Exercise increases TCA intermediate concentrations during low-calorie diet independent of insulin resistance among women with obesity.

Tricarboxylic acid cycle intermediates (TCAi) have been proposed to act as myokines that influence energy metabolism. We determined if 2-weeks of low-calorie diet with interval exercise (LCD + INT) would increase TCAi more than a low-calorie diet (LCD). Twenty-three women were randomized to 2-weeks of LCD (n = 12, 48.4 ± 2.5 years, 37.8 ± 1.5 kg/m2, ~1200 kcal/d) or LCD + INT (n = 11, 47.6 ± 4.3 years, 37.9 ± 2.3 kg/m2; 60 min/d supervised INT of 3 min 90% & 50% HRpeak). TCAi and amino acids (AA) were measured at 0 min of a 75 g OGTT, while glucose, insulin, and FFA were obtained at 0, 30, 60, 90, 120, and 180 min to assess total area under the curve (tAUC180min) and insulin resistance (IR; tAUC180min of Glucose × Insulin). Fuel use (indirect calorimetry) was also collected at 0, 60, 120, and 180 min as was fitness (VO2peak) and body composition (BodPod). Treatments reduced weight (p < 0.001), fasting RER (p = 0.01), and IR (p = 0.03), although LCD + INT increased VO2peak (p = 0.02) and maintained RER tAUC180min (p = 0.05) versus LCD. Treatments increased FFA tAUC180min (p = 0.005), cis-aconitate, isocitrate, and succinate (p ≤ 0.02), as well as reduced phenylalanine and tryptophan, cysteine (p ≤ 0.005). However, LCD + INT increased malate, citrate, α-ketoglutarate, and alanine more than LCD (p ≤ 0.04). Thus, INT enhanced LCD effects on some TCAi in women with obesity independent of IR.

The effects of betaine supplementation on fluid balance and heat tolerance during passive heat stress in men.

INTRODUCTION: Consuming intracellular osmolytes, like betaine (BET), may attenuate symptoms of heat stress. The purpose of this study was to examine the effects of BET supplementation on fluid balance and heat tolerance after a 7-day loading period and during passive heat exposure. METHODS: A double-blind, placebo controlled, crossover study compared BET or placebo consumption (50 mg·kg-1 , twice daily) for 7 days in young, recreationally active men (N = 11). RESULTS: During the loading period, no significant interactions were found for any marker of fluid balance between or within conditions. During heat exposure, significant time effects but no condition x time interactions, were found for plasma characteristics (i.e., volume, osmolality, sodium, albumin, and total protein). Plasma volume was significantly increased by min 30 in both conditions (PLA: +6.9. ± 5.0%, BET: +10.2 ± 7.4%) and remained elevated for the remainder of the experimental trial, but was not significantly different between conditions. After 60 min of passive heat exposure, both conditions experienced a similar increase in core temperature (PLA: +0.32 ± 0.22°C, BET: +0.31 ± 0.21°C; p = 0.912). CONCLUSIONS: Supplemental BET did not improve markers of fluid balance or heat tolerance during 7 days of loading or during passive heat exposure.

Plasma LEAP-2 Following a Low-Calorie Diet with or without Interval Exercise in Women with Obesity.

Liver-expressed antimicrobial peptide-2 (LEAP-2) is associated with caloric intake and glucose metabolism. Purpose: Assess if a low-calorie diet with interval exercise (LCD+INT) raises LEAP-2 more than LCD in relation to appetite and cardiometabolic health. Methods: Women with obesity were randomized to either 2 weeks of LCD (n = 13, ~1200 kcal/d) or LCD+INT (n = 12; 60 min/d) of INT at 3 min of 90% and 50% HRpeak, respectively. LEAP-2 and acylated ghrelin (AG) were measured at 0, 30, and 60 min, while glucose, insulin, C-peptide, and free fatty acids (FFA) were obtained up to 180 min of a 75 g OGTT. Fasting and 120 min OGTT appetite were assessed via visual analog scales. Results: LCD reduced the BMI (p < 0.001) compared with LCD+INT, but only LCD+INT increased the VO2 max (p = 0.04). Treatments reduced fasting LEAP-2 (p = 0.05), but only LCD increased LEAP-2 iAUC60 min (p = 0.06) and post-prandial LEAP-2 stimulation (p = 0.02). Higher post-LEAP-260 min tended to relate to a lower desire to eat 120 min of sweet (r = 0.40, p = 0.07) and salty foods (r = 0.41, p = 0.06), as well as lower AG30 min (r = -0.51, p = 0.01) and higher FFA iAUC180 min (r = 0.56, p = 0.007) post-treatment. Conclusion: LCD, with or without INT, reduced fasting LEAP-2, but only LCD raised post-prandial LEAP-2. How diet and exercise impact LEAP-2 for lower chronic disease risk awaits further investigation.

Extracellular vesicles and insulin-mediated vascular function in metabolic syndrome.

Metabolic Syndrome (MetS) raises cardiovascular disease risk. Extracellular vesicles (EVs) have emerged as important mediators of insulin sensitivity, although few studies on vascular function exist in humans. We determined the effect of insulin on EVs in relation to vascular function. Adults with MetS (n = 51, n = 9 M, 54.8 ± 1.0 years, 36.4 ± 0.7 kg/m2 , ATPIII: 3.5 ± 0.1 a.u., VO2 max: 22.1 ± 0.6 ml/kg/min) were enrolled in this cross-sectional study. Peripheral insulin sensitivity (M-value) was determined during a euglycemic clamp (40 mU/m2 /min, 90 mg/dl), and blood was collected for EVs (CD105+, CD45+, CD41+, TX+, and CD31+; spectral flow cytometry), inflammation, insulin, and substrates. Central hemodynamics (applanation tonometry) was determined at 0 and 120 min via aortic waveforms. Pressure myography was used to assess insulin-induced arterial vasodilation from mouse 3rd order mesenteric arteries (100-200 µm in diameter) at 0.2, 2 and 20 nM of insulin with EVs from healthy and MetS adults. Adults with MetS had low peripheral insulin sensitivity (2.6 ± 0.2 mg/kg/min) and high HOMA-IR (4.7 ± 0.4 a.u.) plus Adipose-IR (13.0 ± 1.3 a.u.). Insulin decreased total/particle counts (p < 0.001), CD45+ EVs (p = 0.002), AIx75 (p = 0.005) and Pb (p = 0.04), FFA (p < 0.001), total adiponectin (p = 0.006), ICAM (p = 0.002), and VCAM (p = 0.03). Higher M-value related to lower fasted total EVs (r = -0.40, p = 0.004) while higher Adipose-IR associated with higher fasted EVs (r = 0.42, p = 0.004) independent of VAT. Fasting CD105+ and CD45+ derived total EVs correlated with fasting AIx75 (r = 0.29, p < 0.05) and Pb (r = 0.30, p < 0.05). EVs from MetS participants blunted insulin-induced vasodilation in mesenteric arteries compared with increases from healthy controls across insulin doses (all p < 0.005). These data highlight EVs as potentially novel mediators of vascular insulin sensitivity and disease risk.

Nutrition Interactions With Exercise Training on Endothelial Function.

Exercise is advised to improve overall cardiovascular health and endothelial function. However, the role of nutrition on this exercise-induced endothelial adaptation is not clear. Here, we hypothesize that nutrients interact with exercise to influence endothelial function and chronic disease risk.

Early chronotype with metabolic syndrome favours resting and exercise fat oxidation in relation to insulin-stimulated non-oxidative glucose disposal.

NEW FINDINGS: What is the central question of this study? Chronotype reflects differences in circadian-mediated metabolic and hormonal profiles. But, does resting and/or exercise fuel use differ in early versus late chronotype as it relates to insulin sensitivity? What are the main finding and its importance? Early chronotypes with metabolic syndrome utilized more fat during rest and exercise independent of aerobic fitness when compared with late chronotypes. Early chronotypes were also more physically active throughout the day. Greater fat use was related to non-oxidative glucose disposal. These findings suggest that early chronotypes have differences in fuel selection that associate with type 2 diabetes risk. ABSTRACT: Early chronotypes (ECs) are often insulin-sensitive, in part, due to physical activity behaviour. It is unclear, however, if chronotypes differ in resting and/or exercise fuel oxidation in relation to insulin action. Using the Morningness-Eveningness Questionnaire (MEQ), adults with metabolic syndrome (ATP III criteria) were classified as EC (MEQ = 63.7 ± 0.9, n = 24 (19F), 54.2 ± 1.2 years) or late chronotype (LC; MEQ = 47.2 ± 1.4, n = 27 (23F), 55.3 ± 1.5 years). Carbohydrate (CHO) and fat oxidation (FOX, indirect calorimetry) were determined at rest, 55% and 85% V ̇ O 2 max ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{max}}}$ , along with heart rate and rating of perceived exertion. Physical activity patterns (accelerometers), body composition (DXA) and insulin sensitivity (clamp, 40 mU/m2 /min, 90 mg/dl) with an indirect calorimetry for non-oxidative glucose disposal (NOGD) were also determined. While demographics were similar, ECs had higher V ̇ O 2 max ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{max}}}$ (P = 0.02), NOGD (P < 0.001) and resting FOX (P = 0.02) than LCs. Both groups increased CHO reliance during exercise at 55% and 85% V ̇ O 2 max ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{max}}}$ (test effect, P < 0.01) from rest, although ECs used more fat (group effect, P < 0.01). ECs had lower sedentary behaviour and more physical activity during morning/midday (both, P < 0.05). FOX at 55% V ̇ O 2 max ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{max}}}$ correlated with V ̇ O 2 max ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{max}}}$ (r = 0.425, P = 0.004) whereas FOX at 85% V ̇ O 2 max ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{max}}}$ related to NOGD (r = 0.392, P = 0.022). ECs with metabolic syndrome used more fat in relation to insulin-stimulated NOGD.

Betaine Supplementation May Improve Heat Tolerance: Potential Mechanisms in Humans.

Betaine has been demonstrated to increase tolerance to hypertonic and thermal stressors. At the cellular level, intracellular betaine functions similar to molecular chaperones, thereby reducing the need for inducible heat shock protein expression. In addition to stabilizing protein conformations, betaine has been demonstrated to reduce oxidative damage. For the enterocyte, during periods of reduced perfusion as well as greater oxidative, thermal, and hypertonic stress (i.e., prolonged exercise in hot-humid conditions), betaine results in greater villi length and evidence for greater membrane integrity. Collectively, this reduces exercise-induced gut permeability, protecting against bacterial translocation and endotoxemia. At the systemic level, chronic betaine intake has been shown to reduce core temperature, all-cause mortality, markers of inflammation, and change blood chemistry in several animal models when exposed to heat stress. Despite convincing research in cell culture and animal models, only one published study exists exploring betaine's thermoregulatory function in humans. If the same premise holds true for humans, chronic betaine consumption may increase heat tolerance and provide another avenue of supplementation for those who find that heat stress is a major factor in their work, or training for exercise and sport. Yet, this remains speculative until data demonstrate such effects in humans.

The effect of cold ambient temperature and preceding active warm-up on lactate kinetics in female cyclists and triathletes.

The aim of this study was to evaluate the effect of cold ambient temperature on lactate kinetics with and without a preceding warm-up in female cyclists/triathletes. Seven female cyclists/triathletes participated in this study. The randomized, crossover study included 3 experimental visits that comprised the following conditions: (i) thermoneutral temperature (20 °C; NEU); (ii) cold temperature (0 °C) with no active warm-up (CNWU); and (iii) cold temperature (0 °C) with 25-min active warm-up (CWU). During each condition, participants performed a lactate threshold (LT) test followed by a time to exhaustion trial at 120% of the participant's peak power output (PPO) as determined during prior peak oxygen consumption testing. Power output at LT with CNWU was 10.2% ± 2.6% greater than with NEU, and the effect was considered very likely small (effect size (ES) = 0.59, 95%-99% likelihood). Power output at LT with CNWU was 4.2% ± 5.4% greater than with CWU; however, the effect was likely trivial (ES = 0.25, 75%-95% likelihood). At LT, there were no significant differences between interventions groups in oxygen consumption, blood lactate concentration, heart rate, or rating of perceived exertion. Time to exhaustion at 120% at PPO was 11% longer with CNWU than with CWU (ES = 0.62, respectively), and this effect was likely small. These findings suggest that power output at LT was higher in CNWU compared with NEU. Additionally, time to exhaustion at 120% of PPO was higher in CNWU compared with CWU and no different than NEU; these differences likely result in a small improvement in performance with CNWU versus CWU and NEU.

Adipose Lipolysis Unchanged by Preexercise Carbohydrate Regardless of Glycemic Index.

PURPOSE: This study aimed to determine the effect of preexercise carbohydrate of different glycemic indices on subcutaneous abdominal adipose tissue (SCAAT) metabolism and running performance. METHODS: Ten trained male runners completed three experimental trials consisting of 30 min at 60% maximal oxygen consumption, 30 min at 75% maximal oxygen consumption, and a 5-km time trial. Thirty minutes before exercise, participants consumed one of three beverages: 1) 75 g low glycemic index modified starch supplement (UCAN), 2) 75 g high glycemic index glucose-based supplement (G), or 3) a flavor-matched noncaloric placebo (PL). SCAAT lipolysis was assessed via microdialysis. RESULTS: Before exercise, blood glucose and insulin were elevated with G versus PL (+53.0 ± 21.3 mg·dL (mean ± SD), P < 0.0001; +33.9 ± 11.0 µU·mL, P < 0.0001) and G versus UCAN (+36.6 ± 24.9 mg·dL, P < 0.0001; +25.2 ± 11.0 µU·mL, P < 0.0001), respectively. Fat oxidation was attenuated, and carbohydrate oxidation increased before exercise with G versus PL (-0.06 ± 0.06 g·min, P = 0.005; +0.18 ± 0.07 g·min, P < 0.0001) and G versus UCAN (-0.06 ± 0.05 g·min, P = 0.004; +0.18 ± 0.14 g·min, P < 0.0001). However, there were no differences in SCAAT lipolysis at rest or during running at either exercise intensity. Also, there was no effect of treatment on running performance. CONCLUSIONS: Preexercise carbohydrate lowers fat oxidation and increases carbohydrate oxidation, and these effects are attenuated with low glycemic index carbohydrate. However, these changes are not the result of alterations in SCAAT lipolysis, nor do they affect running performance.