Benjamin J. Ryan

We provide the first direct assessment of the plasma volume (PV) and volume regulatory responses to a practical, fixed-workload heat acclimation (HA) protocol in men and women. Maximal oxygen uptake was not influenced by HA, sex, or individual changes in PV. In women, progesterone was correlated with PV changes following HA.

Existing literature suggests cold habituation is capable of cross-adapting submaximal exercise ventilatory, cardiac, and catecholamine responses with normobaric hypoxia. No data exists investigating cold-to-altitude cross adaptation within real-world applicable conditions of hypobaric hypoxia. This investigation suggests that habituation to repeated cold-water immersion does not advantageously cross adapt those subsequently exposed to hypobaric hypoxia.

We developed a novel exercise with overdressing protocol for heat acclimation and validated it using two randomized crossover trials. Five sessions of exercise with overdressing in a gym-like environment significantly lowered resting core temperature and peak core temperature, skin temperature, and heart rate during exercise in the heat. These adaptations were superior compared with five sessions of control exercise. This practical exercise with overdressing protocol induces heat acclimation without requiring hot weather.

We evaluated sex differences in the magnitude and time course of physiological adaptations to heat stress using a generalizable and practical protocol (i.e., standardized work rate in the heat). Men and women had similar adaptations in core temperature, despite greater sweating in the men. We also report for the first time that intracellular heat shock protein 72 increases similarly in males and females during heat acclimation.

In this study, we first characterized systemic hypercapnia and headache severity during graded CO₂ exposures (sequential 12-min stages of 0%, 2%, 4%, 6%, and 8% inspired CO₂). Using a randomized, double-blind, crossover trial, we then showed that prophylactic treatment with 400 mg caffeine mitigates systemic hypercapnia and headache during graded CO₂ exposure. Overall, these novel findings establish caffeine as the first evidence-based countermeasure to mitigate adverse effects associated with CO₂ exposure.

Aim: To examine factors underlying why most, but not all, adults with obesity exhibit impaired insulin‐mediated glucose uptake, we compared: (1) adipose tissue fatty acid (FA) release, (2) skeletal muscle lipid droplet (LD) characteristics, and (3) insulin signalling events, in skeletal muscle of adults with obesity with relatively high versus low insulin‐mediated glucose uptake.Methods: Seventeen adults with obesity (BMI: 36 ± 3 kg/m²) completed a 2 h hyperinsulinemic–euglycemic clamp with stable isotope tracer infusions to measure glucose rate of disappearance (glucose Rd) and FA rate of appearance (FA Ra). Skeletal muscle biopsies were collected at baseline and 30 min into the insulin infusion. Participants were stratified into HIGH (n = 7) and LOW (n = 10) insulin sensitivity cohorts by their glucose Rd during the hyperinsulinemic clamp (LOW< 400; HIGH >550 nmol/kgFFM/min/[μU/mL]).Results: Insulin‐mediated suppression of FA Ra was lower in LOW compared with HIGH (p < 0.01). In skeletal muscle, total intramyocellular lipid content did not differ between cohorts. However, the size of LDs in the subsarcolemmal region (SS) of type II muscle fibres was larger in LOW compared with HIGH (p = 0.01). Additionally, insulin receptor‐β (IRβ) interactions with regulatory proteins CD36 and Fyn were lower in LOW versus HIGH (p < 0.01), which aligned with attenuated insulin‐mediated Tyr phosphorylation of IRβ and downstream insulin‐signalling proteins in LOW.Conclusion: Collectively, reduced ability for insulin to suppress FA mobilization, with accompanying modifications in intramyocellular LD size and distribution, and diminished IRβ interaction with key regulatory proteins may be key contributors to impaired insulin‐mediated glucose uptake commonly found in adults with obesity.

Strenuous exercise training combined with erythropoietin (EPO) treatment increases blood volume, driven exclusively by red cell volume expansion. This hematological adaptation results in increased total oxygen-carrying capacity and hypervolemia. The marked upregulation of erythropoiesis with training + EPO reduces whole body iron stores and circulating hepcidin concentrations. The finding that the abundance of ferritin in muscle decreased after training + EPO suggests that muscle may release iron to support red blood cell production.

To examine factors underlying why most, but not all adults with obesity exhibit impaired insulin-mediated glucose uptake, we compared: 1) rates of fatty acid (FA) release from adipose tissue, 2) skeletal muscle lipid droplet (LD) characteristics, and 3) insulin signaling events in skeletal muscle collected from cohorts of adults with obesity with “HIGH” versus “LOW” insulin sensitivity for glucose uptake. Seventeen adults with obesity (BMI: 36±3kg/m ² ) completed a 2h hyperinsulinemic-euglycemic clamp with stable isotope tracer infusions to measure glucose rate of disappearance (glucose Rd) and FA rate of appearance (FA Ra). Skeletal muscle biopsies were collected at baseline and 30min into the insulin infusion. Participants were stratified into HIGH (n=7) and LOW (n=10) insulin sensitivity cohorts by their glucose Rd during the hyperinsulinemic clamp (LOW550 nmol/kgFFM/min/[µU/mL]). Insulin-mediated suppression of FA Ra was lower in LOW compared with HIGH (p<0.01). In skeletal muscle, total intramyocellular lipid content did not differ between cohorts. However, the size of LDs in the subsarcolemmal region (SS) of type II muscle fibers was larger in LOW compared with HIGH (p=0.01). Additionally, insulin receptor (IR) interactions with regulatory proteins CD36 and Fyn were lower in LOW versus HIGH (p<0.01), which aligned with attenuated insulin-mediated Tyr phosphorylation of IRβ and downstream insulin-signaling proteins in LOW. Collectively, reduced ability for insulin to suppress FA mobilization, with accompanying modifications in intramyocellular LD size and distribution, and diminished IR interaction with key regulatory proteins may be key contributors to impaired insulin-mediated glucose uptake commonly found in adults with obesity. KEY POINTS: Although most adults with obesity exhibit impaired insulin-mediated glucose uptake (insulin resistance), some remain sensitive to insulin. Factors that “protect” adults with obesity from developing resistance to insulin-mediated glucose uptake are poorly understood. Potent suppression of fatty acid (FA) mobilization from adipose tissue by insulin is a strong predictor of whole-body insulin-mediated glucose uptake. Participants with higher sensitivity for insulin-mediated glucose uptake had smaller intramyocellular lipid droplets (LDs) within the subsarcolemmal region of type II skeletal muscle fibers. Novel findings revealed that insulin receptor (IR) interaction with the long-chain fatty acid transport protein, CD36, and the Src-family kinase, Fyn, directly associated with higher rates of glucose uptake under basal and hyperinsulinemic conditions. Together, the findings suggest impaired suppression of FA release from adipose tissue associates with reduced glucose uptake in skeletal muscle due in part to a defect in IR activation by CD36/Fyn and altered subcellular LD characteristics.

In this study, 12 wk of either moderate-intensity continuous training (MICT) or high-intensity interval training (HIIT) enhanced skeletal muscle lipid abundance by increasing lipid droplet number within the intramyofibrillar (IMF) region of muscle. Because the IMF associates with high energy production during muscle contraction, this adaptation may enhance lipid oxidation during exercise. Despite differences in training intensity and energy expenditure between MICT and HIIT, their effects on muscle lipid abundance and metabolism were remarkably similar.

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