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Metabolomic profiles are reflective of hypoxia-induced insulin resistance during exercise in healthy young adult males.

ABSTRACT: Hypoxia-induced insulin resistance appears to suppress exogenous glucose oxidation during metabolically matched aerobic exercise during acute (<8 h) high-altitude (HA) exposure. However, a better understanding of this metabolic dysregulation is needed to identify interventions to mitigate these effects. The objective of this study was to determine if differences in metabolomic profiles during exercise at sea level (SL) and HA are reflective of hypoxia-induced insulin resistance. Native lowlanders (n = 8 males) consumed 145 g (1.8 g/min) of glucose while performing 80-min of metabolically matched treadmill exercise at SL (757 mmHg) and HA (460 mmHg) after 5-h exposure. Exogenous glucose oxidation and glucose turnover were determined using indirect calorimetry and dual tracer technique ([¹³C]glucose and [6,6-²H₂]glucose). Metabolite profiles were analyzed in serum as change (Δ), calculated by subtracting postprandial/exercised state SL (ΔSL) and HA (ΔHA) from fasted, rested conditions at SL. Compared with SL, exogenous glucose oxidation, glucose rate of disappearance, and glucose metabolic clearance rate (MCR) were lower (P < 0.05) during exercise at HA. One hundred and eighteen metabolites differed between ΔSL and ΔHA (P < 0.05, Q < 0.10). Differences in metabolites indicated increased glycolysis, tricarboxylic acid cycle, amino acid catabolism, oxidative stress, and fatty acid storage, and decreased fatty acid mobilization for ΔHA. Branched-chain amino acids and oxidative stress metabolites, Δ3-methyl-2-oxobutyrate (r = -0.738) and Δγ-glutamylalanine (r = -0.810), were inversely associated (P < 0.05) with Δexogenous glucose oxidation. Δ3-Hydroxyisobutyrate (r = -0.762) and Δ2-hydroxybutyrate/2-hydroxyisobutyrate (r = -0.738) were inversely associated (P < 0.05) with glucose MCR. Coupling global metabolomics and glucose kinetic data suggest that the underlying cause for diminished exogenous glucose oxidative capacity during aerobic exercise is acute hypoxia-mediated peripheral insulin resistance.

SUBMITTER: Margolis LM

PROVIDER: S-EPMC8321788 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The primary objective of the current study was to determine the effect of moderate normobaric hypoxia exposure during constant load cycling on post-exercise energy metabolism recorded in normoxia. Indirect calorimetry was used to examine whole body substrate oxidation before, during, 40-60 min post, and 22 h after performing 60 min of cycling exercise at two different fractions of inspired oxygen (FIO2): (i) FIO2 = 0.2091 (normoxia) and (ii) FIO2 = 0.15 (hypoxia). Seven active healthy male participants (26 ± 4 years of age) completed both experimental trials in randomized order with a 7-day washout period to avoid carryover effects between conditions. Resting energy expenditure was initially elevated following cycling exercise in normoxia and hypoxia (Δ 0.14 ± 0.05, kcal min-1, p = 0.037; Δ 0.19 ± 0.03 kcal min-1, p < 0.001, respectively), but returned to baseline levels the next morning in both conditions. Although, the same absolute workload was used in both environmental conditions (157 ± 10 W), a shift in resting substrate oxidation occurred after exercise performed in hypoxia while post-exercise measurements were similar to baseline after cycling exercise in normoxia. The additional metabolic stress of hypoxia exposure was sufficient to increase the rate of lipid oxidation (Δ 42 ± 11 mg min-1, p = 0.019) and tended to suppress carbohydrate oxidation (Δ -55 ± 26 mg min-1, p = 0.076) 40-60 min post-exercise. This shift in substrate oxidation persisted the next morning, where lipid oxidation remained elevated (Δ 9 ± 3 mg min-1, p = 0.0357) and carbohydrate oxidation was suppressed (Δ -22 ± 6 mg min-1, p = 0.019). In conclusion, prior exercise performed under moderate normobaric hypoxia alters post-exercise energy metabolism. This is an important consideration when evaluating the metabolic consequences of hypoxia exposure during prolonged exercise, and future studies should evaluate its role in the beneficial effects of intermittent hypoxia training observed in persons with obesity and insulin resistance.

Project description:BackgroundInadequate sleep is associated with many detrimental health effects, including increased risk of developing insulin resistance and type 2 diabetes. These effects have been associated with changes to the skeletal muscle transcriptome, although this has not been characterised in response to a period of sleep restriction. Exercise induces a beneficial transcriptional response within skeletal muscle that may counteract some of the negative effects associated with sleep restriction. We hypothesised that sleep restriction would down-regulate transcriptional pathways associated with glucose metabolism, but that performing exercise would mitigate these effects.Methods20 healthy young males were allocated to one of three experimental groups: a Normal Sleep (NS) group (8 h time in bed per night (TIB), for five nights (11 pm - 7 am)), a Sleep Restriction (SR) group (4 h TIB, for five nights (3 am - 7 am)), and a Sleep Restriction and Exercise group (SR+EX) (4 h TIB, for five nights (3 am - 7 am) and three high-intensity interval exercise (HIIE) sessions (performed at 10 am)). RNA sequencing was performed on muscle samples collected pre- and post-intervention. Our data was then compared to skeletal muscle transcriptomic data previously reported following sleep deprivation (24 h without sleep).ResultsGene set enrichment analysis (GSEA) indicated there was an increased enrichment of inflammatory and immune response related pathways in the SR group post-intervention. However, in the SR+EX group the direction of enrichment in these same pathways occurred in the opposite directions. Despite this, there were no significant changes at the individual gene level from pre- to post-intervention. A set of genes previously shown to be decreased with sleep deprivation was also decreased in the SR group, but increased in the SR+EX group.ConclusionThe alterations to inflammatory and immune related pathways in skeletal muscle, following five nights of sleep restriction, provide insight regarding the transcriptional changes that underpin the detrimental effects associated with sleep loss. Performing three sessions of HIIE during sleep restriction attenuated some of these transcriptional changes. Overall, the transcriptional alterations observed with a moderate period of sleep restriction were less evident than previously reported changes following a period of sleep deprivation.

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Metabolomic profiles are reflective of hypoxia-induced insulin resistance during exercise in healthy young adult males.

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