Racial disparities in skeletal muscle: alternative approaches in glucose metabolism after exercise training in obese women of African ancestry

It is well recognized that obesity has a robust relationship to insulin resistance (IR) and the risk for developing metabolic disorders, such as type 2 diabetes and metabolic syndrome. Growing evidence indicates that the link between obesity and IR is largely explained by the pathological proliferation of fat cells, which results in an increased pro-inflammatory state. Chronic inflammation can stimulate the production of reactive oxygen species (ROS), which in turn leads to IR via increased activity of nuclear factor-κB and inhibition of the insulin receptor. At the same time, obesity induces mitochondrial dysfunction in adipose tissue culminating in an impaired balance between the production of ROS and antioxidant defences (oxidative stress). The interactive effect of inflammation and oxidative stress has therefore been proposed to be a key contributor to the obesity-induced IR (Nono Nankam et al. 2020). It is accepted that body fat distribution, rather than total fat mass, better predicts obesity-related complications. For example, compared to subcutaneous adipose tissue (SAT), visceral adipose tissue has a higher inflammatory profile and has been highly associated with IR. Importantly, the distribution of adipose tissue is influenced by ethnicity. Compared to white women, black African women have more gluteo-femoral and less visceral adipose tissue but experience minor sensitivity to insulin. This highlights the importance of considering ethnicity when studying the mechanisms and implications of adipose tissue distribution (Nono Nankam et al. 2020). Exercise training has long been known to cause adaptations to adipose tissue and prevent the development of metabolic disorders such as obesity, type 2 diabetes and metabolic syndrome. Exercise training exerts its therapeutic potential by decreasing adipocyte size, improving mitochondrial function, increasing the expression of key metabolic players such as glucose transporter type 4 (GLUT4) and peroxisome proliferator-activated receptor-γ coactivator 1α, and altering the secretion of adipokines, a group of cytokines secreted by adipose tissue that act in an autocrine/endocrine/paracrine manner to regulate inflammation and lipid and glucose metabolism (Stanford & Goodyear, 2018). However, the role of systemic/adipose tissue inflammation and oxidative stress in exercise training-induced improvements in black African women remains poorly explored. In a recent issue of The Journal of Physiology, Nono Nankam et al. (2020) reported the first randomized controlled trial that evaluates the effects of exercise training on systemic and SAT inflammation and oxidative stress in obese black African women. The intervention lasted 12 weeks and consisted of 40–60 min of combined aerobic (intensity: 75–80% peak heart rate) and resistance exercise training (intensity: 60–70% peak heart rate), performed 4 days per week. Following the intervention, cardio-respiratory capacity, body fat composition, insulin sensitivity (IS) and systemic oxidative stress improved in the exercise training group. Inflammatory markers increased in gluteal SAT, but remained unchanged in circulation and abdominal SAT. The authors suggested that the alterations in gluteal SAT inflammation were related to gynoid fat reduction as an adaptative response to exercise training-induced lipolysis, as recent evidence showed that increased adipose tissue remodelling – as occurs during exercise training – is followed by an increased local inflammatory state. Interestingly, changes in systemic ROS and inflammation in gluteal SAT were not associated with the improvement in IS, confirming that other mechanisms of insulin action are playing a more dominant role in this cohort (Nono Nankam et al. 2020). This review further discusses the findings reported by Nankam and colleagues by considering signalling between adipose and skeletal muscle (SM) tissue, racial-specific responses in insulin action and the effects of multiple exercise training modalities in insulin function. Visceral fat is strongly correlated to IR, while the gynoid fat mass distribution seems to be beneficial against obesity-related diseases, but contradictory findings have been described in black women. Despite the predominance of the gluteal fat depot, this population is less sensitive to insulin stimuli. Nono Nankam et al (2020) reported no changes in body fat mass and visceral adipose tissue in response to exercise training. Null correlations were found between reduction in gynoid fat mass and inflammatory changes in this depot with the improvements in IS after exercise training (Nono Nankam et al. 2020), supporting the idea that fat-independent mechanisms might be responsible for glucose metabolism in these women. Preclinical trials have shown that exercise training leads to paracrine/endocrine adaptations in adipose and muscle tissue. In 2015, Standford and colleagues transplanted SAT and perigonadal adipose tissue from trained mice in sedentary recipients. Only SAT-transplanted mice demonstrated advantages in glucose uptake, suggesting that exercise training produces biochemical shifts in adipose tissue according to its body distribution. Importantly, greater glucose uptake was found in oxidative fibres and brown adipose tissue in SAT-transplanted mice. Simultaneously, several studies have established the exercise training-induced release of myokines, proteins that may cause improvements in adipose tissue metabolic activity. Taken together, it is postulated that adipokines and myokines secreted by exercise training-adapted tissues (fat and SM, respectively) induce a ‘cross-talk’ between both tissues stimulating glucose uptake in oxidative fibres (Stanford & Goodyear, 2018). It is important to note that in the study of Nono Nankam et al. (2020) the measured adipokines, leptin and adiponectin were not altered by exercise training at both systemic and tissue levels. The authors associated these unexpected outcomes to an inadequate design of exercise training intervention and its poor effect on weight loss (Nono Nankam et al. 2020). Nevertheless, future research needs to contemplate an integral assessment of both components of the interrelation of fat–SM during exercise training to elucidate the pathways implicated in the insulin response. Higher incidence of IR and a doubled risk of type 2 diabetes have been reported in black women in comparison with their white counterparts. Dubé et al. (2020) assessed insulin efficiency in non-obese African-American women (AAW) and Caucasian women, showing similar hepatic IS but lower peripheral IS (26%) in AAW. Recently, the same research group revealed that a higher risk of IR in AAW was associated with specific mitochondrial characteristics in SM. This study recruited young, sedentary and lean participants; after a standard diet, a SM biopsy was taken for analyses of gene expression and protein content. Tissue analysis showed lower mitochondrial respiration rates mediated by six suppressed genes involved in fundamental pathways such as mitochondrial inner/outer membrane transport and autophagy in AAW. The mentioned racial disparities in mitochondrial pathways in SM were directly associated with IS, low metabolic rate, maximum oxygen uptake () and mitochondrial capacity. The exact mechanisms involved in these special SM characteristics remain unknown, although SM's structural and molecular attributes are relevant since mitochondrial function in muscle is strongly correlated with glucose uptake (Dubé et al. 2020). The physiological response to exercise training is to a large extent dependent on the frequency, type, duration and intensity of the exercise. Even though moderate-intensity exercise training has been shown to be effective in glycaemic control (Bird & Hawley, 2017), the results of Nono Nankam et al. (2020) showed that combined resistance and aerobic exercise training performed at moderate to vigorous intensity did not produce significant benefits on fasting glucose, fasting insulin and homeostatic model assessment of IR (HOMA2-IR) in obese black African women. According to the authors, the duration of the intervention was probably insufficient to observe significant modifications in biochemical markers (Nono Nankam et al. 2020). Importantly, the exercise training intensity may also have played a key role in the observed responses; when compared to moderate intensity, high-intensity exercise training induces greater benefits in glucose homeostasis. For example, high-intensity interval training (HIIT) – short and repetitive sessions of vigorous exercise training – showed greater improvements on IS, HOMA-IR and GLUT4 protein vs. continuous moderate-intensity exercise training in metabolically unstable individuals (Bird & Hawley, 2017). Notwithstanding, in black women, distinct outcomes have been detailed. Arad et al. (2015) conducted a randomized controlled trial of 14 weeks of HIIT (three sessions a week) in healthy sedentary and pre-menopausal overweight or obese AAW, where IS, body weight and peak oxygen uptake () remained unchanged, whereas exercise training tolerance and fat oxidation increased, and visceral adiposity volume declined. The researchers concluded that energy expenditure rather than intensity is a determinant exercise training component to induce significant changes in whole-body metabolism. However, in view of the positive effects generated by similar exercise training interventions in various populations, the absence of response in IS could be explained by the insulin infusion rate used in the study, which did not consider the differences in peripheral IS previously described in this ethnic group (Arad et al. 2015). The molecular bases of exercise training-induced improvements in IS of obese women of African ancestry remains unclear. On the basis of the evidence reviewed in this report, research needs to assume a key role of SM in IS including the interrelation between adipose and muscular tissue when implementing exercise training interventions and analysing their results. Future studies should explore and compare exercise training-mediated molecular pathways considering the ethnic characteristics of SM and the importance of its mitochondrial function when examining glycaemic control, inflammation and oxidative stress. None. Sole author. The author was supported by a CONACYT studentship from The Mexican National Council for Science and Technology. The author acknowledges Ever Espino Gonzalez, M.Sc., for his kind help and sincere cooperation in intellectual discussions.