Molecular regulators of exercise-mediated insulin sensitivity in non-obese individuals

Insulin resistance is a significant contributor to the development of type 2 diabetes (T2D) and is associated with obesity, physical inactivity, and low maximal oxygen uptake. While intense and prolonged exercise may have negative effects, physical activity can have a positive influence on cellular metabolism and the immune system. Moderate exercise has been shown to reduce oxidative stress and improve antioxidant status, whereas intense exercise can increase oxidative stress in the short term. The impact of exercise on pro-inflammatory cytokine production is complex and varies depending on intensity and duration. Exercise can also counteract the harmful effects of ageing and inflamm-ageing. This review aims to examine the molecular pathways altered by exercise in non-obese individuals at higher risk of developing T2D, including glucose utilization, lipid metabolism, mitochondrial function, inflammation and oxidative stress, with the potential to improve insulin sensitivity. The focus is on understanding the potential benefits of exercise for improving insulin sensitivity and providing insights for future targeted interventions before onset of disease

The Metabolic Switch of Physical Activity in Non-Obese Insulin Resistant Individuals

Healthy non-obese insulin resistant (IR) individuals are at higher risk of metabolic syndrome. The metabolic signature of the increased risk was previously determined. Physical activity can lower the risk of insulin resistance, but the underlying metabolic pathways remain to be determined. In this study, the common and unique metabolic signatures of insulin sensitive (IS) and IR individuals in active and sedentary individuals were determined. Data from 305 young, aged 20–30, non-obese participants from Qatar biobank, were analyzed. The homeostatic model assessment of insulin resistance (HOMA-IR) and physical activity questionnaires were utilized to classify participants into four groups: Active Insulin Sensitive (ISA, n = 30), Active Insulin Resistant (IRA, n = 20), Sedentary Insulin Sensitive (ISS, n = 21) and Sedentary Insulin Resistant (SIR, n = 23). Differences in the levels of 1000 metabolites between insulin sensitive and insulin resistant individuals in both active and sedentary groups were compared using orthogonal partial least square discriminate analysis (OPLS-DA) and linear models. The study indicated significant differences in fatty acids between individuals with insulin sensitivity and insulin resistance who engaged in physical activity, including monohydroxy, dicarboxylate, medium and long chain, mono and polyunsaturated fatty acids. On the other hand, the sedentary group showed changes in carbohydrates, specifically glucose and pyruvate. Both groups exhibited alterations in 1-carboxyethylphenylalanine. The study revealed different metabolic signature in insulin resistant individuals depending on their physical activity status. Specifically, the active group showed changes in lipid metabolism, while the sedentary group showed alterations in glucose metabolism. These metabolic discrepancies demonstrate the beneficial impact of moderate physical activity on high risk insulin resistant healthy non-obese individuals by flipping their metabolic pathways from glucose based to fat based, ultimately leading to improved health outcomes. The results of this study carry significant implications for the prevention and treatment of metabolic syndrome in non-obese individuals.</p

Molecular regulators of exercise-mediated insulin sensitivity in non-obese individuals

Insulin resistance is a significant contributor to the development of type 2 diabetes (T2D) and is associated with obesity, physical inactivity, and low maximal oxygen uptake. While intense and prolonged exercise may have negative effects, physical activity can have a positive influence on cellular metabolism and the immune system. Moderate exercise has been shown to reduce oxidative stress and improve antioxidant status, whereas intense exercise can increase oxidative stress in the short term. The impact of exercise on pro-inflammatory cytokine production is complex and varies depending on intensity and duration. Exercise can also counteract the harmful effects of ageing and inflamm-ageing. This review aims to examine the molecular pathways altered by exercise in non-obese individuals at higher risk of developing T2D, including glucose utilization, lipid metabolism, mitochondrial function, inflammation and oxidative stress, with the potential to improve insulin sensitivity. The focus is on understanding the potential benefits of exercise for improving insulin sensitivity and providing insights for future targeted interventions before onset of disease.</p

Antioxidative Stress Metabolic Pathways in Moderately Active Individuals

Physical activity (PA) is known to have beneficial effects on health, primarily through its antioxidative stress properties. However, the specific metabolic pathways that underlie these effects are not fully understood. This study aimed to investigate the metabolic pathways that are involved in the protective effects of moderate PA in non-obese and healthy individuals. Data on 305 young, non-obese participants were obtained from the Qatar Biobank. The participants were classified as active or sedentary based on their self-reported PA levels. Plasma metabolomics data were collected and analyzed to identify differences in metabolic pathways between the two groups. The results showed that active participants had increased activation of antioxidative, stress-related pathways, including lysoplasmalogen, plasmalogen, phosphatidylcholine, vitamin A, and glutathione. Additionally, there were significant associations between glutathione metabolites and certain clinical traits, including bilirubin, uric acid, hemoglobin, and iron. This study provides new insights into the metabolic pathways that are involved in the protective effects of moderate PA in non-obese and healthy individuals. The findings may have implications for the development of new therapeutic strategies that target these pathways.</p

Antioxidative Stress Metabolic Pathways in Moderately Active Individuals

Physical activity (PA) is known to have beneficial effects on health, primarily through its antioxidative stress properties. However, the specific metabolic pathways that underlie these effects are not fully understood. This study aimed to investigate the metabolic pathways that are involved in the protective effects of moderate PA in non-obese and healthy individuals. Data on 305 young, non-obese participants were obtained from the Qatar Biobank. The participants were classified as active or sedentary based on their self-reported PA levels. Plasma metabolomics data were collected and analyzed to identify differences in metabolic pathways between the two groups. The results showed that active participants had increased activation of antioxidative, stress-related pathways, including lysoplasmalogen, plasmalogen, phosphatidylcholine, vitamin A, and glutathione. Additionally, there were significant associations between glutathione metabolites and certain clinical traits, including bilirubin, uric acid, hemoglobin, and iron. This study provides new insights into the metabolic pathways that are involved in the protective effects of moderate PA in non-obese and healthy individuals. The findings may have implications for the development of new therapeutic strategies that target these pathways

The Metabolic Switch of Physical Activity in Non-Obese Insulin Resistant Individuals

Healthy non-obese insulin resistant (IR) individuals are at higher risk of metabolic syndrome. The metabolic signature of the increased risk was previously determined. Physical activity can lower the risk of insulin resistance, but the underlying metabolic pathways remain to be determined. In this study, the common and unique metabolic signatures of insulin sensitive (IS) and IR individuals in active and sedentary individuals were determined. Data from 305 young, aged 20–30, non-obese participants from Qatar biobank, were analyzed. The homeostatic model assessment of insulin resistance (HOMA-IR) and physical activity questionnaires were utilized to classify participants into four groups: Active Insulin Sensitive (ISA, n = 30), Active Insulin Resistant (IRA, n = 20), Sedentary Insulin Sensitive (ISS, n = 21) and Sedentary Insulin Resistant (SIR, n = 23). Differences in the levels of 1000 metabolites between insulin sensitive and insulin resistant individuals in both active and sedentary groups were compared using orthogonal partial least square discriminate analysis (OPLS-DA) and linear models. The study indicated significant differences in fatty acids between individuals with insulin sensitivity and insulin resistance who engaged in physical activity, including monohydroxy, dicarboxylate, medium and long chain, mono and polyunsaturated fatty acids. On the other hand, the sedentary group showed changes in carbohydrates, specifically glucose and pyruvate. Both groups exhibited alterations in 1-carboxyethylphenylalanine. The study revealed different metabolic signature in insulin resistant individuals depending on their physical activity status. Specifically, the active group showed changes in lipid metabolism, while the sedentary group showed alterations in glucose metabolism. These metabolic discrepancies demonstrate the beneficial impact of moderate physical activity on high risk insulin resistant healthy non-obese individuals by flipping their metabolic pathways from glucose based to fat based, ultimately leading to improved health outcomes. The results of this study carry significant implications for the prevention and treatment of metabolic syndrome in non-obese individuals