in higher rates of exogenous CHO oxidation compared with an isocaloric amount of glucose alone., Methods: Seven endurance-trained male cyclists performed three experimental trials consisting of 150 min of cycling at 65% VO(2max). Subjects ingested a CHO solution providing glucose (GLU) at an average rate of 0.8 g min(-1), glucose (0.54 g min(-1)) plus fructose (0.26 g min(-1)) (GLU + FRU), or plain water (WAT) during exercise. To quantify exogenous CHO oxidation, we prepared CHO solutions using corn-derived GLU and FRU, with a high natural abundance of 13C., Results: Peak exogenous CHO oxidation rates were not significantly different between GLU and GLU + FRU (0.60 +/- 0.06 and 0.57 +/- 0.06 g min(-1), respectively). Furthermore, average exogenous CHO oxidation rates during the final 90 min of exercise were not significantly different between GLU and GLU + FRU (0.58 +/- 0.05 and 0.56 +/- 0.06 g min(-1), respectively)., Conclusion: The present study demonstrates that ingesting moderate amounts of glucose plus fructose does not increase exogenous CHO oxidation above that of an isocaloric amount of glucose alone.

Purpose: To evaluate the efficacy of using combined glucose and fructose (GF) ingestion as a means to stimulate short-term (4 h) postexercise muscle glycogen synthesis compared to glucose only (G)., Methods: On two separate occasions, six endurance-trained men performed an exhaustive glycogen-depleting exercise bout followed by a 4-h recovery period. Muscle biopsy samples were obtained from the vastus lateralis muscle at 0, 1, and 4 h after exercise. Subjects ingested carbohydrate solutions containing G (90 g x h(-1)) or GF (G = 60 g x h(-1); F = 30 g x h(-1)) commencing immediately after exercise and every 30 min thereafter., Results: Immediate postexercise muscle glycogen concentrations were similar in both trials (G = 128 +/- 25 mmol x kg(-1) dry muscle (dm) vs GF = 112 +/- 16 mmol x kg(-1) dm; P > 0.05). Total glycogen storage during the 4-h recovery period was 176 +/- 33 and 155 +/- 31 mmol x kg(-1) dm for G and GF, respectively (G vs GF, P > 0.05). Hence, mean muscle glycogen synthesis rates during the 4-h recovery period did not differ between the two conditions (G = 44 +/- 8 mmol x kg(-1) dm x h(-1) vs GF = 39 +/- 8 mmol x kg(-1) dm x h(-1), P > 0.05). Plasma glucose and serum insulin responses during the recovery period were similar in both conditions, although plasma lactate concentrations were significantly elevated during GF compared to G (by approximately 0.8 mmol x L(-1), P < 0.05)., Conclusions: Glucose and glucose/fructose (2:1 ratio) solutions, ingested at a rate of 90 g x h(-1), are equally effective at restoring muscle glycogen in exercised muscles during the recovery from exhaustive exercise.

Background: Green tea consumption is reportedly associated with various health-promoting properties. For example, it has been shown to promote fat oxidation in humans at rest and to prevent obesity and improve insulin sensitivity in mice., Objective: We investigated the effects of acute ingestion of green tea extract (GTE) on glucose tolerance and fat oxidation during moderate-intensity exercise in humans., Design: Two studies were performed, both with a counter-balanced crossover design. In study A, 12 healthy men performed a 30-min cycling exercise at 60% of maximal oxygen consumption (VO2max) before and after supplementation. In study B, 11 healthy men took an oral-glucose-tolerance test before and after supplementation. In the 24-h period before the experimental trials, participants ingested 3 capsules containing either GTE (total: 890 +/- 13 mg polyphenols and 366 +/- 5 mg EGCG) or a corn-flour placebo (total: 1729 +/- 22 mg)., Results: Average fat oxidation rates were 17% higher after ingestion of GTE than after ingestion of placebo (0.41 +/- 0.03 and 0.35 +/- 0.03 g/min, respectively; P < 0.05). Moreover, the contribution of fat oxidation to total energy expenditure was also significantly higher, by a similar percentage, after GTE supplementation. The insulin area under the curve decreased in both the GTE and placebo trials (3612 +/- 301 and 4280 +/- 309 microIU/dL . 120 min, respectively; P < 0.01), and there was a concomitant increase of 13% in insulin sensitivity., Conclusions: Acute GTE ingestion can increase fat oxidation during moderate-intensity exercise and can improve insulin sensitivity and glucose tolerance in healthy young men.

An important element in the measurement of energy budgets of free-living animals is the estimation of energy costs during locomotion. Using humans as a particularly tractable model species, we conducted treadmill experiments to test the validity of tri-axial accelerometry loggers, designed for use with animals in the field, to estimate rate of oxygen consumption (VO2: an indirect measure of metabolic rate) and speed during locomotion. The predictive power of overall dynamic body acceleration (ODBA) obtained from loggers attached to different parts of the body was compared to that of heart rate (fH). When subject identity was included in the statistical analysis, ODBA was a good, though slightly poorer, predictor of VO2 and speed during locomotion on the flat (mean of two-part regressions: R2=0.91 and 0.91, from a logger placed on the neck) and VO2 during gradient walking (single regression: R2=0.77 from a logger placed on the upper back) than was fH (R2=0.96, 0.94, 0.86, respectively). For locomotion on the flat, ODBA was still a good predictor when subject identity was replaced by subject mass and height (morphometrics typically obtainable from animals in the field; R2=0.92 and 0.89) and a slightly better overall predictor than fH (R2=0.92 and 0.85). For gradient walking, ODBA predicted VO2 more accurately than before (R2=0.83) and considerably better than did fH (R2=0.77). ODBA and fH combined were the most powerful predictor of VO2 and speed during locomotion. However, ODBA alone appears to be a good predictor and suitable for use in the field in particular, given that accelerometry traces also provide information on the timing, frequency and duration of locomotion events, and also the gait being used.