Decreased insulin‐stimulated brown adipose tissue glucose uptake after short‐term exercise training in healthy middle‐aged men

Abstract

Aims Little is known about the effects of exercise training on brown adipose tissue (BAT) metabolism in humans. We tested the hypothesis that high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) improve BAT insulin sensitivity. Materials and methods Healthy middle-aged men (n = 18, age 47 years [95% confidence interval {CI} 49, 43}, body mass index 25.3 kg/m2 [95% CI 24.1, 26.3], peak oxygen uptake (VO2peak) 34.8 mL/kg/min [95% CI 32.1, 37.4]) were recruited and randomized into six HIIT or MICT sessions within 2 weeks. Insulin-stimulated glucose uptake was measured using 2-[18F]fluoro-2-deoxy-D-glucose positron-emission tomography in BAT, skeletal muscle and abdominal and femoral subcutaneous and visceral white adipose tissue (WAT) depots before and after the training interventions. Results Training improved VO2peak (P=0.0005), insulin-stimulated glucose uptake into quadriceps femoris muscle (P=0.0009) and femoral subcutaneous white adipose tissue (P=0.02), but not into BAT, with no difference between the training modes. Using pre-intervention BAT glucose uptake, we next stratified subjects into high BAT (>2.9μmol/100g/min; n=6) or low BAT (<2.9 μmol/100g/min; n=12) groups. Interestingly, training decreased insulin-stimulated BAT glucose uptake in the high BAT group (4.0 [2.8, 5.5] vs. 2.5 [1.7, 3.6]) (training*BAT, P=0.02), whereas there was no effect of training in the low BAT group (1.5 [1.2, 1.9] vs. 1.6 [1.2, 2.0] μmol·100g·min−1). High BAT subjects had lower levels of inflammatory markers compared to low BAT subjects. Conclusions Subjects with functionally active BAT have an improved metabolic profile compared to subjects with low BAT activity. Short-term exercise training decreases insulin-stimulated BAT glucose uptake in subjects with active BAT, suggesting that training does not work as a potent stimulus for BAT activation.

Exercise counteracts the homeostatic decrease in thermogenesis caused by caloric restriction in sheep

“…Despite previous studies in rodents showing that exercise induces browning of white adipose tissue (18,19), this effect has not been established in larger mammals. In humans, exercise alone has little effect on the browning of white fat depots (20)(21)(22)36), and the present data in sheep are consistent with this. This is the first study in any species to indicate that exercise exerts beneficial effects on metabolism by counteracting the reduction in adaptive thermogenesis caused by food restriction.…”

Exercise-induced adaptations to white and brown adipose tissue

“…In humans, studies investigating the effects of exercise on BAT have only observed a decrease in BAT activity (Vosselman et al, 2015;Motiani et al, 2017). This does not mean that there are no exercise-induced adaptations to BAT; however, these data show exercise decreases cold-or insulin-stimulated glucose uptake in human BAT.…”

“…However, studies investigating the effects of exercise on BAT have yielded conflicting results (Stanford and Goodyear, 2016). In some studies, investigators have shown an increase in mitochondrial activity in rodent BAT (Ignacio et al, 2012;Yoshioka et al, 1989), whereas other studies have revealed a decrease in mitochondrial activity (Wu et al, 2014) and glucose uptake in BAT in exercise-trained humans (Vosselman et al, 2015;Motiani et al, 2017). Exercise has also been shown to affect the composition and concentration of phospholipids and triglycerides in the lipidome of rodent BAT (May et al, 2017).…”

“…3). A second study in humans looked at the effects of short-term exercise training, both high-intensity interval training and moderateintensity continuous training, on BAT metabolism in sedentary men using 2-[ 18 F]flouro-2-deoxy-D-glucose (FDG) and 14(R,S)-[ 18 F]fluoro-6-thia-heptadecanoic acid (FTHA) (Motiani et al, 2017). Twenty-eight healthy, middle-aged, sedentary men participated in the study.…”

Human brown adipose tissue as a target for obesity management; beyond cold‐induced thermogenesis

“…Conversely, while no human studies have definitively determined whether endurance training results in browning of adipose tissues, current evidence suggests the reverse. In a cross‐sectional study, young highly endurance trained males had lower cold‐stimulated BAT activity compared to a matched sedentary group and in a separate intervention study 2 weeks of training decreased insulin‐stimulated FDG uptake in previously untrained healthy men . Short‐term intense endurance training (10 d), also exerted no browning effect on human subcutaneous WAT in previously untrained young healthy males .…”