Nicotinamide adenine dinucleotide (NAD + ) is an essential metabolite for energy metabolism that is involved in key cellular processes including glycolysis, the Krebs cycle, DNA repair, and other metabolic reactions within the cell (Canto et al., 2015;McReynolds et al., 2020). NAD + levels have been identified to decline during aging, with alterations in NAD + homeostasis being found in virtually all age-related diseases, including neurodegeneration, diabetes, and cancer. Nicotinamide phosphoribosyltransferase (NAMPT) is a rate-limiting enzyme in the NAD + biosynthetic pathway that exists

Purpose: The aim of this study was to investigate the influence of manipulating hypoxic severity with low-intensity exercise on glucose regulation in healthy overweight adults.Methods: In a randomized crossover design, 14 males with overweight (age: 27 ± 5 years; body mass index (BMI) 27.1 ± 1.8 kg⋅m2) completed three exercise trials involving 60 min aerobic exercise cycling at 90% lactate threshold in normoxia (NM, FiO2 = 20.9%), moderate hypoxia (MH, FiO2 = 16.5%) and high hypoxia (HH, FiO2 = 14.8%). A post-exercise oral glucose tolerance test (OGTT) was performed. Venous blood samples were analyzed for incremental area under the curve (iAUC), plasma glucose and insulin, as well as exerkine concentrations (plasma apelin and fibroblast growth factor 21 [FGF-21]) pre- and post-exercise. A 24-h continuous glucose monitoring (CGM) was used to determine interstitial glucose concentrations. Heart rate, oxygen saturation (SpO2) and perceptual measures were recorded during exercise.Results: Post-exercise OGTT iAUC for plasma glucose and insulin concentrations were lower in MH vs. control (p = 0.02). Post-exercise interstitial glucose iAUC, plasma apelin and FGF-21 were not different between conditions. Heart rate was higher in HH vs. NM and MH, and MH vs. NM (p < 0.001), while SpO2 was lower in HH vs. NM and MH, and MH vs. NM (p < 0.001). Overall perceived discomfort and leg discomfort were higher in HH vs. NM and MH (p < 0.05), while perceived breathing difficulty was higher in HH vs. NM only (p = 0.003).Conclusion: Compared to higher hypoxic conditions, performing acute aerobic-based exercise under moderate hypoxia provided a more effective stimulus for improving post-exercise glucose regulation while concomitantly preventing excessive physiological and perceptual stress in healthy overweight adults.

Obesity is a major global health issue and a primary risk factor for metabolic-related disorders. While physical inactivity is one of the main contributors to obesity, it is a modifiable risk factor with exercise training as an established non-pharmacological treatment to prevent the onset of metabolic-related disorders, including obesity. Exposure to hypoxia via normobaric hypoxia (simulated altitude via reduced inspired oxygen fraction), termed hypoxic conditioning, in combination with exercise has been increasingly shown in the last decade to enhance blood glucose regulation and decrease the body mass index, providing a feasible strategy to treat obesity. However, there is no current consensus in the literature regarding the optimal combination of exercise variables such as the mode, duration, and intensity of exercise, as well as the level of hypoxia to maximize fat loss and overall body compositional changes with hypoxic conditioning. In this narrative review, we discuss the effects of such diverse exercise and hypoxic variables on the systematic and myocellular mechanisms, along with physiological responses, implicated in the development of obesity. These include markers of appetite regulation and inflammation, body conformational changes, and blood glucose regulation. As such, we consolidate findings from human studies to provide greater clarity for implementing hypoxic conditioning with exercise as a safe, practical, and effective treatment strategy for obesity.

Acute physiological, perceptual and biomechanical consequences of manipulating both exercise intensity and hypoxic exposure during treadmill running were determined. On separate days, eleven trained individuals ran for 45 s (separated by 135 s of rest) on an instrumented treadmill at seven running speeds (8, 10, 12, 14, 16, 18 and 20 km.h −1 ) in normoxia (NM, FiO 2 = 20.9%), moderate hypoxia (MH, FiO 2 = 16.1%), high hypoxia (HH, FiO 2 = 14.1%) and severe hypoxia (SH, FiO 2 = 13.0%). Running mechanics were collected over 20 consecutive steps (i.e. after running ∼25 s), with concurrent assessment of physiological (heart rate and arterial oxygen saturation) and perceptual (overall perceived discomfort, difficulty breathing and leg discomfort) responses. Two-way repeated-measures ANOVA (seven speeds × four conditions) were used. There was a speed × condition interaction for heart rate (p = 0.045, ηp 2 = 0.22), with lower values in NM, MH and HH compared to SH at 8 km.h −1 (125 ± 12, 125 ± 11, 128 ± 12 vs 132 ± 10 b.min −1 ). Overall perceived discomfort (8 and 16 km.h −1 ; p = 0.019 and p = 0.007, ηp 2 = 0.21, respectively) and perceived difficulty breathing (all speeds; p = 0.023, ηp 2 = 0.37) were greater in SH compared to MH, whereas leg discomfort was not influenced by hypoxic exposure. Minimal difference was observed in the twelve kinetics/kinematics variables with hypoxia (p > 0.122; η p 2 = 0.19). Running at slower speeds in combination with severe hypoxia elevates physiological and perceptual responses without a corresponding increase in ground reaction forces. Highlights. The extent to which manipulating hypoxia severity (between normoxia and severe hypoxia) and running speed (from 8 to 20 km.h −1 ) influence acute physiological and perceptual responses, as well as kinetic and kinematic adjustments during treadmill running was determined. . Running at slower speeds in combination with severe hypoxia elevates heart rate, while this effect was not apparent at faster speeds. . Arterial oxygen saturation was increasingly lower as running speed and hypoxic severity increased. . Overall perceived discomfort (8 and 16 km.h −1 ) and perceived difficulty breathing (all speeds) were lower in moderate hypoxia than in severe hypoxia, whereas leg discomfort remained unchanged with hypoxic exposure.

Purpose: To identify the effects of leucine, β-hydroxy β-methylbutyrate (HMB) and branched chain amino acid (BCAA) on post-exercise cytokine responses in females and males. Methods: Males (n=53) and females (n=37) completed 100 drop jumps and consumed either no supplement, leucine (3g/d), HMB (3g/d) or BCAA (4.5g/d) from 1d pre to 14d post-exercise. Muscle soreness, squat jumps, chair rises and creatine kinase (CK) were measured at pre, post, 24h, 48h, 7 and 14d. Blood lactate (pre, post), 10 cytokines (pre, 24h, 48h, 7d) and oestradiol (pre, 7d) were also measured. Results: Without supplementation post-exercise, soreness was induced in both males (6-fold) and females (5-fold). With supplementation, there were no increases in CK or oestradiol in females and no impact on muscle soreness, performance, or function in both sexes. In males, CK was elevated in untreated (48%) and leucine (69%) conditions vs baseline, but these were suppressed with HMB and BCAA. IL-7 was elevated in females vs males at baseline (6.3-fold), leucine increased IL-7 concentrations in females at 24h (17.0-fold), 48h (5.1-fold) vs males. With HMB, TNFr1-α increased in females at 24h (2.2-fold), 48h (2.3-fold) and 7d (2.3-fold) vs males. In males with BCAA, TNFr1-α decreased (P=0.06) from pre to 24h (6.8-fold), then increased (P<0.05) from 24 to 48h (8.0-fold). Conclusion: Although supplements were without effect on soreness following exercise, the cytokine response was evoked by exercise and impacted significantly by leucine, HMB and BCAA in females vs males. This improved cytokine response in females could lead to improved resistance to damage.